Biomedical subjects
Publications and source records attributed to M Hill.
The authors discuss neuropathic osteoarthropathy in the diabetic foot, often associated with Charcot joints. Identification of this malady as well as indications for treatment are reviewed. Representative cases are illustrated.
Serum hyaluronan levels are increased in dialysis patients. We evaluated several factors that influence serum hyaluronan levels in 184 patients on chronic hemodialysis (duration 2.3 +/- 2.3 [SD] years). The levels were higher than normal in the whole group and in a subgroup of 133 patients without chronic infection, liver disease, or rheumatoid arthritis (215 +/- 19 and 205 +/- 22 microg/L, respectively). There was a tendency for the levels to be higher in a subgroup of patients with hepatitis c virus (HCV) infection. There was no correlation between hyaluronan levels, alanine aminotransferase (ALT), and duration or dose of dialysis. A weak but highly significant negative correlation between serum albumin levels and serum hyaluronan and ferritin levels was seen. The data suggest that chronic inflammation may explain, at least in part, the increased hyaluronan levels found in chronic dialysis patients.
Although the desired outcome for undergraduate research curricula is to produce informed consumers/critiquers of research, baccalaureate students often have difficulty linking research concepts with clinical practice. The authors describe an innovative approach to integrating research content with a clinical experience through use of student teams working with practicing nursing preceptors to identify and study research problems.
Social factors play a major role in determining the impact of epilepsy on families. This paper reviews the literature on the needs of families and their social networks, and services proposed for them. The predominantly negative picture presented in the 'expert' literature is compared with the more positive one presented in first-hand studies of families' views and in the literature on children with other disabilities. The implications of these differing perspectives for service provision are discussed.
Although protein tyrosine kinases (PTKs) have been implicated in late preconditioning (PC) against infarction, their role in late PC against stunning is unknown. Furthermore, it is unknown whether PTK signaling is necessary only to trigger late PC on day 1 or also to mediate it on day 2. Thus, conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days (days 1, 2, and 3). In the control group (group I, n=7), the recovery of systolic wall thickening after the 6 occlusion/reperfusion cycles was markedly improved on days 2 and 3 compared with day 1, indicating the development of late PC against stunning. Administration of the PTK inhibitor lavendustin-A (LD-A, 1 mg/kg IV) before the first occlusion on day 1 (group II, n=7) completely prevented the late PC effect against stunning on day 2. Late PC against stunning was also abrogated when LD-A was given before the first occlusion on day 2 (group III, n=7); however, in these rabbits, the late PC effect became apparent on day 3, indicating that LD-A itself did not have any delayed deleterious actions on myocardial stunning. In group V (n=5), the sequence of 6 occlusion/reperfusion cycles resulted in a robust increase in the activity of inducible NO synthase (iNOS [assessed as Ca(2+)-independent L-citrulline formation]) and nitrite+nitrate (NO(x)) tissue levels 24 hours later (on day 2), with no concomitant change in Ca(2+)-dependent NO synthase (endothelial NO synthase and/or neuronal NO synthase) activity. Similar results were obtained on day 3 (group VIII, n=6), indicating sustained upregulation of iNOS. Administration of LD-A either on day 1 (group VI, n=5) or on day 2 (group VII, n=6) abrogated the increase in iNOS activity and NO(x) levels on day 2. LD-A had no effect on iNOS activity or NO(x) levels in the absence of PC (group X, n=5). This study demonstrates that in conscious rabbits, PTK activity is necessary not only to trigger late PC against stunning on day 1 but also to mediate the protection on day 2. This investigation also provides the first direct evidence that cardiac iNOS activity is upregulated during the late phase of ischemic PC in rabbits. Furthermore, the data indicate that PTK signaling is essential for the augmentation of iNOS activity and that PTKs modulate this enzyme at two distinct levels: at an early stage on day 1 and at a late stage on day 2. This bifunctional role of PTKs in late PC has broad implications for the signaling mechanisms that underlie the response of the heart to ischemic stress and, possibly, other stresses.
Explore the source record for details and available documents.
BACKGROUND: The purpose of this study was to determine the level of visual acuity following occlusion treatment for strabismic and anisometropic amblyopia and to analyze the factors that influence the outcome. METHODS: In this observational study, we examined the medical records of 246 patients discharged between April 1991 and March 1996, including those who failed to complete treatment. Two groups were identified: Group 1 esotropia (n = 151); and Group 2 anisometropic amblyopia with or without microtropia (n = 79). Factors influencing outcome of treatment were analyzed, success being defined as 6/12 or better in the amblyopic eye. RESULTS: In Group 1, 85% achieved 6/12 or better in the worst eye (linear acuity test), 15% achieved less than 6/12. (73% achieved 6/9 or better, 16% achieved 6/12 or 6/18, and 11% achieved less than 6/18). In group 2, 95% achieved 6/9 or better in the worst eye (linear acuity test); 5% achieved 6/12. CONCLUSION: Outcome was better than other full population studies to date. A good visual outcome was achieved in all cases of pure anisometropic amblyopia. Significant factors influencing outcome in the esotropic group were compliance, anisometropia, and visual acuity at start of treatment. An occlusion protocol is suggested aimed at further improving compliance and outcome.
A retrospective radiographic study was undertaken to determine the incidence of a bipartite tibial sesamoid and its relationship in hallux abducto valgus (HAV) deformity. It was found that the incidence of a bipartite tibial sesamoid associated with HAV deformity was twice as frequent than a bipartite tibial sesamoid in a general foot population. The authors conclude that the tibial sesamoid plays an important role in the development of HAV deformity.
