CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells.

The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.

Bilateral Asymmetrical Fracture Dislocation of Shoulder with Rare Combination of Injuries after Epileptic Seizure: A Case Report.

The incidence of bilateral gleno-humeral joint dislocation is rare, is almost always posterior and is usually caused by sports injuries, epileptic seizures, electrical shock, or electroconvulsive therapy. Bilateral fracture-dislocation is even rarer, with a few cases reported in the literature. We report an unusual case with dislocation of the both glenohumeral joints in opposite direction after a seizure episode, with fracture of greater tuberosity on one side and of the lesser tuberosity on the contralateral side. Although there have been a few reports of bilateral asymmetric fracture dislocations of the shoulder in the past, an injury pattern resembling our case has, to the best of our knowledge, not been described in the literature so far. This report includes a detailed discussion regarding the mechanism of injury in a case of asymmetrical dislocation following a seizure episode. At final follow-up, the patient had healed fractures, painless near normal range of motion with no redislocations.

Neglected hip dislocation: an unusual presentation, its management and review of the literature.

Neglected traumatic posterior hip dislocation is not an uncommon condition seen in developing countries. Its treatment is fraught with great difficulties and controversies. Here we present a 31-year-old female patient presented to our hospital 2 years after sustaining an accident. She had gone through multiple treatments for her dislocated hip without any success. After arrival to our hospital, patient managed by constrained total hip replacement (THR). Her Harris hip score improved from 48 (preoperative) to 81 (postoperative). On follow-up she had a good range of movement of the hip with no pain, deformity and limb length discrepancy. Constrained THR provides promising results in neglected hip dislocation.

Effect of l-Arginine on Nitric Oxide Levels in Intrauterine Growth Restriction and its Correlation with Fetal Outcome.

The current management of intrauterine growth restriction (IUGR) being empirical and aimed at selecting a safe time for delivery. Acknowledging the beneficial effects of l-arginine on endothelial vasculature the present study was designed to evaluate efficacy of l-arginine on bioavailability of nitric oxide (NO) with respect to fetal outcome. With l-arginine supplementation, mean NO levels were significantly increased and a significant mild reduction in systolic/end-diastolic velocity ratio (S/D ratio) was observed on doppler blood flow study, also neonatal outcome improved and incidences of complications were lowered. A deficiency in NO may play an important role in the causation of asymmetric fetal growth restriction. l-Arginine can be used to increase maternal NO levels, enhancing birth weight and decreasing neonatal morbidity. The ideal candidate for arginine therapy according to our study would be IUGR cases with S/D ratio less than 4.96 ± 0.49 and NO levels below 33 µmol/L with minimum of 3 weeks duration of arginine supplementation.

Pleuropulmonary blastoma.

Pleuropulmonary blastoma is a rare and aggressive malignant tumour that affects young children. A case of pleuropulmonary blastoma has been presented in a 9-year-old male child who was initially diagnosed and treated as pulmonary tuberculosis. Computed tomography of chest revealed a large heterogeneously enhancing mass with calcification in left hemithorax and left pleural effusion. The mass was seen to invade mediastinum and left hemidiaphragm. Thoracotomy revealed unresectable tumour involving both lobes of left lung with invasion of mediastinum and left hemidiaphragm. Biopsy confirmed type II pleuropulmonary blastoma and the child was treated with chemotherapy and radiotherapy.

Extraosseous Ewing's sarcoma / primitive neuroectodermal tumor of the sacral nerve plexus.

We report an unusual case of Ewing's sarcoma / primitive neuroectodermal tumor (PNET) of the sacral nerve plexus in a 9-year-old boy who presented with a soft tissue swelling and severe piercing pain in the lower back region. MRI of the lumbosacral spine showed a lobulated soft tissue mass with clubbed finger-like projections along the path of the sacral nerves, which had caused widening of the spinal canal and the sacral foramina (S2-S4 level). There was presacral extension and posterior scalloping of the sacral vertebrae. Histopathology of the lesion confirmed Ewing's sarcoma / PNET of the sacral spinal nerve plexus. The patient responded favorably to chemotherapy and radiotherapy, showing clinical and radiological improvement.

Status of lipid peroxidation and plasma iron level in bronchial asthmatic patients.

Low antioxidant levels and oxidative stress due to airway inflammation may be determinant of asthma severity. The study was conducted to find the extent of lipid peroxidation and change in the levels of plasma iron in asthmatic patients with severity of disease. Study included 155 asthmatic and 156 healthy volunteers of the age groups 18-45 of either sex. Asthmatic patients were grouped into mild, moderate and severe groups on the basis of Forced Expiratory Volume in first second percent (FEV1%). Level of plasma malondialdhyde (MDA) was used as index of lipid peroxidation. A significant increase (P<0.01) in plasma MDA and plasma iron levels was found in asthmatic subjects as compared to controls. There was maximum increase in plasma MDA and iron levels in moderate asthmatic group. A positive correlation between plasma MDA and iron (r = +0.3) has been found in asthmatic patients. An increased plasma iron levels in asthmatics may contribute to aggravate lipid peroxidation.

Diabetes mellitus in an infant.

Onset of diabetes in the first year of life is uncommon, most cases being those of transient diabetes of the newborn. We report the case of a child who presented at 10 weeks of age with diabetic keto-acidosis, and continues to be insulin dependent at 18 months.

Leber's amaurosis with nephronophthisis and congenital hepatic fibrosis.

We describe a case of Leber's amaurosis in a one-year-old girl with unusual presentations. She presented with small clue like tachypnea and nystagmoid novement of eyeswhich when pursued revealed involvement like hepatic, renal and retina.

