Can Sensitized Lymphocytes Retain Reactivity to Inner Ear Antigens After Retrieval From Frozen Storage?

Immune inner ear disease results in rapidly progressive, bilateral sensorineural hearing loss and is one of the few forms of sensorineural hearing loss that can be treated medically. The purpose of this study is to identify and preserve several populations of sensitized lymphocytes from patients with immune inner ear disease as a first step toward cloning autoreactive T cells, in order to study the pathogenesis of disease. Lymphocytes from four patients with high reactivity (stimulation index of 2.5 or greater) were placed in frozen storage. At 8 to 14 months they were thawed and restimulated. All four samples were viable. Two reacted again to inner ear homogenate, but with different intensities. Some lymphocytes sensitized to inner ear antigens can retain reactivity after frozen storage. This methodology may be useful to clone highly reactive T cells.     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)     

Development of a Pacifier for Low-Birth-Weight Infants' Nonnutritive Sucking

Nonnutritive sucking can provide low-birth-weight infants with an opportunity to organize their behavior, an important component of developmental care. A pacifier specifically designed for low-birth-weight infants facilitates their nonnutritive sucking to more fully meet their needs. The research and development of a pacifier for low-birth-weight infants incorporated a naturalistic approach and used the best model, the infant thumb, in the design. Clinical trials with infants randomized to control and experimental groups were conducted to compare the prototype pacifier to a commercially available pacifier. Observations using the Anderson Behavioral State Scale demonstrated that infants using the prototype pacifier more often were found to be in an alert state. This pacifier may contribute to infants' state organization for optimum feeding and could be a component in developmental care planning.     

Dietary factors and cancers of breast, endometrium, and ovary: Strategies for modifying fat intake in African American women

Modification of dietary fat and fiber could help prevent cancers of the breast, endometrium, and ovary that are prevalent in African-American women. Dietary intervention programs aimed at reducing fat intake have had mixed results in this population. The transtheoretic model is proposed for achieving dietary change. Strategies for changing health behaviors in African-American women include heightening sensitivity to cultural values among health educators and the use of multiple strategies to reinforce messages. To stimulate healthier eating, it is important to incorporate the distinct habitual eating patterns into innovative intervention methods, using effective behavioral change methods. (Am J Obstet Gynecol 1997;176:S255-64.)     

Pharmacokinetics of trofosfamide and its dechloroethylated metabolites

 To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years who were treated with 150 or 250 mg/m² Trofo in combination with etoposide. Serum samples were collected with 13 patients after oral administration, and Trofo and its dechloroethylated metabolites were quantified by gas chromatography. Urine samples were collected from five patients and analyzed by same method. Ifosfamide (Ifo) was the main metabolite in serum and urine (AUC_Trofo:AUC_Ifo 1:13), whereas cyclophosphamide (Cyclo) was formed in smaller amounts (AUC_Ifo:AUC_Cyclo 18:1). Ifo and Cyclo were further oxidized in the chloroethyl side chains to form 2- and 3-dechloroethylifosfamide in varying quantities. The urinary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose. Our results confirm former in vitro observations about the metabolism of Trofo. The main side-chain metabolites Ifo and Cyclo can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an interesting agent for oral chemotherapy. Received 21 July 1996 / Accepted: 11 November 1996