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Biomedical subjects

C Roberts

Publications and source records attributed to C Roberts.

At least 163 records · Page 9Linked to original sources

Prior anterior cruciate ligament reconstruction complicating intramedullary nailing of a tibia fracture.

As the number of patients with anterior cruciate ligament reconstructions continues to grow, a subpopulation of patients with displaced tibia-fibula fractures will emerge who have had prior anterior cruciate ligament reconstructions. Previous cruciate ligament surgery can complicate the operative treatment of tibia-fibula fractures by intramedullary nailing. Technical complications arise because the tibial tunnel-graft-screw is in the path of insertion of the intramedullary implant. We present a case in which we traced the path of the patellar tendon autograft, adjusted our entry point for the tibial intramedullary canal, and removed the interference screw to facilitate the fracture surgery. This technical note provides an approach to planning intramedullary nailing of the tibia in patients with prior anterior cruciate ligament surgery.

Adult↗

HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3.

HIRA maps to the DiGeorge/velocardiofacial syndrome critical region (DGCR) at 22q11 (refs 1,2) and encodes a WD40 repeat protein similar to yeast Hir1p and Hir2p. These transcriptional co-repressors regulate cell cycle-dependent histone gene transcription, possibly by remodelling local chromatin structure. We report an interaction between HIRA and the transcription factor Pax3. Pax3 haploinsufficiency results in the mouse splotch and human Waardenburg syndrome (WSI and WSIII) phenotypes. Mice homozygous for Pax3 mutations die in utero with a phenocopy of DGS, or neonatally with neural tube defects. HIRA was also found to interact with core histones. Thus, altered stoichiometry of complexes containing HIRA may be important for the development of structures affected in WS and DGS.

Animals↗

Erythrocyte insulin-like growth factor-L binding in younger and older males.

OBJECTIVE: Insulin-like growth factor-1 (IGF-l) levels are lower in older compared with younger subjects. We tested the hypothesis that the reduction in circulating IGF-l would be accompanied by upregulation in tissue IGF-l binding in at least some tissues. We tested erythrocyte IGF-l binding since blood is an accessible tissue in humans, and there is growing evidence to suggest that erythrocyte IGF-l binding is influenced by circulating IGF-l. DESIGN AND PATIENTS: We compared 9 healthy older males (61-68 years old) with 9 healthy younger males (15-19 years old). MEASUREMENTS: Standard techniques were used to assay circulating IGF-l and IGF binding proteins 1-5 (IGFBPs 1-5). Erythrocyte IGF-l binding was first measured by studies in which native [125l]-IGF-l was displaced with unlabelled native IGF-l. In order to determine a possible role for IGF binding proteins (IGFBP), native [125l]-IGF-l was displaced with des-(1-3)IGF-1, which binds with IGF receptors but not IGFBPs. RESULTS: As expected, circulating IGF-l was significantly lower in the older compared with the younger subjects. In addition, IGFBP-3 and 5 were significantly lower, and IGFBP-4 higher, in older compared with younger subjects. When native [125l]-IGF-l was displaced with unlabelled native IGF-l, the number of IGF-l binding sites per erythrocyte was higher in the older subjects (43 +/- 5 vs. 18 +/- 2, older vs. younger, respectively; P < 0.05). In contrast, when native [125l]-IGF-l was displaced with des-(1-3), IGF-l binding capacity was not different between the two age groups. CONCLUSIONS: Erythrocyte IGF binding was increased in older compared with younger subjects. Surprisingly, the mechanism of the increase may not be a simple up regulation of IGF-l receptors in response to reduced circulating IGF-l, but possibly by an increase in the levels of as yet unidentified erythrocyte membrane-associated IGF binding proteins.

Adolescent↗

General practitioners and the Internet: modelling a 'virtual community'.

BACKGROUND: Electronic discussion lists are used by many groups, including GPs, for communication and information sharing. The technology offers potential for formal learning and professional development. Various models have been proposed to describe the dynamics of such 'virtual' forums, and research is required to explore how such a discussion list might support professional development. OBJECTIVE: We aimed to explore the use of the Internet-based discussion group gp-uk by GPs and their colleagues. METHODS: We carried out a qualitative study of the electronic text generated by GPs and colleagues on an academic medical discussion group. RESULTS: The list gp-uk has features of a collaborative medium, in which the audience are also contributors. There is support for a 'critical mass' model, in which a relatively small number of members contribute on a regular basis. There is little support for a 'discretionary database' model of more formal sharing of specific factual information. CONCLUSIONS: The findings indicate a model for a 'virtual classroom' for computer-mediated learning and professional development. A critical mass of participants is a requisite, the list should be facilitated to guide discussions and supporting resources such as an Internet web-site should be provided.

Computer Communication Networks↗

Can a clinical score aid in early diagnosis and treatment of various stroke syndromes?

