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Biomedical subjects

E L Hill

Publications and source records attributed to E L Hill.

At least 19 recordsLinked to original sources

Action-monitoring and intention reporting in children with autism.

The " mindblindness" theory of core cognitive impairment in autism and at least one of the executive theories of the core cognitive deficit both predict that children with autism should find it difficult to report what their intention was when it diverged from an outcome. The former predicts this because it takes intention reporting to require a " theory of mind " and the latter predicts it because the theory posits an impairment in the monitoring of goal-directed actions. The latter also predicts impairments in the ability to monitor basic actions. Our three studies failed to support either of these views. Experiment 1 demonstrated intact abilities in the monitoring of basic actions (detecting which stimulus of a number of stimuli one is controlling). Experiment 2 demonstrated intact abilities in reporting an intention, both for self and for another agent, when the outcome was unintended but desired. In Experiment 3, using the novel "transparent intentions task", we found (with a minor qualification) intact ability in reporting on nonballistic intended actions when the result that the action achieved was unexpected. The implications of these results for views of the relation between theory of mind and executive difficulties in autism are discussed.

Autistic Disorder↗

A reaching test reveals weak hand preference in specific language impairment and developmental co-ordination disorder.

A reaching test for quantifying hand preference (QHP task) was given to 7- to 11- year-old children with specific language impairment (SLI) or developmental coordination disorder (DCD). The performance of these clinical children was compared to both an age-matched and younger control group. The four groups did not differ in terms of preferred writing hand or preference on a handedness questionnaire. The QHP measure discriminated the clinical and younger control groups from the age-matched controls, but not from each other. Right-handed children with SLI, DCD, and the younger controls reached predominantly with the right hand to spatial positions located to the right of their body's midline and with the left hand to positions situated to its left. Right-handers in the age-matched control group showed a significantly greater tendency to use their right hand to reach to all spatial positions. The increased tendency of the children with SLI to use the non-preferred hand was particularly striking because it was seen both in those with and without recognised motor difficulties. The QHP task appears to be a sensitive, but non-specific, indicator of developmental disorders.

Journal Article↗

Chronic vulvar ulceration in an immunocompetent woman due to acyclovir-resistant, thymidine kinase-deficient herpes simplex virus.

A 34-year-old healthy woman presented with a 15-month history of persistent, nonhealing vulvar ulcerations due to herpes simplex virus (HSV) type 2. Extensive dermatologic workup and serial skin biopsies failed to reveal an underlying vulvar dermatosis or autoimmune bullous disorder. Virologic studies revealed resistance to acyclovir in vitro due to deficiency in thymidine kinase activity. Serum antibody to human immunodeficiency virus was negative on two occasions, separated by 1 year. Immunologic evaluation showed normal HSV-specific proliferative and CD8 cytotoxic T lymphocyte responses as well as normal NK cell function. Vulvar lesions failed to heal in association with trials of topical trifluorothymidine and oral valacyclovir but resolved completely with the application of 1% foscarnet cream. No recurrence of HSV has been observed in 24 months of follow-up to date.

Acyclovir↗

A dyspraxic deficit in specific language impairment and developmental coordination disorder? Evidence from hand and arm movements.

The extent to which children with either specific language impairment (SLI) or developmental coordination disorder (DCD) could be considered dyspraxic was examined using three tasks involving either familiar, or unfamiliar actions. SLI is diagnosed in children who fail to develop language in the normal fashion for no apparent reason, while the DCD diagnosis is applied to a child who experiences problems with movement in the absence of other difficulties. Seventy-two children aged between 5 and 13 years participated, falling into one of four groups: (1) children with specific language impairment (SLI), (2) children with developmental coordination disorder (DCD), (3) age-matched control children, and (4) younger control children. The performance of the clinical groups resembled that of younger normally developing children. Children with SLI, DCD, and the younger controls showed significant difficulty on the task requiring the production of familiar, but not unfamiliar postures. The deficit observed in the SLI group is particularly striking because it was seen both in those with and those without recognized motor difficulties.

Adolescent↗

Variability in post-operative fluid and electrolyte prescription.

A four-week retrospective survey of intravenous fluid and electrolyte prescriptions on post-operative surgical patients revealed wide variability in fluid and electrolyte prescription by medical staff. Median volume of intravenous fluid prescribed was 3000 ml (range 1667-5000). Total sodium prescribed varied from 0 to 770, median 242 mmol/day), with potassium infrequently added (range 0-81, median 0 mmol/day). Patients undergoing emergency surgery were prescribed more sodium than those undergoing routine procedures (p = 0.0403); 0.9% saline was the most common fluid prescribed overall. There was poor correlation between serum electrolyte values and the amounts of electrolytes prescribed. Intravenous fluid prescription should take into account the post-operative stress response which reduces sodium requirements (unless there are other concomitant losses) and increases urinary potassium losses. A suitable post-operative 'maintenance' fluid is 4% dextrose/0.18% saline with 1-2 g potassium chloride, particularly if serum electrolyte levels are not known. Other fluid losses should be replaced with equivalent fluids.

