Acoustic variations in reading produced by speakers with spasmodic dysphonia pre-botox injection and within early stages of post-botox injection.

Acoustic analysis of a reading passage was used to identify the abnormal phonatory events associated with adductor spasmodic dysphonia (ADSD) pre- and postinjection of Botulinum Toxin A (Botox). Thirty-one patients (age 22 to 74 years) diagnosed with ADSD were included for study. All patients were new recipients of Botox, and the examination of their voice occurred before and after their initial injection of Botox. Acoustic events were identified from reading samples of the Rainbow Passage produced by each of the patients. These events were examined from sentences containing primarily voiced sound segments. Dependent variables included the number of phonatory breaks, frequency shifts, and aperiodic segments--all variables previously defined by the investigators. Additionally, calculated variables were made of the percentage of time these events occurred relative to the duration of the cumulative voiced segments. A sex- and age-matched control group (+/-2 years) was included for statistical comparison. Results indicated that those with ADSD produced more aberrant acoustic events than the controls. Aperiodicity was the predominant acoustic event produced during the reading, followed by frequency shifts and phonatory breaks. Within the ADSD group, the number of atypical acoustic events decreased following Botox injection. It is important that the occurrence of specific abnormal acoustic events was sufficient to differentiate the disordered speakers from the controls following as well as preceding initial Botox injection, as indicated by discriminant function analysis. This paper complements our previous work using this acoustic analysis method for defining the abnormal events present in the voice of those with ADSD and further suggests that these measures can be used in conjunction with perceptual impressions to differentiate speakers on the basis of initial severity.     

The influence of protein solubilisation, conformation and size on the burst release from poly(lactide-co-glycolide) microspheres.

Encapsulation of proteins in poly(lactide-co-glycolide) microspheres via emulsion is known to cause insoluble protein aggregates. Following protein emulsification and encapsulation in PLGA microspheres, we used circular dichroism to show that the recoverable soluble protein fraction also suffers subtle conformational changes. For a panel of proteins selected on the basis of molecular size and structural class, conformational stability measured by chemical denaturation was not indicative of stability during emulsion-encapsulation. Partial loss of structure was observed for alpha-helical proteins released from freeze-dried microspheres in aqueous buffer, with dramatic loss of structure for a beta-sandwich protein. The addition of sucrose (a lyoprotectant) did not prevent the loss of protein conformation upon encapsulation. Therefore, the conformational changes seen for the released soluble protein fraction originates during emulsification rather than microsphere freeze-drying. Analysis of the burst release for all proteins in buffer containing denaturant or surfactant showed that the degree of protein solubilisation was the dominant factor in determining the initial rate and extent of release. Our data for protein release into increasing concentrations of denaturing buffer suggest that the emulsion-denatured protein fraction remains insoluble; this fraction may represent the protein loss encountered upon comparison of protein encapsulated versus protein released.     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

Factors causing interrupted delivery of enteral nutrition in trauma intensive care unit patients.

BACKGROUND: The intent of this study was to ascertain the adequacy of delivery of enteral nutrition (EN) to critically ill adult multiple trauma patients and to identify potential detrimental factors that affect EN delivery. METHODS: Retrospective observational study. Trauma intensive care unit (TICU) in a university-affiliated hospital. Adult patients (>/=18 years of age) admitted to the TICU who received enteral feeding. RESULTS: Fifty-six adult patients were enrolled for study. Patients received, on average, 67% +/- 19% of what was prescribed for 5.7 +/- 2.0 days. A total of 222 occurrences for temporary discontinuation of tube feeding were identified. Gastrointestinal intolerance, as defined by a gastric residual volume of >150 mL, abdominal pain, or >3 liquid stools per day, accounted for only 11% of the occurrences for discontinuation of feeding. Surgery (27%) and diagnostic procedures (15%) represented the majority of reasons for inadequate nutrient delivery. Minor factors for EN interruptions were mechanical feeding tube problems (8%), pharmacy delivery delay (4%), and miscellaneous factors (3%). Multiple and unknown reasons contributed to 14% and 18% of the occurrences, respectively. CONCLUSIONS: Surgery and diagnostic procedures accounted for the largest factor in enteral feeding discontinuations in our critically ill trauma patients. Gastrointestinal intolerance contributed a minor role in the temporary discontinuation of enteral feeding.     

Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.     

Local induction of an insulin-like growth factor binding protein-3 degrading protease activity in the course of wound healing

Proteases that reduce insulin-like growth factor binding protein-3 affinity for insulin-like growth factor-I have been found in various biological fluids from human beings and rats. The aim of this study was to assess the local and systemic role of insulin-like growth factor binding protein-3 proteases in the course of wound healing. Six rats had polyvinyl alcohol sponges implanted subcutaneously. Wound fluid and serum were collected 3 days after wounding. Gel filtration experiments showed that insulin-like growth factor-I was present as a 150 kDa complex in both serum and wound fluid. However, insulin-like growth factor binding protein-3 measured by Western ligand blotting was virtually absent in wound fluid. Co-incubation of serum and wound fluid resulted in an ethylenediamine tetraacetic acid-inhibitable degradation of serum insulin-like growth factor binding protein-3, suggesting the presence of an insulin-like growth factor binding protein-3 degrading activity in wound fluid. Incubation of ((125)I)-labeled insulin-like growth factor binding protein-3 in wound fluid and serum showed a rapid and time-dependent proteolysis of insulin-like growth factor binding protein-3 in wound fluid with metabolites similar to those generated by human term pregnant serum. No sign of insulin-like growth factor binding protein-3 degrading activity was observed in rat-serum. In conclusion, there is an insulin-like growth factor binding protein-3 proteolytic activity in wound fluid, and it is hypothesized that this activity results in a localized increase in insulin-like growth factor-I bioactivity.     

Epidemiology of acquired immunodeficiency syndrome and human immunodeficiency virus infection in adolescents

The epidemiology of acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus infection (HIV) in adolescents is important for purposes of prevention and car, since sexual and drug behavior is formed during this period. For 1990 the Centers for Disease Control reports .4% of AIDS cases are among adolescents 13-19 years old; this figure has steadily risen since 1982. 53% of the reported AIDS cases were from New York, Florida, California, Texas, Puerto Rico, and New Jersey, and has remained stable since 1984. 72% were from metropolitan areas of 1 million population, with a small decreasing trend between 1986-88. 75% of reported cases occurred between 17-19 years, and usually among males (80%) and ethnic minorities (36% African Americans and 18% Hispanics). The sex ratio dropped from 4:1 to 3:1 in 1988. Modes of transmission; indicator diseases and mortality; HIV seroprevalence data; risk of HIV transmission in adolescents; knowledge, attitudes, beliefs, and behavior; research needs; and prevention are discussed. From the studies available, it is reported that adolescents are aware that sexual intercourse and sharing IV drug needles are the main modes of HIV transmission. HIV transmission is more likely to be associated with homosexual contact. Misconceptions are that one could tell if a person were infected with HIV. Knowledge does not always translate to appropriate behavior. Perceived risk does decrease risky behavior, i.e., through abstinence or condom use. More information was desired. Research needs were identified as lagging behind present knowledge of children and adults, and necessary in clinical, epidemiologic, behavioral, and prevention aspects. The natural history of infection is limited to studies of hemophilia, where infected adolescents may have a lower rate of progression to AIDS or a longer incubation period or higher tolerance to severe immunodeficiency. Questions arise concerning the unique factors, such as hormonal changes, that influence the clinical course of the infection. Health care models need to be assessed. Identification of subpopulations that are at the highest risk is needed, i.e., the influence of the crack cocaine epidemic on HIV transmission. Prevention is seen in terms of new creative approaches, comprehensive school and nonschool health education, and behavioral techniques to avoid risky behavior throughout the health community.