Transferring AAC intervention to the home

Purpose: To evaluate the acquisition of AAC skills during an initial clinical trial and assess subsequent transfer of the training to the home setting. Method: A 12-year-old male with autism was first seen in a clinical setting to establish the use of a voice-output communication device. After learning to use the device to request access to preferred objects in the clinical trial, the intervention was transferred to the home. Follow-up with the parent was conducted via e-mail and telephone. Videotapes were made of initial home-based sessions to enable evaluation of the participant's progress. Results: The programme was successful in teaching the participant to use a portable AAC device to make requests during the clinical trial and then in two home-based activities. Conclusion: An initial clinical trial with follow-up support for parents may be an efficient method for beginning AAC intervention and transferring the training procedures to the home setting.     

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.     

Lead poisoning and the deceptive recovery of the critically endangered California condor

Endangered species recovery programs seek to restore populations to self-sustaining levels. Nonetheless, many recovering species require continuing management to compensate for persistent threats in their environment. Judging true recovery in the face of this management is often difficult, impeding thorough analysis of the success of conservation programs. We illustrate these challenges with a multidisciplinary study of one of the world's rarest birds-the California condor (Gymnogyps californianus). California condors were brought to the brink of extinction, in part, because of lead poisoning, and lead poisoning remains a significant threat today. We evaluated individual lead-related health effects, the efficacy of current efforts to prevent lead-caused deaths, and the consequences of any reduction in currently intensive management actions. Our results show that condors in California remain chronically exposed to harmful levels of lead; 30% of the annual blood samples collected from condors indicate lead exposure (blood lead ≥ 200 ng/mL) that causes significant subclinical health effects, measured as >60% inhibition of the heme biosynthetic enzyme δ-aminolevulinic acid dehydratase. Furthermore, each year, ～20% of free-flying birds have blood lead levels (≥450 ng/mL) that indicate the need for clinical intervention to avert morbidity and mortality. Lead isotopic analysis shows that lead-based ammunition is the principle source of lead poisoning in condors. Finally, population models based on condor demographic data show that the condor's apparent recovery is solely because of intensive ongoing management, with the only hope of achieving true recovery dependent on the elimination or substantial reduction of lead poisoning rates.     

Drift-barrier hypothesis and mutation-rate evolution

Mutation dictates the tempo and mode of evolution, and like all traits, the mutation rate is subject to evolutionary modification. Here, we report refined estimates of the mutation rate for a prokaryote with an exceptionally small genome and for a unicellular eukaryote with a large genome. Combined with prior results, these estimates provide the basis for a potentially unifying explanation for the wide range in mutation rates that exists among organisms. Natural selection appears to reduce the mutation rate of a species to a level that scales negatively with both the effective population size (N_e), which imposes a drift barrier to the evolution of molecular refinements, and the genomic content of coding DNA, which is proportional to the target size for deleterious mutations. As a consequence of an expansion in genome size, some microbial eukaryotes with large N_e appear to have evolved mutation rates that are lower than those known to occur in prokaryotes, but multicellular eukaryotes have experienced elevations in the genome-wide deleterious mutation rate because of substantial reductions in N_e.     

Stimulation of eosinophil production in vitro by eosinophilopoietin and spleen-cell-derived eosinophil growth-stimulating factor

Eosinophilopoietin (EPP) was previously characterized by the ability to stimulate eosinophil production in vivo, but these studies could not ascertain whether EPP had a direct effect on the bone marrow or acted indirectly by causing release of eosinophilopoietic activity by other tissues. The present studies demonstrate that EPP stimulates eosinophil growth in liquid culture of mouse bone marrow in vitro. The timing of stimulation by EPP in vivo and in vitro were parallel, with maximal eosinophil growth after 48 hr. Moreover, EPP appears similar to, and possible identical with, the eosinophil growth-stimulating substance (EO-GSF) released by antigenic stimulation of immune nonadherent spleen cells. Both EPP and EO-GSF are of low molecular weight, both produce stimulation of eosinophil growth with identical kinetics, and both produced similar dose-response curves in the liquid culture system.     

Role of thromboxane and prostacyclin release on photodynamic therapy-induced tumor destruction

Thromboxane and prostacyclin levels in serum were measured following photodynamic therapy (PDT) to assess the role of these vasoactive agents on vascular damage and tumor destruction. Sprague Dawley rats were given injections i.v. of Photofrin II doses ranging from 0 to 25 mg/kg. Twenty-four h later, the right hindlimbs of animals bearing chondrosarcoma tumor or controls were exposed to 0-135 J/cm2 630 nm light. Serum concentrations of thromboxane and prostacyclin were determined by radioimmunoassay. A dose-response relationship was established between the amount of photosensitizer administered and the light dose delivered with the release of thromboxane immediately following PDT. Treatment of tumor induced higher levels of thromboxane than did the treatment of tumor-free tissue, suggesting that tumor is more sensitive to PDT-induced damage. The porphyrin and light doses found to induce the release of thromboxane into serum were the same as those required to evoke vascular stasis and tumor destruction. Prostacyclin release was not altered by PDT. The administration of indomethacin (10 mg/kg, i.p.) 3 h before light treatment was found to suppress the intravascular release of thromboxane at the highest porphyrin and light doses studied. Indomethacin treatment also inhibited PDT-induced vascular stasis and tumor destruction, suggesting that the release of thromboxane is linked to these events. Since prostacyclin levels in serum were unchanged following PDT treatment of tumor and controls, thromboxane release appears to be a specific response to PDT and may mediate the vascular stasis observed following PDT.     