Aged↗

The effect of systemically administered PDGF-BB on the rodent skeleton.

Platelet-derived growth factor (PDGF), an osteoblast mitogen, has been demonstrated to accelerate fracture healing and periodontal bone repair when applied locally in vivo. To explore whether PDGF could stimulate bone formation in intact bone, we administered it systemically to rats rendered acutely estrogen-deficient. Because PDGF may stimulate bone resorption in vitro, PDGF was administered with and without an antiresorptive agent (alendronate). All treatments were given by intravenous injection 3 times a week for 6 weeks. Spinal bone mineral density (BMD) decreased by 5% in the vehicle-treated ovariectomized (OVX) rats by the end of the study as determined by DXA. Treatment with PDGF prevented this bone loss and significantly (p < 0.05) increased the bone density in the spine (9%) and whole skeleton (5.8%). Combined treatment with PDGF and alendronate resulted in a greater increase at the spine (18%) and whole skeleton (12.8%) than either agent alone. Histomorphometric analysis demonstrated that treatment with PDGF increased the osteoblast number and osteoblast perimeter without consistent changes in osteoclast estimates. Biomechanical testing demonstrated that PDGF administration increased the vertebral body compressive strength and femoral shaft torsional stiffness and resulted in a trend for enhanced femoral head shearing strength. Coadministration of alendronate further increased these indices of bone strength. PDGF administration also caused premature closure of the growth plate, decreased body fat, and resulted in extraskeletal collagen deposition. We therefore demonstrate, for the first time, that systemic administration of PDGF can increase bone density and strength throughout the skeleton.

Absorptiometry, Photon↗

Activity, passivity, self-denigration, and self-promotion: toward an interactionist model of interpersonal dependency.

Although dependency in adults is inextricably linked with passivity and submissiveness in the minds of many theoreticians, clinicians, and researchers, evidence has accumulated which suggests that in certain situations, dependency is actually associated with high levels of activity and assertiveness. Three experiments were conducted to test the hypothesis that when a dependent person is concerned primarily with getting along with a peer, he or she will "self-denigrate" (i.e., will utilize strategies that ensure that a peer will be evaluated more positively than he or she is on a laboratory task), but when a dependent person is concerned primarily with pleasing an authority figure, he or she will "self-promote" (i.e., will adopt strategies that increase the likelihood that he or she will be evaluated more positively than a peer on a laboratory task). This hypothesis was supported in all three experiments. Theoretical implications of these findings are discussed, and an interactionist model of interpersonal dependency is briefly described.

Adult↗

Calcitonin gene-related peptide (CGRP) in the developing mouse limb.

The mitogenic effects of neuropeptides and their localization to developing tissues suggest an important role for these peptides during gestation. We examined the expression and action of the neuropeptide calcitonin gene-related peptide (CGRP) in the developing mouse limb bud, an excellent model system for studying musculoskeletal development. CGRP immunoreactivity (CGRP-ir) was detected in the developing limb at day 16.5 of gestation (E 16.5) and was limited to nerve fibers surrounding blood vessels, within the developing muscle or in close proximity to the developing cartilaginous skeleton. Although CGRP-ir was not observed until E 16.5, limb buds were responsive to CGRP as early as E 11.5. Within 5 min of exposure to CGRP (10(-8) to 10(-7) M) a 2--3-fold increase in cyclic AMP (cAMP) levels was observed. This CGRP-induced increase in cAMP was abolished by the addition of human CGRP8-37, a CGRP receptor antagonist. This result suggests that the effect on cAMP was mediated by the interaction of CGRP with CGRP receptors. Our findings indicate that mouse limbs are responsive to CGRP when they are composed of primarily undifferentiated mesenchyme and that CGRP-ir appears at a later stage of development in association with cartilage and muscle differentiation.

Animals↗

Recurrence and resistance patterns of herpes simplex virus following cessation of > or = 6 years of chronic suppression with acyclovir. Acyclovir Study Group.

