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Biomedical subjects

C Price

Publications and source records attributed to C Price.

At least 55 records · Page 3Linked to original sources

Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats.

Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for repeated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CD) rats were administered MEL or vehicle by gavage on gestation days (gd) 6-19. MEL-treated groups received 1-, 10-, 100-, 150-, or 200-mg/kg body weight/day in the screening study (15 rats/group), and 50, 100, or 200 mg/kg/day in the definitive study (25 rats/group). In both studies, maternal food/water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20, both studies), maternal liver and gravid uterine weights, number of ovarian corpora lutea, conceptus survival, fetal sex, and fetal body weight were evaluated. Fetal morphological examination included external structures (both studies) as well as visceral and skeletal structures (definitive study). In the screening study, maternal serum levels of 17beta-estradiol, progesterone, prolactin, and luteinizing hormone were determined by radioimmunoassay, and mammary tissue was fixed, stained, and evaluated for percent glandular area within the fat pad. No maternal morbidity/mortality was found in either study. In the screening study, aversion to treatment (> or =100 mg/kg/day) and reduced maternal weight gain (> or =150 mg/kg/day) were noted, but reproductive/endocrine parameters and fetal development were not affected. In the definitive study, aversion to treatment was noted at > or =50 mg/kg/day, and mild sedation, reduced maternal food intake, and reduced body weight gain were found during initial treatment with 200 mg/kg/day. MEL had no effect on prenatal survival, fetal body weight, or incidences of fetal malformations/variations. Thus, in the definitive study, the maternal toxicity NOAEL and LOAEL were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was > or =200 mg/kg/day.

Animals↗

Once daily ceftriaxone and gentamicin for the treatment of febrile neutropenia.

AIMS: To evaluate the pharmacokinetics of once daily (OD) gentamicin and its effectiveness as part of an OD regimen for the empirical treatment of febrile neutropenia in children with cancer. SUBJECTS: 59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) with febrile neutropenia (neutrophil count < 0.5 x 10(9)/l) after chemotherapy. METHODS: Over one year, 113 febrile neutropenic episodes were treated empirically with an OD antibiotic regimen of ceftriaxone (80 mg/kg; maximum 4 g) and gentamicin (7 mg/kg; infused over 60 minutes, no maximum). The patients were assessed after 48 hours. RESULTS: 86 of the 113 episodes settled with the first line antibiotic regimen. In 29 episodes, blood cultures identified a causative bacterial pathogen; for 17 of these, the first line antibiotic regimen was adequate; in four episodes, although the episode settled, ceftriaxone was replaced by a more appropriate antibiotic and OD gentamicin was continued; in the remaining eight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseudomonas aeruginosa. In 27 episodes (24%), resolution was obtained by the empirical introduction of a second line regimen of ceftazidime and a glycopeptide antibiotic, and/or amphotericin. Gentamicin concentrations were measured in 110 episodes and they were all below the 24 hour line indicating that there was no need to change the dosing interval. In two episodes (2%), serum creatinine rose transiently by more than 50% of the baseline concentration. Although there was no vestibular toxicity, three of 30 children who underwent pure tone audiometry reported high frequency hearing loss in one ear. CONCLUSION: OD gentamicin can be used safely and effectively to treat febrile neutropenia in children with cancer. When used for a short period (< 5 days), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary.

Adolescent↗

Percutaneous cervical cordotomy for the control of pain in patients with pleural mesothelioma.

BACKGROUND: Severe chest pain is common in mesothelioma. Percutaneous cervical cordotomy, which interrupts the spinothalamic tract at the C1/C2 level causing contralateral loss of pain sensation, is particularly appropriate in mesothelioma as the tumour is unilateral and systemic analgesia may be ineffective and is limited by harmful side effects. METHOD: A retrospective review was performed to determine the effectiveness and complication rate of this procedure. RESULTS: Fifty two patients were using opioids prior to cordotomy. The median daily dose of morphine before and after cordotomy was 100 mg (range 0-1000 mg) and 20 mg (range 0-520 mg), respectively (p < 0.001). Forty three patients (83%) had a reduction in pain such that their dose of opioid could be at least halved. Twenty patients (38%) were able to stop completely. Recurrence of pain requiring an increase in opioid medication was recorded in 18 patients at a median time of nine weeks (range 0.7-26 weeks). Four patients developed mild weakness, two had troublesome dysaesthesia. The median time from cordotomy to death was 13 weeks (range 0.3-52 weeks). Six early deaths within two weeks of cordotomy occurred early in the series and reflect postoperative chest infection and poor selection as the patients were in the terminal stages of mesothelioma. CONCLUSIONS: Percutaneous cervical cordotomy is successful in treating pain from mesothelioma. There was a low complication rate in this series. Referral to a unit experienced in cordotomy is recommended as soon as pain from chest wall invasion is suspected.

Adult↗

Short-term influence of prednisone and phenobarbital on thyroid function in euthyroid dogs.

