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R Hill

Publications and source records attributed to R Hill.

At least 343 records · Page 19Linked to original sources

Model systems and their predictive value in assessing teratogens.

For ethical and regulatory reasons all newly developed drugs are evaluated for safety in a series of preclinical animal toxicity studies. Prior to the 1960's there were no standardized procedures or regulatory guidelines for specifically examining the teratogenic potential of a compound, although an evaluation of the overall effect on reproductive processes was recommended. Following the thalidomide saga, specific studies for evaluating teratogenicity were included in regulatory preclinical guidelines in most countries of the world. However, the level of confidence in the ability of these animal studies to be predictive for man remains far from high. Differences between model systems and man emphasize some of the reasons for the perceived low level of predictability of animal tests for man. Only when the mechanism of teratogenesis and the factors affecting species differences in teratogenic response are understood will we have confidence in the predictive accuracy of animal studies.

Animals↗

Effect of ethanol on (R)- and (S)-salsolinol, salsoline, and THP in the nucleus accumbens of AA and ANA rats.

Tetrahydroisoquinolines (TIQ) are active metabolites of dopamine. Intracerebral application stimulates the voluntary ethanol intake. In the present study, the levels of several TIQ's [(S)- and (R)-salsolinol, salsoline and tetrahydropapaveroline (THP)] were measured in the extracellular space of the nucleus accumbens of alcohol-preferring AA and alcohol-avoiding ANA rats. Ethanol (2 g/kg i.p.) caused an increase in dopamine levels in ANA but not in AA rats. Neither (R)- nor (S)-salsolinol concentrations changed after ethanol application, though (S)-salsolinol concentrations were higher in ANA than in AA rats. Ethanol caused an increase in salsoline concentrations in ANA but not in AA rats. THP increased following ethanol, which tended to be stronger in ANA rats. The study revealed differences in the TIQ levels of the nucleus accumbens between AA and ANA rats. In case of changes following ethanol application (dopamine, salsoline, THP), the AA rats were less sensitive. The findings resemble observations in high-risk sons of alcoholics with reduced sensitivity to ethanol in young age and increased risk to become alcoholic.

Alcoholism↗

The role of Bapx1 (Nkx3.2) in the development and evolution of the axial skeleton.

The bagpipe-related homeobox-containing genes are members of the NK family, bagpipe (bap) was first identified in Drosophila and there are three different bagpipe-related genes in vertebrates. Only two of these are found in mammals, the Nkx3.1 and the Bapxl (Nkx3.2) gene. The targeted mutation in the mouse Bapxl gene shows a vertebral phenotype in which the ventromedial elements are lacking; these are the centra and the intervertebral discs. In addition, a region of gastric mesenchyme is abnormal. This mesenchyme surrounds the posterior region of the presumptive stomach and duodenum, and in the mutant fails to support normal development of the spleen. In Drosophila, bagpipe has a role in gut mesoderm and the mutant embryos have no midgut musculature. Thus bap related genes in mouse and Drosophila have roles in patterning gut mesoderm; however, neither of the mammalian genes has a discernible role in the gut musculature. In contrast, both mammalian genes have roles in developmental processes that have appeared recently in evolution. The Bapxl gene found in fish, amphibians, birds and mammals appears to have derived vertebrate specific functions sometime after the split between the jawless fish and gnathostomes.

Animals↗

Effect of energy repletion on dynamic aspects of protein metabolism of malnourished adolescent and young adult patients with cystic fibrosis during the first 12 days of treatment.

The short-term effect of nutritional rehabilitation on whole body protein metabolism of six malnourished (energy depleted) adolescent and young adult cystic fibrosis (CF) patients was examined during the first 12 days of treatment. Refeeding was accomplished using continuous nasogastric administration of an elemental diet. Intakes were 1.65 SD 0.3 g protein/kg/day and 85.3 SD 19.2 kcal/kg/day. Turnover measurements were carried out on four occasions, during the control period on a normal diet and days 4, 8, and 12 on the elemental diet. In response to refeeding, whole body amino nitrogen flux (Q) fell consistently over the study (p less than 0.05). Protein synthesis (S) and breakdown (B) also fell but their values did not reach statistical significance. On the other hand, there was a prompt increase in ratios S/Q and B/Q in response to tube feeding discernible on days 4 and 8 (p less than 0.05), but which returned to baseline by day 12. We conclude that malnourished CF patients who are still eating well have increased rates of protein turnover. There is a prompt response of protein metabolism to energy repletion with a progressive decline in rates during the first 12 days of treatment.