Questions have arisen regarding the clinical outcome and the possible selection of resistant virus when patients with genital herpes discontinue prolonged chronic acyclovir; 239 immunocompetent patients with a history of frequently recurring genital herpes who stopped successful suppressive therapy after 6 years were studied. Of the patients, 85.8% had at least one recurrence and 75% had at least two recurrences in the subsequent year (median time to first and second recurrence, 68 and 180 days, respectively). Herpes simplex virus isolates recovered from these patients had a median acyclovir sensitivity of 0.79 micrograms/mL and 4 (3.5%) were resistant (> or = 3 micrograms/mL). These values are comparable to those of pretherapy isolates and to reported values of isolates from acyclovir-naive patients. Also, paired pre- and posttherapy isolates from 13 patients showed no trend toward development of resistance. Thus, even after 6 years of acyclovir suppression, most patients continue to have recurrences, but the selection of resistant virus has not been observed.

Acyclovir↗

Retest reliability of scores on objective and projective measures of dependency: relationship to life events and interest interval.

The retest reliabilities of widely used objective and projective measures of dependency were assessed in a mixed-sex sample of undergraduates (54 women and 34 men). Subjects completed Hirschfeld and colleagues' (1977) Interpersonal Dependency Inventory (IDI) and Masling, Rabie, and Blondheim's (1967) Rorschach Oral Dependency (ROD) scale on two occasions separated by 16, 28, or 60 weeks. The IDI and ROD scale showed good retest reliability over 16 weeks in both men and women. However, the ROD scale did not show adequate retest reliability over longer periods in subjects of either sex. IDI scores showed excellent long-term retest reliability in women, but poor long-term retest reliability in men. Subjects' self-reports and impact ratings of life events experienced during the intertest period were unrelated to changes in subjects' IDI and ROD scale scores from Time 1 to Time 2, regardless of the intertest interval used.

Adolescent↗

Changes in bone in a model of spinal cord injury.

Bone calcium, histomorphometry, and mechanical strength were evaluated in a model of spinal cord injury. Cortical bone area and rates of formation and apposition at the tibiofibular junction (TFJ) and midshaft of the humerus were measured at 35-42, 42-77, and 77-94 days after transection of the spinal cord. All comparisons were between the animals with a spinal lesion and control animals. A 0.34% difference in the length of the tibia of the two groups of animals was observed, the dry weight of the tibia was 28.4% less in rats with a lesion, and there was no significant difference in the amount of calcium per milligram of bone. At 35 days after surgery, the cortical area in the midshaft of the humerus was slightly less (11%) in rats with a lesion, but by 94 days there was no difference in cortical or medullary area. The final (day 94) cortical area at the TFJ in rats with a lesion was less than that in the controls. Bone formation at the TFJ was similar in both groups in the period of 35-42 days and was similar at 77-94 days in the animals with a lesion, and rates of formation and apposition were greater in the humerus of rats with a lesion; the rates did not differ significantly between groups at either site. At 94 days, trabecular bone area in the tibial metaphysis was 41% less in rats with a lesion. Mechanical parameters were significantly less in the femora, but not the humeri, of rats with a lesion.

Animals↗

Distribution of CGRP-, VIP-, D beta H-, SP-, and NPY-immunoreactive nerves in the periosteum of the rat.

In light of the possible role peripheral nerves may play in bone metabolism, the morphology of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal peptide (VIP)-, substance P (SP)-, neuropeptide Y (NPY)-, and dopamine-beta-hydroxylase (D beta H)-immunoreactive nerve fibers was examined in whole-mount preparations of periosteum of membranous bones (calvaria, mandible) and long bones (tibia) from the rat. Periosteum from animals treated to remove selectively either the sympathetic or fine-caliber primary afferent nerves was also examined to determine the origin of the nerve fibers. We found a consistent and often dense innervation of the periosteum. The innervation patterns of the calvaria and mandible were similar, with networks of nerves spread across the surface of the bone. Nerves in the tibial periosteum were oriented in the longitudinal axis and were more numerous at the epiphyses than in the mid-shaft region. CGRP-immunoreactive fibers were widely and densely distributed. The presence of populations of CGRP-immunoreactive fibers of differing calibers and perivascular arrangements suggests that such nerves in bone tissues may serve different functions. SP-immunoreactivity was present in a fine network of varicose fibers in the superficial layers of the periosteum. CGRP- and SP-immunoreactive nerve fibers were dramatically reduced in periosteum of capsaicin-treated animals as compared to controls, indicating the sensory origin of these nerves. VIP-immunoreactive nerve fibers were distributed in the periosteum of mandible and calvaria as small networks and individual fine varicose fibers. In tibial periosteum, larger networks of these fibers were visible. VIP-immunoreactive nerve fibers in the periosteum were associated with both vascular and nonvascular elements within the layers of cells closest to the bone, suggesting that VIP may serve more than one function in periosteal tissues. NPY-immunoreactive fibers were largely confined to vascular elements; occasional fibers were observed among the bone-lining cells. D beta H-immunoreactivity was associated only with blood vessels. VIP-, NPY-, and D beta H-immunoreactivities were dramatically reduced in the periosteum of guanethidine-treated animals, indicating the sympathetic origin of these nerves.