The short-term effects of prednisone and phenobarbital on serum total thyroxine (tT4), free thyroxine (fT4), and thyroid stimulating hormone (TSH) were evaluated in euthyroid dogs. Twenty-six beagles were randomly divided into 3 groups receiving, respectively, a placebo, prednisone (1.2 to 2 mg/kg body weight, per os, every 12 hours for 3 weeks), or phenobarbital (1.8 to 3 mg/kg body weight for 1 week, then 2.7 to 4.5 mg/kg body weight, per os, every 12 hours for 2 weeks). Blood samples taken over a 6-week period were assayed for serum tT4, fT4, and TSH. Phenobarbital therapy in our study did not affect serum tT4, fT4, or TSH concentrations. Prednisone therapy, however, significantly decreased serum tT4 and fT4, but did not affect serum TSH concentrations.

Animals↗

Changes in calcium homoeostasis in patients undergoing liver transplantation: effects of a single infusion of pamidronate administered pre-operatively.

Bone turnover, bone loss and fracture risk increase after liver transplantation. It has been postulated that peri-operative administration of a bisphosphonate might prevent bone loss and reduce fracture rate. We studied the effects of a single pre-operative dose of pamidronate on biochemical parameters of skeletal metabolism in the first month after liver transplantation. In a randomized, single-blind study, six of 12 patients with chronic liver disease received 60 mg of pamidronate intravenously on a single occasion 1-30 days before transplantation. Six other patients undergoing transplantation received no pamidronate. We measured serum calcium, phosphate, albumin, bone-specific alkaline phosphatase, plasma parathyroid hormone and tartrate-resistant acid phosphatase before pamidronate infusion and at frequent intervals during the first 30 post-operative days. In treated patients, plasma parathyroid hormone increased 12-fold over baseline values and remained elevated in comparison with baseline at days 26-30; serum calcium and phosphate fell significantly, returning to normal at around day 14 post-operatively. There were no significant changes in any parameter in the untreated group. No changes in bone formation or resorption markers were observed in either group. The large increase in plasma parathyroid hormone concentrations in the treated group is probably secondary to the fall in serum calcium. The magnitude of the increase is much greater than that seen after pamidronate infusion in other patient groups. The lack of change in, or correlation of, serum calcium and plasma parathyroid hormone in the untreated group suggests that additional factors release calcium from bone after liver transplantation, presumably by increasing bone resorption.

Adult↗

Semantic based concept differential retrieval & equivalence detection in clinical terms version 3 (Read Codes).

Modern clinical terminologies are required to provide a large corpus of concepts to cover the complexity of medicine. It is well recognised that sufficient scalability is likely to be achieved only with those schemes that can build post-coordinated constructs compositionally. Clinical Terms Version 3 (Read Codes) uses a system of templates to both express the semantic definition (atoms) of concepts and to allow qualification of core concepts with additional detail. This common mechanism for expressing both intrinsic semantic information and additional information allows both pre- and post-coordinated concepts to be retrieved from different perspectives and to detect equivalence between alternative representations of the same concept. The practical application and experience of such an approach is described in relation to a live clinical database (Diabeta). The merits of such an approach are outlined and its relationship to other documented mechanisms outlined.

Classification↗

Segmenting healthcare terminology users: a strategic approach to large scale evolutionary development.

Healthcare terminologies have become larger and more complex, aiming to support a diverse range of functions across the whole spectrum of healthcare activity. Prioritization of development, implementation and evaluation can be achieved by regarding the "terminology" as an integrated system of content-based and functional components. Matching these components to target segments within the healthcare community, supports a strategic approach to evolutionary development and provides essential product differentiation to enable terminology providers and systems suppliers to focus on end-user requirements.

Delivery of Health Care↗

Telomerase expression in chickens: constitutive activity in somatic tissues and down-regulation in culture.

Although human and rodent telomeres have been studied extensively, very little is known about telomere dynamics in other vertebrates. Moreover, our current dependence on mice as a model for human tumorigenesis and aging poses a problem because human and mouse telomere biology is very different. To explore whether chickens might provide a more useful model, we have examined telomerase activity and telomere length in chicken tissues as well as in primary cell cultures. Although chicken telomeres resemble human telomeres in that they are 8-20 kb in length, the distribution of telomerase activity in chickens resembles what is found in mice. Active enzyme is present in germline tissue as well as in a wide range of somatic tissues. Because chicken cells exhibit extremely low rates of spontaneous immortalization, this finding indicates that constitutive telomerase expression does not necessarily lead to an increased immortalization frequency. Finally, we found that telomerase activity is greatly down-regulated when primary cultures are established from chicken embryos. Although this down-regulation explains the telomere loss and replicative senescence that we observed in fibroblast cultures, it raises questions concerning how relevant studies of senescence in primary cell cultures are to aging in whole animals.

Animals↗

A multimodal language region in the ventral visual pathway.

