Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. However, many patients lack suitable HLA- matched related donors and must rely on unmatched donors for a source of stem cells. The purpose of this study was to evaluate outcomes of unrelated donor umbilical cord blood transplantation after chemotherapy-based myeloablative conditioning and retrospectively determine if baseline studies correlate and help predict outcome. Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who lacked HL- matched related donors were referred to Duke University Medical Center for transplantation. These children were conditioned with myeloablative therapy including busulfan, cyclophosphamide, and antithymocyte globulin before receiving umbilical cord-blood transplants from unrelated donors. Baseline studies of neurophysiologic, neuroimaging, and neurodevelopmental status were performed and patients were subsequently evaluated for survival, engraftment, graft-versus-host disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline neuroimaging and neurophysiologic studies correlated with cognitive and motor function and if these studies were predictive of posttransplantation outcomes. The umbilical cord blood grafts had normal levels of very long chain fatty acids. They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil engraftment occurred at a median of 22.9 days after transplantation. Three patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic graft-versus-host disease. Cumulative incidence of overall survival of the group at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was 3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow transplantation, symptomatic patients faired poorly with lower survival and rapid deterioration of neurologic function. This study included 3 patients transplanted at a very young age (2.6-3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3-5 years posttransplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiologic studies failed to show statistically significant differences. Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.     

Food allergies--leads from Ayurveda

Food allergy being a common health problem needs attention. The experience of Ayurveda can be utilized to accelerate our understanding and management of food allergies and related phenomenon like allergic tension fatigue syndrome, intolerance and indigestion associated with certain foods. Prevention of food allergies by carefully selecting the foods in accordance with the individual's body constitution and seasonal alterations, is considered as the best strategy in Ayurveda. If possible, the concept of prakriti and properties of food as described in Ayurveda, should be interpreted in modern terminology. Moreover, to scientifically validate them, an appropriate correlation with modern concepts is required along with scientific studies on modern parameters. Rasayanas may also prove helpful in the management of food allergies. It is obvious that there, is an urgent need for multidimensional and planned investigations of these Ayurvedic rasayanas in management of food allergies. The clinical acceptability of rasayanas for the treatment of food allergies entirely rests on such studies. Food intolerance and allergies are common health problems which are difficult to diagnose and still more difficult to treat. This problem is well addressed in Ayurveda and guidelines are available for their management. This paper aims to present the Ayurvedic concepts in the management of food intolerance/ allergies and its correlation with the evidences available from modem scientific laboratories. The understanding of this ancient wisdom may prove to be of immense importance in patient care.     

Extraskeletal chondroma of the hand--a case report

Extraskeletal chondroma is a rare entity. A fairly benign condition, it is usually seen in adults. It presents as an enlarging mass, most commonly in the hand. Local excision is the treatment of choice. We present a case of extraskeletal chondroma of hand in a 12 year male child. Its variable histological appearance not infrequently leads to a mistaken diagnosis of chondrosarcoma.     

Immunochemical characterization of cocos nucifera pollen

The Cocos nucifera pollen, as one of the sources of allergen responsible for immediate hypersensitivity reaction, was confirmed by skin prick test, bronchial provocation test, and RAST. The whole pollen extract (WPE) of C. nucifera was fractionated by combination of gel filtration and ion-exchange columns with fast protein liquid chromatography (Pharmacia, Uppsala, Sweden). Three protein peaks designated Cocos II, Cocos VI, and Cocos VII exhibited allergenic properties, as tested by skin prick test, direct IgE ELISA, bronchial provocation test, and immunoblot analysis. In RAST inhibition, Cocos IIa (a high-molecular-weight protein) obtained by fractionation of Cocos II on Mono Q column (fast protein liquid chromatography) (Pharmacia) was found to be the most potent allergen in Cocos WPE, followed by Cocos VI and Cocos VII, which are low-molecular-weight proteins. The reference patterns of Cocos WPE on crossed immunoelectrophoresis and thin-layer isoelectric focusing were established for future standardization of Cocos WPE to be used in the diagnosis and immunotherapy of allergic patients.     