Adolescent↗

The effects of gaviscon and metoclopramide in gastroesophageal reflux in children.

Oral metoclopramide (0.5 mg/kg/24 h) and a liquid alginic acid-antacid compound were administered to infants and children with gastroesophageal reflux (GER) in a double-blind randomized controlled trial. The effect of medication was measured with 24-h intraesophageal pH monitoring. Neither metoclopramide nor the alginic acid-antacid compound decreased the frequency or duration of gastroesophageal reflux.

Adolescent↗

Look, learn, and be satisfied: video playback as a learning strategy to improve clinical skills performance.

The study investigated the viability of video playback as a means to maintain and enhance nursing skills in today's healthcare environment. The purpose was to determine if video playback would improve performance of psychomotor clinical skills and increase participant satisfaction with the leaning process. A two-group sample of registered and student nurses participated in the study. Each participant performed a nursing procedure. Two nursing procedures were used, one for each group. Each nursing procedure was recorded on videotape and played back to the participant who then repeated the procedure and completed a satisfaction assessment questionnaire. Results showed improved performance and learner satisfaction.

Adult↗

Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD), a familial cardiomyopathy occurring with a prevalence of 1 in 5000, is characterized by replacement of myocytes with fatty and fibrous tissue. Clinical manifestations include structural and functional abnormalities of the right ventricle and arrhythmias, leading to a sudden death rate of 2.5% per year. Four loci have been mapped, but no gene has been identified as yet. METHODS AND RESULTS: We identified a large family of >200 members with ARVD segregating as an autosomal dominant trait affecting 10 living individuals. The diagnosis of ARVD was based on international diagnostic criteria including history, physical examination, ECG, echocardiogram, right ventricular angiogram, endomyocardial biopsy, and 24-hour ambulatory ECG. Blood was collected for DNA from 149 family members. Analysis of 257 polymorphic microsatellite markers by genetic linkage excluded previously known loci for ARVD and identified a novel locus at 3p23. Analysis of an additional 20 markers further defined the region. A peak logarithm of the odds score of 6.91 was obtained with marker D3S3613 at theta=0% recombination. Haplotype analysis identified a shared region between markers D3S3610 and D3S3659 of 9. 3 cM. CONCLUSIONS: A novel locus for ARVD has been mapped to 3p23 and the region narrowed to 9.3 cM. Identification of the gene will allow genetic screening and a specific diagnosis for a disease with protean nonspecific findings. It should also provide insight fundamental to understanding cardiac chamber-specific gene expression and/or the mechanism of myocyte apoptosis observed in this disease.

Adult↗

In vitro and in vivo performance of porcine islets encapsulated in interfacially photopolymerized poly(ethylene glycol) diacrylate membranes.

The usefulness of interfacial photopolymerization of poly(ethylene glycol) (PEG) diacrylate at a variety of concentrations and molecular weights to form hydrogel membranes for encapsulating porcine islets of Langerhans was investigated. The results from this study show in vitro and in vivo function of PEG-encapsulated porcine islets and the ability of PEG membranes to prevent immune rejection in a discordant xenograft model. Encapsulated islets demonstrated an average viability of 85% during the first week after encapsulation, slightly but significantly lower than unencapsulated controls. Encapsulated porcine islets were shown to be glucose responsive using static glucose stimulation and perifusion assays. Higher rates of insulin release were observed for porcine islets encapsulated in lower concentrations of PEG diacrylate (10-13%), not significantly reduced relative to unencapsulated controls, than were observed in islets encapsulated in higher concentrations (25%) of PEG diacrylate. Perifusion results showed biphasic insulin release from encapsulated islets in response to glucose stimulation. Streptozotocin-induced diabetic athymic mice maintained normoglycemia for up to 110 days after the implantation of 5,000-8,000 encapsulated porcine islet equivalents into the peritoneal cavity. Normoglycemia was also confirmed in these animals using glucose tolerance tests. PEG diacrylate-encapsulated porcine islets were shown to be viable and contain insulin after 30 days in the peritoneal cavity of Sprague-Dawley rats, a discordant xenograft model. From these studies, we conclude that PEG diacrylate encapsulation of porcine islets by interfacial photopolymerization shows promise for use as a method of xenoprotection toward a bioartificial endocrine pancreas.

