Utilization of palliative care consultations in pediatric oncology phase I clinical trials

Pediatric phase I clinical oncology trials represent a unique cohort of patients who have not responded to standard therapies and remain highly vulnerable to treatment toxicity and/or disease burden. Incorporating a palliative care consultation into the care plan for those with relapsed/refractory cancer where chance of cure is limited is generally recommended. A retrospective chart review of pediatric phase I trials revealed that palliative care was consulted in <20% of patients, most often for symptom management. Efforts to increase the use of palliative services in this population may enhance quality of life for children and families enrolled in phase I studies.     

Characterization of virus-like particles produced by a recombinant baculovirus containing the gag gene of the bovine immunodeficiency-like virus.

The entire gag gene of the bovine immunodeficiency-like virus (BIV) was inserted behind the strong polyhedron promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). The resultant recombinant baculovirus (AcNPV-BIVgag) was used to infect insect cells in order to overexpress and characterize BIV gag gene products. The infection resulted in the high-level expression of a protein similar in size to the predicted BIV gag precursor (Pr53gag). BIV Pr53gag was detected in AcNPV-BIVgag-infected insect cells and in culture supernatants. Electron microscopy of these cells revealed an abundance of virus-like particles (VLPs) in the cytoplasm, budding from the cell membrane, and free in the culture medium. The size and morphology of the VLPs were similar to those of the immature forms of BIV observed in infected mammalian cells. The VLPs sedimented at a density of 1.16 g of sucrose per milliliter in linear gradients and were shown to contain the majority of the supernatant Pr53gag. Antigenic determinants on Pr53gag from VLPs were recognized by BIV and HIV-1 antiserum, and serum from rats immunized with VLPs reacted with recombinant and viral BIV Pr53gag and processed products. The protease (PR) activity in BIV virions was capable of processing recombinant Pr53gag; this activity was blocked by pepstatin A, a potent aspartyl PR inhibitor. Baculovirus-expressed BIV Pr53gag appears to be an excellent source of gag precursor; it may prove useful for structural studies and enable the development of assays to detect retroviral PR inhibitors. The data further suggest that unprocessed BIV Pr53gag plays a major role in the assembly of BIV particles. The expression of other BIV structural genes in insect cells may prove instructive in the study of molecular events involved in the assembly and processing of these BIV proteins.     

Effects of fixed-ratio schedule values on concurrent mands in children with autism

Interventions with children with autism often involve more than one concurrent schedule or reinforcement. Manipulation of one schedule of reinforcement may affect responding on a second. We demonstrated the effect of manipulating the schedule of reinforcement for a single high-rate mand on alternative concurrently available mands with two children with autism. Teachers conducted sessions in the participant's usual teaching environment. When the schedule value for all mands was FR1, a single mand occurred at a high rate while all other mands occurred at low rates for both participants and response variability was low. When the schedule of reinforcement for the high-rate mand increased to FR10 for one participant and to FR25 for the second participant, and all other mands remained on FR1 schedules, the high-rate mand decreased while the combined rate of all other mands increased. There was also some evidence of increased response variability. We discuss the affects of schedule values during concurrent schedules and implications for increasing variability in manding.     

Comparison of frontal plane trunk kinematics and hip and knee moments during anticipated and unanticipated walking and side step cutting tasks

BACKGROUND: Frontal plane trunk and lower extremity adjustments during unanticipated tasks are hypothesized to influence hip and knee neuromuscular control, and therefore, contribute to anterior cruciate ligament (ACL) injury risk. The aims of this study were to examine frontal plane trunk/hip kinematics and hip and knee moments (measures of neuromuscular control) during unanticipated straight and side step cut tasks. METHODS: Kinematic and kinetic variables were collected while subjects performed two anticipated tasks, including walking straight (ST) and side step cutting (SS), and two unanticipated tasks (STU and SSU). Foot placement, thorax-pelvis-hip kinematic variables and hip and knee moments were calculated over the first 30% of stance. FINDINGS: Hip abduction angles and knee moments were significantly affected by task and anticipation. Hip abduction angles decreased, by 4.0-7.6 degrees , when comparing the SSU task to the ST, STU and SS tasks. The hip abduction angles were associated with foot placement and lateral trunk orientation. INTERPRETATION: Hip abduction angles and foot placement, not lateral trunk flexion influence trunk orientation. Anticipation influences hip and knee neuromuscular control and therefore may guide the development of ACL prevention strategies.     