Reading words and naming pictures involves the association of visual stimuli with phonological and semantic knowledge. Damage to a region of the brain in the left basal posterior temporal lobe (BA37), which is strategically situated between the visual cortex and the more anterior temporal cortex, leads to reading and naming deficits. Additional evidence implicating this region in linguistic processing comes from functional neuroimaging studies of reading in normal subjects and subjects with developmental dyslexia. Here we test whether the visual component of reading is essential for activation of BA37 by comparing cortical activations elicited by word processing in congenitally blind, late-blind and sighted subjects using functional neuroimaging. Despite the different modalities used (visual and tactile), all groups of subjects showed a common activation of BA37 by words relative to non-word letter-strings. These findings agree with the proposal that BA37 is an association area that integrates converging inputs from many regions. Our study confirms a prediction of theories of brain function that depend on convergence zones; the absence of one input (that is, visual) does not alter the response properties of such a convergence region.

Adult↗

Lymphopain, a cytotoxic T and natural killer cell-associated cysteine proteinase.

Through differential screening of established human leukaemia cell lines, we have identified and molecularly cloned lymphopain, a novel cysteine proteinase of the papain family. Lymphopain exhibits a remarkably restricted cellular pattern of expression, being predominantly expressed in cytotoxic T-lymphocytes and natural killer cells. The human lymphopain locus maps to chromosome 11q13, encodes a polypeptide of 376 amino acids and is conserved in the mouse. Both human and murine forms appear more closely related to protozoan papain-like enzymes than to other mammalian members of the papain family. The cellular distribution of lymphopain expression, together with the functional demonstration of lymphopain-associated proteinase activity in vitro, is suggestive of a role for lymphopain in immune cell-mediated, cell killing.

Amino Acid Sequence↗

Regional analgesia in early active labour: combined spinal epidural vs. epidural.

We randomly allocated 93 women in early active labour and requesting epidural analgesia to receive either epidural (n = 48) or combined spinal-epidural analgesia (n = 45). For epidural analgesia 15 ml of bupivacaine 0.1% with 75 micrograms of fentanyl were injected into the epidural space. For combined spinal-epidural analgesia 1 ml of bupivacaine 0.25% with 25 micrograms of fentanyl were injected into the subarachnoid space. For both groups subsequent top-ups of 10 ml of bupivacaine 0.1% with fentanyl 20 micrograms were given using a lightweight patient-controlled epidural analgesia (PCEA) pump with a lockout time of 30 min. We assessed analgesia and the degree of motor blockade and found no significant differences in pain or maternal satisfaction scores between the two groups. The time to first top-up was significantly longer in the epidural group than in the CSE group (p = 0.01). The combined spinal-epidural group had significantly greater motor blockade at 30 min than the epidural group (p = 0.01), but there was no difference after this. The PCEA machine failed completely twice and temporarily many times. We conclude that the combined spinal-epidural technique confers no advantages in early active labour. Also, a lightweight PCEA pump needs to be more reliable before we can recommend its use.

Adult↗

Dual-task results and the lateralization of spatial orientation: artifact of test selection?

An investigation was conducted to identify the degree to which results regarding the lateralization of spatial orientation among men and women are artifacts of test selection. A dual-task design was used to study possible lateralization differences, providing baseline and dual-task measures of spatial-orientation performance, right- and left-hand tapping, and vocalization of "cat, dog, horse." The Guilford-Zimmerman Test (Guilford & Zimmerman, 1953), the Eliot-Price Test (Eliot & Price, 1976), and the Stumpf-Fay Cube Perspectives Test (Stumpf & Fay, 1983) were the three spatial-orientation tests used to investigate possible artifacts of test selection. Twenty-eight right-handed male and 39 right-handed female undergraduates completed random baseline and dual-task sessions. Analyses indicated no significant sex-related differences in spatial-orientation ability for all three tests. Furthermore, there was no evidence of differential lateralization of spatial orientation between the sexes.

Adult↗

Different activation patterns in the visual cortex of late and congenitally blind subjects.

A key issue in developmental neuroscience is the role of activity-dependent mechanisms in the epigenetic induction of functional organization in visual cortex. Ocular blindness and ensuing visual deprivation is one of the rare models available for the investigation of experience-dependent cortical reorganization in man. In a PET study we demonstrate that congenitally blind subjects show task-specific activation of extrastriate visual areas and parietal association areas during Braille reading, compared with auditory word processing. In contrast, blind subjects who lost their sight after puberty show additional activation in the primary visual cortex with the same tasks. Studies in blind-raised monkeys show that crossmodal responses in extrastriate areas can be elicited by somatosensory stimulation. This is consistent with the crossmodal extrastriate activations elicited by tactile processing in our congenitally blind subjects. Since primary visual cortex does not show crossmodal responses in primate studies, the differential activation in late and congenitally blind subjects highlights the possibility of reciprocal activation by visual imagery in subjects with early visual experience.

Adult↗