Animals↗

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Architectural Accessibility↗

The integration of inpatient treatment and transitional day hospital: application of a problem-solving approach.

Because of the trend in inpatient psychiatry toward a marked decrease in length of hospitalization, clinicians must reconceptualize the manner in which psychosocial treatments are organized in the inpatient milieu. Considerable data suggest that problem-solving therapies may be a productive way to integrate the groups and activities in the therapeutic milieu. This paper describes the application of a problem-solving approach to the therapeutic milieu and indicates that the therapeutic gains from this approach may be enhanced by combining inpatient treatment with a transitional day hospital program. We identify the empirical underpinnings of this model and describe how it has been used to treat a schizophrenic patient. We suggest that problem-solving therapies are effective for promoting behavioral change on the general psychiatric inpatient unit.

Adult↗

Paramedic interpretation of prehospital lead-II ST-segments.

OBJECTIVE: To determine the reliability of ST-segment interpretation by paramedics from lead-II rhythm strips obtained in the prehospital setting. DESIGN: Prospective, blinded study of 127 patients transported by an urban/rural emergency medical services system with complaints consistent with ischemic heart disease. METHODS: Emergency department physicians asked emergency medical technician-paramedics (EMT-P) via radio to evaluate ST-segments for elevation or depression and grade it as "mild," "moderate," or "severe." Then, this rhythm strip was interpreted blindly by emergency physicians who also interpreted the lead-II obtained from a 12-lead electrocardiogram (ECG) obtained in the emergency department (ED). The field interpretation was compared with the subsequent readings and the final in-patient diagnosis using positive predictive value (PPV), negative predictive value (NPV), and the Kappa statistic. Markedly discrepant interpretations were analyzed separately. RESULTS: Using physician interpretation as the reference standard, paramedic interpretation of the lead-II ST-segments obtained in the prehospital setting was correct (within +/- 1 gradation) in 113 out of 127 total cases (89%). Of 105 patients for whom final hospital diagnosis was available, the ST-segment on the rhythm strip obtained in the prehospital setting, had a positive predictive value of 74% and a negative predictive value of 85% for myocardial ischemia or myocardial infarction (MI) (p < 0.001, Kappa = 0.59). Discordant interpretations between the paramedics and emergency physicians often were related to a basic misunderstanding of rhythm strip morphology. CONCLUSION: Field interpretation of ST-segments by paramedics is fairly accurate as judged both by emergency physicians and correlation with final patient outcome, but its clinical utility is unproved. A small but clinically significant number of outliers, consisting of markedly discrepant false positives, reflects paramedic uncertainty in identifying the deviations of the ST-segment.

Adult↗

Chromosomal abnormalities and gene amplification in renal cancers induced in rats by nickel subsulfide.