The carcinogenic potential of twelve refined mineral oils following long-term topical application.

Twelve mineral oils, originating from naphthenic and paraffinic stocks and variously refined, were evaluated for their potential to induce cutaneous neoplasia in female CF1 mice. The oils were applied to the shorn dorsal skin for up to 78 weeks, using several different treatment regimes. The sole acid/earth refined naphthenic spindle oil was a moderately potent cutaneous carcinogen. By comparison, the 11 oils, processed by other refining routes, were less carcinogenic or non-carcinogenic to murine skin. Two of the 11 oils were weak cutaneous carcinogens viz, a naphthenic spindle oil refined only by mild hydrotreatment and a paraffinic spindle oil refined by mild solvent extraction and ''Ferrofining''. All 9 remaining oils had been solvent-extracted as part of the secondary refining process; none induced malignant tumours, although solitary benign tumours of the treated site were recorded after exposure to 3 oils. The cutaneous carcinogenic potential of the test oils did not correlate well with their potential to induce epidermal hyperplasia at the treated site. Consequently, hyperplasia caused after short term exposure is of little value for distinguishing between carcinogenic and non-carcinogenic oils.     

Bioavailability of Phenytoin Acid and Phenytoin Sodium with Enteral Feedings

Study Objective . To compare the absolute bioavailability of phenytoin (PHT) sodium solution and PHT acid suspension in healthy volunteers receiving continuously infused enteral feedings. Design . Randomized, open-label, single-dose, three-period crossover study. Setting . University clinical research center. Subjects . Ten healthy volunteers age 23–43 years. Interventions . The three phases of the study were separated by at least 7 days. During phase A, subjects received PHT sodium 435 mg intravenously over 30 minutes. During phases B and C, subjects had a nasogastric feeding tube placed through which PHT acid suspension 400 mg and PHT sodium solution 435 mg were administered, respectively. For phases B and C, continuous enteral feedings were given by feeding tube for 14 hours before and after the PHT dose. Blood samples were collected over 72 hours after each PHT dose, and the serum was analyzed for PHT. Measurements and Main Results . The rate and extent of PHT absorption and PHT pharmacokinetics were determined using an empirical quadratic function of time method. Bioavailability, rate of absorption, maximum concentration (C_max), and time to maximum concentration (T_max) were compared for the two enteral doses by paired Student's t test. There were no significant differences in bioavailability for PHT acid suspension and PHT sodium solution (0.88 ± 0.15 vs 0.91 ± 0.7, p=0.57, 90% CI −0.14–0.071). The C_max was greater (7.4 ± 0.9 mg/L vs 5.5 ± 1.7 mg/L, p=0.019) and T_max was less (2.5 ± 3.8 vs. 14.8 ± 11.2 hrs, p=0.004) for the sodium solution. The time to 50% fractional absorption (0.33 ± 0.08 vs 3.2 ± 2.4 hrs, p=0.004) and 90% fractional absorption (7.9 ± 6.2 vs 22.3 ± 17.2 hrs, p=0.021) was also significantly shorter for the sodium solution. Conclusion . The absolute bioavailability of the two dosage forms of PHT administered with concomitant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solution being more rapidly absorbed.     

Body Surface Mapping and Nontraditional ECG Leads in Patients with Wolff-Parkinson-White Syndrome

A method of ECG mapping from 90 points on the chest surface is described in 41 male and 17 female patients, aged 6 to 59 years. All also underwent invasive electrophysiological investigation and intraoperative epicardial mapping. Fifty-two patients had one, three patients two, and one patient had three anomalous accessory pathways. Two patients had nodoventricular tracts (Mahaim fibers). We distinguished seven zones along the atrioventricular groove (AVG) to compare the data derived from epicardial, endocardial, and body surface mapping. A microcomputer was used for the analysis of all ECGs to construct and analyze the isopotential maps. The criterion for localization of the anomalous accessory pathways was determined after analysis of the data from all 58 patients. The localization criterion was the appearance of a minimal deflection (-0.09 +/- 0.03 mV) on the surface isopotential maps within the first 0.28 msec of the QRS complex. This criterion for localization of anomalous accessory pathways from the chest surface was proposed on the basis of comparison of data from selective coronary angiography, the ventriculogram, and the chest X ray i.e., radiographic-topographic-anatomical data. In 20 patients, 10-20 nontraditional ECG leads were recorded from the chest to reflect the atrioventricular groove. The number of nontraditional ECG leads depended on patient age, weight, and height. Localization of the accessory pathway in one of the seven zones was established by the earliest delta wave and its maximum deviation. It was possible to localize the anomalous accessory pathway and to suspect multiple pathways in 95% of cases using nontraditional ECG leads and the listed criteria.(ABSTRACT TRUNCATED AT 250 WORDS)