Manual and computer-aided space analysis: a comparative study

Separate injections of Haemophilus influenzae type b capsular polysaccharide-tetanus conjugate (PRP-T) vaccine and diphtheria-tetanus-pertussis (DTP) reconstitution of freeze-dried PRP-T vaccine with liquid DTP vaccine have been shown to be safe and immunogenic in infants. The present study was conducted to test the safety and immunogenicity of the liquid combination vaccine administered to young infants in the dual-chamber syringe. The study was a monocenter, open clinical trial of 3 month-old infants receiving PRP-T and DTP vaccines in the dual-chamber syringe reconstituted prior to injection. Healthy infants were immunized according to a 3, 4 and 5 months-of-age schedule. The vaccine was administered in a dual-chamber syringe, ready to use with two chambers. The proximal chamber contained freeze-dried PRP-T and the distal chamber contained liquid combination-vaccine DTP. The freeze-dried PRP-T vaccine was reconstituted with the liquid DTP vaccine in the same unidose dual-chamber syringe (0.5 mL) and was injected intramuscularly into the deltoid region. Blood sampling was performed prior to vaccination at 3 months of age and after the third vaccination at 6 months. The primary end-point was the serological response to PRP-T vaccine as expressed by the percentage of infants with an antibody titer greater than or equal to 1 microgram/mL. The reactogenicity was expressed as the percentage of reported local and systemic reactions. A total of 108 infants were included in the study and received the dual-chamber syringe vaccine. After the third injection, all the infants had a PRP antibody titer greater than or equal to 0.15 microgram/mL and 94.4% of infants had a PRP antibody titer greater than or equal to 1 microgram/mL; the pertussis agglutinin titers were over the threshold 40 and 80 in all infants and 98.1% were over the threshold 320. After the third injection, all the infants had diphtheria antibody titers greater than 0.1 IU/mL and 83.3% had titers greater than 1 IU/mL; all the infants had tetanus antibody titers greater than 0.1 IU/mL and 97.2% had results over 1 IU/mL. Thirty-seven infants (34.6%) had local reactions and 64.5% had systemic reactions. The dual-chamber syringe may reduce the cost of vaccine delivery, as well as the workload, and increase the vaccine acceptability and coverage rate of vaccines.     

T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis

To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43 microfilaremics, 12 symptomatic amicrofilaremics, and 52 elephantiasis patients. Lymphocyte proliferation was higher in elephantiasis patients and asymptomatic amicrofilaremics than in microfilaremics (P < .004). A proportion of asymptomatic amicrofilaremics (32%), elephantiasis patients (37%), and symptomatic amicrofilaremics (58%) showed antigen-specific lymphocyte unresponsiveness, and lymphocyte proliferation to filarial antigens correlated negatively with specific IgG4 levels (rho = -0.315, P < .001). As elevated specific IgG4 is an indicator of active infection, it is argued that active infection may result in lymphocyte hyporesponsiveness irrespective of clinical category. Of those with elevated specific IgE levels and high T cell proliferative responses, 70% had elephantiasis, suggesting these factors have a role in pathology. However, the existence of a proportion of elephantiasis patients with low anti-filarial IgE and T cell unresponsiveness to filarial antigens suggests that elephantiasis can be caused by distinct processes.     

Imitation and pantomime in high-functioning adolescents with autism spectrum disorders

A study was designed to test 2 alternative hypotheses--a symbolic hypothesis and an executive function hypotheses--for the imitation and pantomime deficits found in previous studies of autism. The subjects were 17 adolescent high-functioning subjects with autism spectrum disorders and 15 clinical comparison subjects who were matched on chronological age and verbal IQ. Meaning and sequence were manipulated in facial and manual imitation tasks. Sequence was manipulated in the pantomime and control tasks. Recognition memory and motor control tasks were matched to the experimental tasks. The results provided no support for the symbolic deficit hypothesis; meaning aided rather than hindered the performance of the group with autism. Partial support for the executive deficit hypothesis was found. There were no group differences on motor control tasks, and few on the memory control tasks, arguing against deficits in motor initiation, basic motor coordination, or visual recognition memory.     