Nickel subsulfide (alpha Ni3S2) was administered to male Fischer-344 rats by unilateral intrarenal (i.r.) injection (20 mg per rat) to establish the time-course of alpha Ni3S2-induced erythrocytosis and to identify chromosomal abnormalities and molecular genetic aberrations in ensuing renal cancers. Blood hematocrit values were increased in alpha Ni3S2-treated rats during two to 36 weeks post-injection, attained a maximum of 77 percent (SD +/- 5) at 16 weeks (vs 51 +/- 3 percent in vehicle controls), and returned to baseline at 40 weeks. Within 21 months, malignant neoplasms (five sarcomas, one carcinoma) occurred in the injected kidneys of 6/28 alpha Ni3S2-treated rats (vs 0/13 controls). Cytogenetic analyses of direct preparations or primary cell cultures showed prominent chromosomal aberrations in three neoplasms, with rearranged marker chromosomes, polyploidy, and in one case an homogeneously staining region (HSR). Assays for gene amplification were performed with probes for murine erythropoietin (EPO) gene and H-ras, c-fos, c-myc, and N-myc oncogenes, using deoxyribonucleic acid (DNA) samples isolated from injected kidneys and renal neoplasms, as well as from the contralateral, non-injected kidneys. No consistent pattern was found; in one sarcoma, N-myc was amplified six-fold and c-fos was amplified two-fold; in another sarcoma, H-ras, c-fos, and EPO were amplified two-fold. This study shows that (a) karyotypes of 3/6 renal neoplasms of alpha Ni3S2-treated rats contained prominent marker chromosomes, (b) oncogene amplification was noted in 2/6 renal neoplasms, and (c) the EPO gene was not consistently amplified in DNA from the injected kidneys of alpha Ni3S2-treated rats during the initiation of erythrocytosis, or in subsequent renal neoplasms.

Animals↗

Opacification of epidural venous plexus and dura in evaluation of cervical nerve roots: CT technique.

Thin-section computed tomography (CT) after bolus high-volume, intravenous contrast enhancement of the cervical epidural and intervertebral foraminal venous plexus was undertaken in eight patients. Visualization of exiting cervical nerve root by opacification of the surrounding intervertebral plexus was evaluated in 38 foramina. Visualization was judged as excellent in 77% and good in 21%. Thus the nerves were seen satisfactorily in all but one foramen. As the CT scan parallels the long axis of the cervical roots as they pass through the intervertebral foramen, anatomic delineation of the root out to the level of the vertebral artery is excellent. A local widening of the root, which was thought to represent the dorsal root ganglion, was seen in most foramina examined. Excellent filling of the epidural plexus was seen in seven of eight subjects; good opacification was seen in the other subject. In no instance did the study fail to satisfactorily fill the epidural plexus in the cervical vertebral canal. This technique appears to be an excellent method for evaluating the cervical nerve roots and the epidural space.

Cervical Plexus↗

Seminal plasma biochemistry. I. Preliminary report: a possible mechanism for the liquefaction of human seminal plasma and its relationship to spermatozoal motility.

Based on indirect evidence it has been suggested that the liquefaction of human seminal plasma involves fibrinolytic and proteolytic enzymes and that the coagulum is formed by proteins. In this preliminary investigation evidence is presented for the involvement of seminal plasma sialyltransferase in liquefaction which suggests that the coagulum may be composed of glycoproteins. It is proposed that the glycoproteins form a polymer by the chelation of divalent metal ions via the carboxylic acid moieties of the sialic acid groups of the glycoproteins. The glycoprotein polymer may then be dismantled by the reduction of the meal ions by the oxidation of L-ascorbic acid, possibly allowing enzymes to complete the liquefaction process. A total of 100 semen samples from 30 male subjects whose semen profiles were considered "normal" by an independent assessor, were examined for the following: (i) liquefaction time of the seminal plasma; (ii) seminal plasma sialyltransferase activity; (iii) spermatozoal motility, defined as directional or nondirectional; (iv) spermatozoal count, and (v) seminal plasma content of free L-ascorbic acid, dehydroascorbic acid and glutathione. Linear regression analysis showed a significant correlation between sialyltransferase activity and the liquefaction time for seminal plasma. Similarly, multilinear regression analysis of the data showed that as the seminal plasma levels of L-ascorbic acid, total dehydroascorbic acid and glutathione increase, there is a decrease in spermatozoal motility and a decrease in the liquefaction time of the seminal plasma. The possible metabolic relationship of seminal plasma L-ascorbic acid and glutathione is discussed and a metabolic pathway is suggested.

Ascorbic Acid↗