Imaging and morphology of the paracondylar process in a dry adult human skull: a case report.

An unusually long paracondylar process (PCP) was found articulating with the transverse atlantal process in a dry adult male skull. It was 13 mm long and 19 mm in circumference at its middle and projected to a lower plane than the styloid process of the same side. A radiograph revealed the structure of spongiosa of the PCP to be like mastoid cells. PCP can lead to clinical symptoms due to alterations in posture and functional limitations in neck movements. Thus awareness of this process, its topographical relations and its attendant problems is of importance to clinicians, radiologists, surgeons and chiropractors. In symptomatic cases surgical resection of this process can be attempted to relieve the symptoms. The craniovertebral junction constitutes a unique part of the somite-derived axial skeleton; the lowest part of the basioccipital component including this process develops from occipital sclerotomes. Developmental variations in this region can resemble deformities.

Ultrasonographic assessment of thyroid volume in Delhi children.

BACKGROUND: Ultrasonographic measurement of thyroid volume is increasingly being used to assess prevalence of iodine deficiency in a community. OBJECTIVES: To assess thyroid volume by ultrasonography in normal Delhi children, and compare them with the recently adopted WHO reference standards. METHODS: One hundred and three children aged of 6-10 years were enrolled from the paediatric outpatient clinic in a prospective study. Thyroid volume was estimated by ultrasound, and urinary iodine levels were measured for all subjects by spot urine samples. RESULTS: Goitre prevalence was 24.3% on clinical assessment. Urinary iodine levels fell in the range of mild to moderate deficiency in 61% of the children. None of the children met the WHO recommended ultrasonographic criteria for goitre (thyroid volume >97th percentile of the reference standards), when WHO age-specific norms were used for comparison. On applying body surface area (BSA)-specific norms, only two children were classified as having goitre. CONCLUSIONS: The WHO standards for thyroid volume by ultrasonography tended to underestimate goitre prevalence.

Fine-needle aspiration diagnosis of giant cell tumour of bone presenting at unusual sites.

Giant cell tumour (GCT) of bone is a distinctive neoplasm, which has only recently been included within the diagnostic purview of the cytopathologist. Four cases of GCT of bone diagnosed primarily and exclusively by fine needle aspiration cytology (FNAC), presenting at unusual sites, are presented with a view to highlight the cytomorphologic features of this tumour and its differential diagnosis on FNAC. Each of these cases were distinctive by virtue of their localisation, but presented as classical expansile osteolytic lesions roentgenologically. Despite the paucity of literature regarding the cytodiagnosis of these lesions, the authors nevertheless recommend FNAC as a primary tool in the diagnosis of these lesions.

Lipid peroxidation in haemorrhagic shock and after transfusion of blood in dogs.

The present study was carried out on mongrel dogs. Haemorrhagic shock of different severities and duration was produced by exsanguination from an artery. After the required duration of shock, two third of the volume of blood withdrawn was transfused back into the animal. Effect of haemorrhage and reperfusion of blood after haemorrhagic shock on lipid peroxidation was assessed by measuring plasma malondialdehyde (MDA). Severity of shock was assessed from the haematocrit values. There was a significant increase (P < 0.05) in plasma MDA level after blood transfusion in a group having 40 mm Hg blood pressure as magnitude of shock and one hour as duration of shock (Group II) only. Haemotocrit value was also significantly low (P < 0.05) in this group after haemorrhagic shock. Results are suggestive of lipid peroxidation with ischaemic reperfusion in severe and long duration of shock.

International HIV and AIDS prevention: Japan/United States collaboration.

As the epicenter of the HIV/AIDS pandemic shifts from Africa to Asia, Japan is becoming ever more aware of the importance of containing and preventing spread of the virus. International collaboration, particularly with the United States, is a logical approach because it allows utilization of expertise from countries in other stages of the pandemic, can prevent duplication of efforts, and complements efforts of the other countries. Further, both Japan and the United States can use their combined influence and prestige to encourage cooperation among all nations. In 1994, Japan established the Global Issues Initiative to extend cooperation to developing countries in the areas of population and AIDS control. It has disbursed more than $460 million (U.S.$) to promote active cooperation and stimulate international attention to the importance of addressing these health issues. Japan has established four main programs for international collaboration for control of HIV and AIDS, three operated by ministries and one by a Japanese nongovernmental organization. Japanese/United States collaboration is developing through the United States/Japan Cooperative Medical Sciences Program, the Common Agenda for Cooperation in Global Perspective, the Paris Summit, and the United Nations Joint Programme on AIDS. It is critical that Japan and the United States, as the two largest donors to international development, demonstrate, through their collaboration, ways to maximize the use of limited resources, reduce duplication, and promote sustainable development programs in which HIV prevention and AIDS care programs are systemically integrated.

Papillary cystic neoplasm of the pancreas, diagnosed by fine needle aspiration cytology--a case report.

A case of papillary cystic neoplasm of the pancreas diagnosed by fine needle aspiration cytology is presented surgical removal of the pancreatic tumour and histological study confirmed the cytologic diagnosis. A brief review of the literature and emphasis on cytological and histological features are discussed.

HIV-related tuberculosis in England and Wales.

Numbers of tuberculosis notifications in England and Wales increased by 8% from 1987 to 1989. An analysis of notifications by age and sex has been undertaken to determine whether this increase has been due to an increase in young male adults, as has occurred in the USA, implying that HIV is largely responsible for the increase in notifications. Though notifications increased by 9.5% in younger males between 1987 and 1989 they also increased by over 10% amongst most age groups of females, and elderly males. These findings would suggest that there are a number of factors causing a rise in tuberculosis notifications, and that HIV is not yet directly implicated in England and Wales.