Animals↗

Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats.

Bone metabolism may be influenced by the innervation of skeletal tissues. Neuropeptides such as vasoactive intestinal peptide, from sympathetic nerves, and calcitonin gene-related peptide, from sensory nerves, have been implicated as local modulators of bone metabolism. The effect of neonatal sympathectomy and of capsaicin-induced sensory denervation in rats was studied on the following: (i) the radial bone growth and apposition rate in tibiae (normal growth and modeling) and (ii) the percentage of periosteal surface of the mandible occupied by osteoclasts during induced remodeling. Neonate rats were treated with guanethidine, capsaicin, or appropriate vehicle. At seven weeks, maxillary molars were removed to induce remodeling on the buccal surface of the mandible. Animals were killed four days after surgery. Cross-sectional cortical area, medullary area, and periosteal apposition rate were measured by histomorphometry in ground sections of tibiae. The percentage of periosteal surface at the remodeling site occupied by osteoclasts (stained for acid phosphatase) was measured in frozen, undecalcified sections. There was no significant difference in cortical or medullary area or periosteal apposition rate in tibiae between each drug treatment and its control. However, the mandibular bone surface occupied by osteoclasts was increased 45.5% (P less than or equal to 0.005) in animals treated neonatally with guanethidine compared to controls. In contrast, the mandibular surface occupied by osteoclasts was decreased 21.2% (P less than or equal to 0.04) in animals treated neonatally with capsaicin compared to controls. The alteration of bone remodeling (osteoclast surface) by both treatments indicates that sensory and sympathetic nerves play a role in focal metabolism of bone.

Animals↗

In vitro and in vivo characterization of herpes simplex virus clinical isolates recovered from patients infected with human immunodeficiency virus.

A total of 100 herpes simplex viruses isolated from lesions not responding to acyclovir (ACV) therapy were recovered from 51 patients infected with human immunodeficiency virus. In vitro analysis of these isolates included testing their susceptibility to ACV and determining their thymidine kinase (TK) phenotypes. Of the 100 isolates evaluated, 23 were ACV sensitive and 77 were ACV resistant. Seventy-four of these ACV-resistant isolates were of the TK-deficient or low-TK-producer phenotype and three were of the TK-altered phenotype. The TKs isolates that represented each of the different autoradiographic phenotypes were further characterized by enzyme kinetics. The ability of selected isolates to cause disease in vivo was evaluated by using several mouse virulence models. Cutaneous virulence in normal and immunocompromised mice was evaluated, and neurovirulence in normal mice was determined. Latent infections were assayed by the cocultivation of trigeminal ganglia recovered from mice that had survived acute infection. These reactivated viruses were evaluated in vitro and compared with the original infecting isolate. The mechanisms of resistance and pathogenicity of these herpes simplex virus isolates recovered from patients positive for human immunodeficiency virus are similar to those reported for isolates recovered from normal and immunocompromised patients without AIDS.

Animals↗

An improved method for preparing cryostat sections of undecalcified bone for multiple uses.

We developed a technique that permits the use of serial sections (7-20 microns) from a single fixed piece of bone tissue for immunofluorescence, measurement of fluorescent bone labels, enzyme histochemistry, and general staining. This technique combines modifications of previously established methods with perfusion of the polymer polyvinylpyrrollidone (PVP) to improve sectioning, and produces reliable sections with good preservation of both hard and soft tissues. The combination of techniques from several workers, the use of perfusion with a polymer to increase the sectionability of the bone, and the addition of a gelatin adhesive on top of pressure-sensitive adhesives represent a significant improvement over previously described methods. The sections obtained are usable for immunocytochemistry, general staining, enzyme histochemistry, and visualization of fluorescent bone labels. We have consistently used tissues prepared in this manner for immunohistochemical demonstration of neuropeptides in skeletal tissues and for localizing tartrate-resistant acid phosphatase (TRAP). In addition, other tissues obtained from PVP-perfused rats, such as brain, spinal cord, muscle, gut, and sympathetic ganglia, are also well preserved and demonstrate immunohistochemical staining comparable to and possibly superior to that obtained with normal fixation protocols.

Animals↗