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.     

Reciprocal effect of Waardenburg syndrome mutations on DNA binding by the Pax-3 paired domain and homeodomain

The Pax-3 protein contains two DNA-binding domains, a paired domain and a homeodomain. Mutations in Pax-3 cause Waardenburg syndrome (WS) in humans and the mouse Splotch (Sp) phenotype. In the Sp-delayed mouse, a mutation in the Pax-3 paired domain (G9R) abrogates the DNA-binding activity of both the paired domain and the homeodomain, suggesting that they may functionally interact. To investigate this possibility further, we have analyzed the DNA-binding properties of additional point mutants in the Pax-3 paired domain and homeodomain that occur in WS patients (F12L, N14H, G15S, P17L, R23L, G48A, S51F and G66D in the paired domain, V47F and R53G in the homeodomain), the Pax-1 un mutation (G15A) and a substitution associated with Peters' anomaly in the PAX-6 gene (R23G). Within the paired domain, seven of 10 mutations were found to abrogate DNA-binding by the paired domain. Remarkably, these seven mutations also affected DNA binding by the homeodomain, causing either a complete loss (P17L and G66D), a reduction (R23G, R23L, G15S and G15A) or an increase in DNA-binding activity (N14H). In addition, the effect of paired domain mutations occurred at the level of monomer formation by the homeodomain, while the dimerization potential of this domain seemed unaffected in mutants where it could be analyzed. Furthermore, while both homeodomain mutations were found to abolish DNA binding by this domain, the R53G mutation also abrogated DNA binding by the paired domain. The important observation that independent mutations in either domain can affect DNA binding by the other in the intact Pax- 3 protein strongly suggests that the two domains are not functionally independent but bind DNA through cooperative interactions. Modeling the deleterlous mutations on the three-dimensional structure of the paired domain of Drosophila Prd shows that these mutations cluster at the DNA interface, thus suggesting that a series of DNA contacts are essential for DNA binding by both the paired domain and the homeodomain of Pax-3.      

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.     

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population. BACKGROUND: More than 285,000 individuals in the United States suffer from end-stage renal disease (ESRD) and are treated predominantly by dialysis. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are few data about the level of renal function at the onset of ESRD and no established medical criteria for the initiation of dialysis. METHODS: We report the level of serum creatinine and glomerular filtration rate (GFR) in 90,897 patients who began dialysis in the U. S. between April 1995 through September 1997. Data were obtained from the U.S. Renal Data System. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. RESULTS: The mean (SD) serum creatinine was 8.5 (3.8) mg/dl. The mean (SD) predicted GFR was 7.1 (3.1) ml/min/1.73 m2, with a range from 1 to 42 ml/min/1.73 m2. The proportion of patients with predicted GFR of > 10, 5 to 10, and <5 ml/min/1.73 m2 was 14, 63, and 23%, respectively. The mean predicted GFR was significantly lower among younger patients, women, African Americans, patients with a higher body weight, patients with ESRD because of diseases other than diabetes, uninsured patients, patients who were employed, homemakers or students, and patients selecting hemodialysis. CONCLUSIONS: There is wide variation in renal function at the initiation of dialysis in the U.S. ESRD population, and a substantial fraction of patients start dialysis at very low levels of predicted GFR. Further analyses are needed to examine the factors associated with late initiation of dialysis and its impact on the cost and outcomes of ESRD.     

Prediction of walking possibility in crawling children in poliomyelitis

Crawling is one of the most common modes of ambulating in children with severe paralysis and deformities in poliomyelitis. Restoring upright posture and bipedal gait, although desirable, has its own limitations due to various factors. Fifty-three children below the age of 12 years (29 boys and 24 girls) crawling due to post-poliomyelitis residual paralysis were assessed for the genesis of crawling as a mode of ambulating. The patterns of crawling were classified according to Cross's classification. Paralyzed muscles and deformities in definite combinations were found responsible for each type of crawling. Trunk muscles, gluteus maximus, quadriceps, hamstrings, tibialis anterior, and triceps surae were identified as muscles crucial for walking in order of priority. At least antigravity power in these muscles was necessary for an upright posture and walking with support. Various combinations of treatment modalities were used to correct the deformities before fitting an orthosis and instituting gait training. Thirty-four children became outdoor walkers, 14 indoor walkers, and five remained nonwalkers. The most favorable patterns of crawling for restoration of upright posture were true quadruped progression (30 cases) and infant-like crawl (14 cases). Average follow-up was 17 months (range, 6 months to 5 years).     

PREVALENCE OF MICROALBUMINURIA IN NON-INSULIN-DEPENDENT DIABETES MELLITUS

The prevalence of microalbuminuria was assessed in 50 patients of non-insulin dependent diabetes mellitus. The mean age of patients was 52.1 ± 11.6 years and the duration of diabetes was 8.3 ± 6.8 years. Twenty (40%) patients had microalbuminuria. Microalbuminuria was more common in patients with a longer duration of diabetes (more than 5 years), a poor glycaemic control, and higher systolic blood pressure.KEY WORDS: Microalbuminuria, Diabetes mellitus, Diabetic nephropathy, Chronic renal failure     

Effect of oral contraceptives on urinary porphyrins

Several studies have reported on the appearance of cutaneous porphyria in people treated with estrogen. This study was undertaken to investigate the effects of oral contraceptives (OCs) on levels of porphyrins in urine in nonporphyric women. 30 women aged 21-40 and on OCs were observed as the study group, and 10 women using other contraceptive methods were observed as the control group. Urinary porphyrins were measured by the Remington method. Levels of urinary coproporphyrin and of urinary uroporphyrin were higher in the study group than in the control group. These differences, however, are not statistically significant. To study the effect of duration of OC treatment, women who had taken OCs for 3-6 months and women who had taken OCs for longer than 6 months were observed, and the means of urinary coproporphyrin and uroporphyrin measured. Again, the differences were found to be insignificant, although slightly higher values of urinary coproporphyrin were obtained for women who had been on OCs for a longer period. These results compare favorably with others reported in the published literature. It can be concluded that OC treatment has no significant bearing on porphyrin metabolism.     

Self-administered mixture of Entonox and isoflurane in labour

Entonox (50% nitrous oxide premixed in oxygen) was compared with a mixture of Entonox and approximately 0.25% isoflurane (Entonox-isoflurane) for pain relief in the first stage of labour in 39 mothers. An Oxford Miniature Vaporizer was incorporated as the draw-over vaporizer for adding isoflurane to Entonox. The mixture was self-administered via the Entonox on-demand valve. The two mixtures were given in random sequence for five consecutive contractions of labour to each patient. Linear analogue pain relief scores were significantly higher (P=0.001) with Entonox-isoflurane. Fourteen patients continued using Entonox-isoflurane until delivery. No adverse effect from prolonged use was noted. Entonox-isoflurane is considered worthy of further investigation.