Perivascular noradrenergic and peptide-containing nerves show different patterns of changes during development and ageing in the guinea-pig

The development of noradrenergic and peptide-containing perivascular nerves in common carotid, mesenteric, renal and femoral arteries of the guinea-pig was studied using the glyoxylic acid fluorescence and indirect immunofluorescence techniques on whole-mount stretch preparations at 6 stages between 6 weeks in utero and two years after birth. The noradrenergic plexus was more dense than the peptide-containing nerve plexuses in all the blood vessels, and, in general, calcitonin gene-related peptide-containing nerves were more numerous than substance P-containing nerves which in turn were more numerous than vasoactive intestinal polypeptide-containing nerves. In mesenteric and carotid arteries, noradrenergic nerve density reached a peak at about 4 weeks after birth that was maintained to old age, whereas the peptide-containing vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) nerve plexuses reached a peak at birth and declined thereafter to about half maximum density in old age. In contrast, in the renal and femoral arteries, peptide-containing nerves reached a maximum density at 4 weeks after birth, while noradrenergic nerve density reached a peak around birth; both noradrenergic and peptide-containing nerve plexuses declined in density in old age. Of the 4 vessels studied, the mesenteric artery showed the greatest density of innervation for both noradrenergic and peptide-containing nerves at all stages of development, while the femoral artery was the least innervated. The possibility that some perivascular peptide-containing nerves play a trophic role during development is discussed.     

Intramural neurons of the guinea-pig urinary bladder: histochemical localization of putative neurotransmitters in cultures and newborn animals

Histochemical methods have been used to study the distribution of putative neurotransmitters in the urinary bladder of newborn guinea-pigs and in cultures of intramural ganglia. Following the nicotinamide adenine dinucleotide (NADH)-diaphorase reaction which specifically labels nerve cell bodies, up to 66 ganglia were observed in stretch preparations of the newborn urinary bladder. Each ganglion contained 2-50 nerve cell bodies. Vasoactive intestinal polypeptide was localized in a few nerve cell bodies of intramural ganglia both in in situ and culture preparations. In the in situ preparations it was widely distributed in nerve fibres to the muscle, being most dense at the base of the bladder, and in some mucosal epithelial cells. Somatostatin was contained in numerous neuronal cell bodies in the detrusor muscle both in situ and in culture. Extensively distributed varicose fibres were found in culture and in the muscle, submucous and mucosal layers in situ. Substance P immunofluorescence was demonstrated in a few neuronal cell bodies in ganglia both in situ and in vitro, particularly in those of the mucosa at the base of the bladder. In the in situ preparations varicose nerve fibres containing substance P were seen in the muscle coats with greatest density in the bladder base. Met-enkephalin-immunoreactive nerve cell bodies were not seen either in situ or in culture. Nerve fibres in in situ preparations were found largely enveloping neuronal cell bodies within the ganglia. Neither serotonin-immunoreactive nor catecholamine-containing neuronal cell bodies were seen in the in situ bladder preparation. However, some nerve cell bodies in culture showed positive staining, possibly as a result of selective uptake of serotonin and catecholamine known to be contained in foetal calf serum in the culture medium or possibly as the result of increased synthetic activity in certain neurones in the culture situation. In whole-mount stretch preparations, no serotonin-immunoreactive nerve fibres were seen, but catecholamine-containing small intensely fluorescent cells and nerve fibres were observed. Acetylcholinesterase-positive nerve cell bodies and nerve fibres were observed both in in situ and culture preparations of the bladder. Quinacrine-positive nerve cell bodies (as an indicator of purinergic neurones) were found in numerous intramural neurones examined. in situ; however, under the culture conditions used, non-selective staining of all cell types occurred.     

Prolonged antinociception following carbon dioxide anesthesia in the laboratory rat

In the laboratory rat, inhalation (30 s) of high (> 70%) CO₂ concentrations resulted in short-term (1–3 min) anesthesia, followed by a prolonged (up to 60 mn) mild antinociception. Exposure to 100% CO₂ resulted in significant thermal (hot-plate, 52°, and tail-flick) and mechanical (tail-pinch, 886 g force) antinociception. Control animals, placed in the same chamber filled with air, showed no such effects. Rats exposed to 70% CO₂ exhibited effects on the hot plate comparable to those seen after inhalation of 100% CO₂, indicating that the response is not due to CO₂-induced hypoxia. Additionally, recovery from halothane-induced anesthesia of comparable duration did not result in antinociception, confirming that anesthesia alone is not sufficient to produce the effect. Pretreatment with the opiate antagonist naltrexone (0.1–10 mg/kg i.p.) did not diminish the CO₂-induced antinociception, suggesting that endogenous opioids are not obligatory in the mechanism of this response. Furthermore, hypophysectomy abolished hot-plate antinociception in animals exposed to 100% CO₂ while sham-treated controls exhibited a pattern of hot-plate responses similar to that reported above. Taken together, these findings show that: (1) recovery from CO₂-induced anesthesia results in a prolonged mild antinociception, detectable with thermal and mechanical nociceptive tests; and (2) this response may represent a novel form of environmentally induced antinociception, mediated by a non-opiate hormonal substance.     