Aspiration cytology diagnosis of a primary amyloid tumor of thoracic vertebra: a case report

Isolated primary amyloid tumor of bone is rare; however, preoperative diagnosis can be rewarding because the prognosis is excellent. There are no clinical or roentgenographic criteria that can establish this diagnosis. There are few previous reports of fine-needle aspiration (FNA) where diagnosis of amyloidoma was made retrospectively. They describe the presence of extracellular hyaline material along with plasma cells and lymphocytes. A 35-year-old female was referred to the FNA clinic with swelling in the right upper chest wall. Radiologic findings revealed a destructive lytic lesion involving the bodies of D1 and D2 vertebrae with extension into surrounding soft tissue. Repeated FNA smears were hypocellular but had abundant homogeneous flocculent material, which stained positive with Congo red. A few plasma cells and foreign-body giant cells were also seen. We conclude that preoperative FNA cytology diagnosis of amyloid tumor is possible. Hypocellular smears with flocculent material, plasma cells, and foreign-body giant cells in absence of granulation tissue should suggest the diagnosis.     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

A study on antigenic and allergenic changes during storage in three different biological extracts.

The stability of three allergens common in tropical countries was evaluated under different storage conditions. Prosopis juliflora (PJ), Rhizopus nigricans (RN), and wheat dust (WD), were taken as representatives of various groups of allergens viz, pollen, fungi and dust. The extracts were stored in buffer containing phenol (0.4%) or glycerol (50%) at temperatures ranging from 4-55 degrees C for 15 to 60 days. Protein content of PJ extract was reduced remarkably when it was stored at 40 degrees C for 45 days. Thin layer isoelectric focusing and rocket immunoelectrophoresis of PJ showed that certain antigenic proteins degrade rapidly even at 25 degrees C as early as day 15. However, two to three proteins of PJ remain stable at a higher temperature (40 degrees C) for two months. Relative radioallergosorbent test (RAST) inhibition showed substantial loss of allergenic activity in all the three extracts, when stored at higher temperatures (25-55 degrees C) even for short durations, i.e., 15 days. Extracts (PJ and RN) containing 50% glycerol were found to be stable, retaining more than 50% activity, even when stored at 55 degrees C for 40 days, while extracts without glycerol lost more than 75% of their allergenic activity. However, addition of glycerol did not change the stability of wheat dust allergenic extract. The present findings indicate that allergenic extracts behave differently when stored. Hence, the stability of each extract should be determined individually.     

Immune regulation during allergic bronchopulmonary mycosis

Allergic bronchopulmonary mycosis (ABPM) is a devastating pulmonary disease that results from an aggressive allergic response to fungal colonization in the airways. Animal models using either fungal antigen or live infection reproduce most of the clinical features seen during ABPM in humans. Results from these studies have facilitated a detailed analysis of the key factors involved in the afferent as well as efferent phase of the disease. This review focuses on allergic bronchopulmonary disease caused by two different fungi (Aspergillus fumigatus and Cryptococcus neoformans): allergic bronchopulmonary aspergillosis and allergic bronchopulmonary cryptococcosis. Observations from both models underline the importance of initial innate immune responses and their translation into appropriate adaptive responses. In addition, data derived from knockout studies give emphasis to targeting cytokines and chemokines as a therapeutic strategy in the treatment of ABPM.     

Medicaid managed care in Iowa: Experiences of older adults and people with disabilities

BackgroundA growing number of states are turning to managed care arrangements to provide care to senior and disabled Medicaid beneficiaries. Despite their complex care needs, very little is known about the experience of these individuals in managed care.ObjectiveTo document experiences of a sample of aged and disabled Medicaid beneficiaries receiving long-term services and supports through managed care in Iowa and to assess whether these experiences changed over time.MethodsA purposive sample of 49 aged and disabled beneficiaries enrolled in one of seven HCBS waivers in Iowa was recruited in 2017. Telephone surveys were conducted in 2017 and 2019. A conventional content analysis was used to generate themes, which were then ranked by frequency proportions. Thematic frequencies were compared across waves among repeat respondents.ResultsContent analysis yielded seven themes in the following areas: system navigation; service approvals; provider relations; customer service; case management; perception of Iowa’s transition to managed care; and oversight. Concerns with service approvals was the most frequently reported theme and within this, issues related to changes in approved services or hours and quality of newly approved services comprised the largest number of references. Beneficiary concerns appeared to grow over time among respondents participating in both survey interview waves.ConclusionThe results of this study point to serious and persistent concerns related to access and quality of care under managed care for at least some HCBS waiver participants in Iowa, underscoring the need for a comprehensive evaluation of the program.