Adverse environmental conditions in the respiratory and medical ICU settings

Sleep deprivation and fragmentation occurring in the hospital setting may have a negative impact on the respiratory system by decreasing respiratory muscle function and ventilatory response to CO2. Sleep deprivation in a patient with respiratory failure may, therefore, impair recovery and weaning from mechanical ventilation. We postulate that light, sound, and interruption levels in a weaning unit are major factors resulting in sleep disorders and possibly circadian rhythm disruption. As an initial test of this hypothesis, we sampled interruption levels and continuously monitored light and sound levels for a minimum of seven consecutive days in a medical ICU, a multiple bed respiratory care unit (RCU) room, a single-bed RCU room, and a private room. Light levels in all areas maintained a day-night rhythm, with peak levels dependent on window orientation and shading. Peak sound levels were extremely high in all areas representing values significantly higher than those recommended by the Environmental Protection Agency as acceptable for a hospital environment. The number of sound peaks greater than 80 decibels, which may result in sleep arousals, was especially high in the intensive and respiratory care areas, but did show a day-night rhythm in all settings. Patient interruptions tended to be erratic, leaving little time for condensed sleep. We conclude that the potential for environmentally induced sleep disruption is high in all areas, but especially high in the intensive and respiratory care areas where the negative consequences may be the most severe.     

Neural network payload estimation for adaptive robot control

A concept is proposed for utilizing artificial neural networks to enhance the high-speed tracking accuracy of robotic manipulators. Tracking accuracy is a function of the controller's ability to compensate for disturbances produced by dynamical interactions between the links. A model-based control algorithm uses a nominal model of those dynamical interactions to reduce the disturbances. The problem is how to provide accurate dynamics information to the controller in the presence of payload uncertainty and modeling error. Neural network payload estimation uses a series of artificial neural networks to recognize the payload variation associated with a degradation in tracking performance. The network outputs are combined with a knowledge of nominal dynamics to produce a computationally efficient direct form of adaptive control. The concept is validated through experimentation and analysis on the first three links of a PUMA-560 manipulator. A multilayer perceptron architecture with two hidden layers is used. Integration of the principles of neural network pattern recognition and model-based control produces a tracking algorithm with enhanced robustness to incomplete dynamic information. Tracking efficacy and applicability to robust control algorithms are discussed.     

The effects of chronic high dose androgen or estrogen treatment on the human prostate [corrected

Prostate development and disease are androgen dependent. However, the nature of hormonal effects on the prostate of healthy young men is not clear. We, therefore, measured prostate size in males chronically exposed to high doses of androgens (AS; habitual anabolic steroid abusers; n = 15) or estrogens (E; male to female transsexuals; n = 11) and compared the results with those in age-matched healthy eugonadal men without known prostate disorders. Prostate size was measured by planimetric ultrasound as cross-sectional areas and maximal dimensions in three orthogonal dimensions with a 7.5-megahertz B-mode sector scanner biplane in a transrectal transducer at 2.5 mm steps from the base to the apex of prostate. Total prostate volume (TPV) was reconstructed from planimetric sections, central prostate volume (CPV) was calculated by the ellipsoidal formula from the appropriate three maximum dimensions, and peripheral prostate volume was determined by the difference between TPV and CPV. Compared with age-matched controls, TPV was normal (-2%) in AS (P = 0.752) and reduced by 31% in E (P = 0.002), whereas CPV was increased by 20% in AS (P = 0.002) and reduced by 46% in E (P = 0.002), and the ratio of CPV/peripheral prostate volume was increased by 77% in AS (P < 0.001) and decreased by 33% in E (P = 0.047). Blood sex hormone-binding globulin was elevated by nearly 500% in E (P < 0.001), but was reduced by 47% in AS (P = 0.003). Prostate-specific antigen was normal (-6%) in AS (P = 0.799) and decreased by 86% in E (P = 0.002). Prostatic acid phosphatase was increased by 26% in AS (P = 0.007), but was unchanged (-28%) in E (P = 0.106). Total and free testosterone levels were reduced to castrate levels in E, whereas LH, FSH, and total testosterone levels were significantly reduced in AS. We conclude that in the human prostate of young men, CPV is more hormonally sensitive than TPV, and during high dose treatment, CPV is preferentially increased by chronic androgen treatment and decreased by chronic estrogen treatment. The reduction of TPV by estrogens was less than expected if solely attributable to inhibition of endogenous gonadotropin and testosterone secretion, suggesting that estrogens also have a positive effect on the normal human prostate. The reversibility and long term significance of androgen-induced stimulation of CPV and, in particular, its relationship to the onset and severity of benign prostatic hyperplasia remain to be clarified.     

Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.