Human papillomavirus type 33 (HPV33) belongs to the group of HPV types frequently found in severe cervical dysplasias and carcinomas. By analogy with HPV types 16 and 18 selectively expressing E6 and E7 genes in malignant tissues, we studied the HPV33 E6 and E7 open reading frames in various configurations with upstream promoter and noncoding region (NCR) known to contain a particular 78-bp tandem repeat. HPV DNA fragments were cloned into expression vectors between the SV40 or the mouse metallothionein I promoter and the neo gene, transfected into NIH3T3 cells, selected by neo resistance, and inoculated into nude mice. In these bioassays, a weak transforming activity was detected for E6 open reading frame, and could be significantly enhanced either by the NCR or the E7 open reading frame. No tumorigenicity could be detected for E7 alone or in configuration with the upstream NCR. Further analyses of tumor cells showed that HPV33-derived genes were not sufficient to induce an anchorage-independent phenotype and, interstingly, there was no requirement for virus-transfected tumor cells to retain HPV sequences during tumor progression. We concluded that the transformation function of HPV33 resides in E6 gene as assayed by tumorigenicity. An enhancer of the E6 promoter is located in the NCR. On the other hand, in the absence of the NCR, E6 tumorigenicity may be augmented by the E7.
The calcium channel blocker nifedipine was administered to pregnant sheep by a four-level iv infusion at rates of 1-10 micrograms/kg/min. The maternal and fetal plasma nifedipine concentrations were measured along with maternal and fetal heart rate, blood pressure, pH, and blood gases. The two-compartment maternal pharmacokinetics demonstrated a rapid phase t1/2 of 11 min and a slower phase t 1/2 of 137 min. The drug reached the fetus via a first-order process with a t 1/2 of 22 min. At the highest dose, the maternal systemic vascular resistance dropped 49% in association with a 59% increase in heart rate. The uterine blood flow decreased 29%. Tachycardia was the only significant effect in the fetus. In a subgroup of sheep, chronic dosing with phenobarbital increased maternal nifedipine clearance 3-fold.
The oncornaviruses share several biological, biochemical, and structural properties that distinguish them from other RNA viruses. Rous sarcoma virus, a representative of avian oncornaviruses, manifests two major functions: cell transformation and virus replication. Both functions are independent, and are expressed separately in defective viruses. The virus has a 60-70S RNA, composed of 35 S subunits. It appears that each subunit of viral RNA carries the same genetic information and, furthermore, that 10% of this information is coding for cell transformation. Without this 10% the virus can still replicate. The RNA genome is expressed when the virus penetrates a sensitive cell, provided the virus carries an active reverse transcriptase. Virus-transformed cells possess a DNA form of the viral genome. The viral DNA is infectious, and can lead, upon transfection of permissive cells, to the production of a new viral progeny. We have established that the minimum molecular weight of the viral DNA is 6 X 10(6) daltons, and that this DNA is covalently bound to the chromosomal DNA. Also by examining the frequency of transfection events in the DNA-treated cells we suggest that transfection is a single-hit phenomenon. It follows that viral DNA of 6 X 10(6) daltons carries all the genetic information to code for the virus production. It seems likely that the transfection mechanism giving rise to transforming viruses is different from that producing nontransforming segments. In general terms, the experimental data indicate that certain RNAs and DNAs could accomplish malignant transformation if they are able to penetrate into the cell and give rise to the DNA forms which could be integrated into the cellular genome.
A selection procedure is described for obtaining cell variants, called autotrophs, which are able to grow from low-molecular-weight metabolic precursors in the absence of macromolecules and serum replacement factors. These autotrophs can readily be isolated from a variety of cell lines, including normal (nontransformed) NIH3T3 cells, their spontaneous or tre oncogene-transfected tumor-producing derivatives, and HeLa cells. Tre-transfected autotrophs grew faster than their normal or spontaneously transformed counterparts, and much faster than autotrophic HeLa cells. Chinese hamster autotrophs, which have now been cultured for nearly two years, grow with a population doubling time of 30 h.
Methionine has been successfully used to control tumor progression in vivo and to induce reversions of transformed cells in vitro. In the present study, we measured mutations at the HGPRT locus of RSV-transformed cells serially propagated in methionine-supplemented medium and assayed at each passage for thioguanine resistance. The frequency of spontaneous mutants at this locus was 7.2 X 10(-5); this value gradually increased during the methionine treatment to as much as 9.2 X 10(-4), and returned to initial values when the methionine treatment was withdrawn. It is proposed that the mutants were induced by the methionine derivative, S-adenosylmethionine, and the resulting mutant frequency determined by equilibrium between mutagenic action of this metabolite and DNA repair.
Serially propagated fibroblast clones were treated with 25-mM methionine and a thioguanine resistance assay was performed at each passage to measure mutagenesis at the HGPRT locus. The spontaneous frequency of thioguanine resistant mutants before treatment was less than 5 X 10(-6) in four clones and 22 X 10(-6) in one clone. These values dropped 10- to 100-fold and remained so until the methionine was withdrawn, then returned to, or overshot, the initial values. It is proposed that these fibroblasts, unlike their previously described RSV-transformed counterparts, possess a repair enzyme capable of an adaptive response to S-adenosylmethionine, the metabolite thought to be responsible for methionine mutagenicity in vivo.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.