Short–Term Effects of Nicotine on Bone and Calciotropic Hormones in Adult Female Rats

Abstract: This study assessed the effects of two months nicotine treatment on bone formation and resorption end–points in adult, female rats. In addition, the concentrations of calciotropic hormones which included parathyroid hormone, calcitonin, 25–hydroxyvitamin D and 1,25–dihydroxyvitamin D in rats (7 months old) were determined. All animals received either saline (n = 7/group). nicotine (3.0 mg/kg/day) (n = 7/group) or nicotine (4.5 mg/kg/day) (n = 7/group) via subcutaneous implantation of osmotic minipumps containing either saline or nicotine for a period of two months. Serum, right tibia, left femur and lumbar vertebra (3–5) were collected for determination of hormonal concentrations as well as various parameters, including histomorphometry, bone mineral density, bone mineral content and vertebral strength. Although nicotine–treated rats showed a lower level of 25–hydroxyvitamin D [54.4 × 3.1 ng/ml for the 3.0 mg/kg/day and 55.8 × 2.8 for the 4.5 mg/kg/day group] (mean × S.E.M.) as compared to controls (74.8 × 2.8 ng/ml) (P < 0.01, Newman–Keuls test), no significant difference could be detected for the levels of the remaining hormones. Similarly, no statistical differences were detected on histomorphometric end–points, bone mineral density, bone mineral content and vertebral strength of rats. We conclude that, in spite of lowering serum 25–hydroxyvitamin D by about 30%, nicotine administration of two months duration does not alter bone mass, strength or formation and resorption end–points.     

The effect of caffeinated, non-caffeinated, caloric and non-caloric beverages on hydration

OBJECTIVE: To examine the effect of various combinations of beverages on hydration status in healthy free-living adult males. METHODS: In a counterbalanced, crossover manner, 18 healthy adult males ages 24 to 39, on four separate occasions, consumed water or water plus varying combinations of beverages. Clinical guidelines were used to determine the fluid allowance for each subject. The beverages were carbonated, caffeinated caloric and non-caloric colas and coffee. Ten of the 18 subjects consumed water and carbonated, non-caffeinated, citrus soft drink during a fifth trial. Body weight, urine and blood assays were measured before and after each treatment. RESULTS: Slight body weight loss was observed on all treatments, with an average of 0.30% for all treatments. No differences (p>0.05) among treatments were found for body weight changes or any of the biochemical assays. Biochemical assays conducted on first voids and 24-hour urines included electrolytes, creatine, osmolality and specific gravity. Blood samples were analyzed for hemoglobin, hematocrit. electrolytes, osmolality, urea nitrogen, creatinine and protein. CONCLUSIONS: This preliminary study found no significant differences in the effect of various combinations of beverages on hydration status of healthy adult males. Advising people to disregard caffeinated beverages as part of the daily fluid intake is not substantiated by the results of this study. The across-treatment weight loss observed, when combined with data on fluid-disease relationships, suggests that optimal fluid intake may be higher than common recommendations. Further research is needed to confirm these results and to explore optimal fluid intake for healthy individuals.     

Data-reduction methods for immunoradiometric assays of thyrotropin compared

In an attempt to optimize curve fitting for immunoradiometric assays, we investigated eight data-reduction methods with two commercially available assays of thyrotropin. In four of these methods linear data-reduction models are used: logit-log programs of Iso-Data, Micromedic, and Hewlitt-Packard, and probit-log of Hewlitt-Packard. The other four were nonlinear data-reduction models: Iso-Data's "French curve" (modified spline), four-parameter logistic function, and point-to-point methods, as well as a nonlinear least squares method. In using the eight data-reduction methods on data from analyses of 78 patients' samples, we found clinically relevant differences between models. In fact, differences found by changing data-reduction models were greater than the difference between the two commercial kits.