BACKGROUND: Accurate and timely diagnosis of hemorrhagic and nonhemorrhagic strokes helps in patient management. Neuroimaging studies are useful in diagnosis and distinction of hemorrhagic (HS) and nonhemorrhagic (NHS) strokes. The use of clinical variables, such as Siriraj stroke scores (SSS), has shown good sensitivity, specificity and predictive values (distinguishing stroke types). The aim of our study was to evaluate the use of SSS in a U.S. population and assess whether it could aid to expedite treatment decisions. METHODS: Levels of consciousness, vomiting, headache and atheroma markers used in SSS were applied to patients who met the criteria for stroke. RESULTS: Of the 302 patients identified, the SSS classified 254 with sensitivity of 36% (HS) and 90% (NHS) and positive predictive values of 77% and 61%, respectively. CONCLUSION: Our results suggest that SSS is not reliable in distinguishing stroke types (in a US population). Definite neuroimaging studies are needed prior to thrombolytic therapy.

Aged↗

The growth and development of a research study: why stroke survivors wait so long.

The recent focus on stroke treatment has revealed that stroke survivors are not reaching emergency care early enough to benefit from available treatment modalities. As a result, the authors designed a study to determine the factors that influence the timing of seeking health care for stroke symptoms. Encouraged and supported by peers across the country, it became a collaborative national multicenter research study. This article describes the process used to develop the research study, as well as the challenges encountered along the way.

Cerebrovascular Disorders↗

Vascular compromise and amputation after intramedullary nailing of a tibia fracture.

A case is presented of a fifty-three-year-old man with a displaced tibia-fibula fracture that was treated with an intramedullary nail. The morning after surgery pulses were absent and did not improve after fasciotomies. The patient was transferred to our institution, where an arteriogram showed tapering of the anterior tibial and peroneal vessels in the mid-calf and occlusion of the posterior tibial artery at the level of the ankle. Vascular status did not improve after heparinization and arteriogram thrombolysis. The patient ultimately underwent below-the-knee amputation and subsequent revision to above-the-knee amputation.

Amputation, Surgical↗

Environmental investigation of a legionellosis outbreak in western Sydney: the role of molecular profiling.

This investigation used DNA profiling in an attempt to identify the environmental source of a community outbreak of 11 cases of Legionnaires' disease. Nine of these cases were culture positive and a single strain (DNA profile) of Legionella pneumophila serogroup 1 was isolated from eight cases. Spot water samples were collected from 51 cooling towers implicated by case exposure histories; this same strain was isolated from four towers at three separate locations up to 6 km apart. None of these locations had been frequently implicated by case histories. Because we did not perform an analytic epidemiological investigation, we were unable to identify a single environmental source for the outbreak. It is also possible that this outbreak was multifocal. The use of molecular profiling should not overshadow the importance of epidemiological methods in these environmental investigations. More data is needed regarding the prevalence, distribution, and clinical significance (virulence) of environmental L. pneumophila strains. This would aid interpretation of molecular profiling used in investigations of community legionellosis outbreaks.

Australia↗

Chordin regulates primitive streak development and the stability of induced neural cells, but is not sufficient for neural induction in the chick embryo.

We have investigated the role of Bone Morphogenetic Protein 4 (BMP-4) and a BMP antagonist, chordin, in primitive streak formation and neural induction in amniote embryos. We show that both BMP-4 and chordin are expressed before primitive streak formation, and that BMP-4 expression is downregulated as the streak starts to form. When BMP-4 is misexpressed in the posterior area pellucida, primitive streak formation is inhibited. Misexpression of BMP-4 also arrests further development of Hensen's node and axial structures. In contrast, misexpression of chordin in the anterior area pellucida generates an ectopic primitive streak that expresses mesoderm and organizer markers. We also provide evidence that chordin is not sufficient to induce neural tissue in the chick. Misexpression of chordin in regions outside the future neural plate does not induce the early neural markers L5, Sox-3 or Sox-2. Furthermore, neither BMP-4 nor BMP-7 interfere with neural induction when misexpressed in the presumptive neural plate before or after primitive streak formation. However, chordin can stabilise the expression of early neural markers in cells that have already received neural inducing signals. These results suggest that the regulation of BMP signalling by chordin plays a role in primitive streak formation and that chordin is not sufficient to induce neural tissue.

Amino Acid Sequence↗

The epidemiology of tuberculosis in New South Wales 1975-1995: the effects of immigration in a low prevalence population.

SETTING: New South Wales (NSW) is Australia's most populous state and is home to one third of the country's rapidly growing immigrant population. OBJECTIVE: To examine the effects of immigration upon the epidemiology of tuberculosis (TB) in a low prevalence population. DESIGN: A retrospective review of state TB surveillance data in NSW from 1975-1995. RESULTS: The crude notification rate for all active TB declined from 12.2 per 100000 population in 1975 to 5.2/100000 in 1986, after which the notification rate increased steadily to 7.6/100000 in 1995. Between 1975 and 1995, the proportion of all TB notifications occurring in overseas-born residents increased from 30% (178/601) to 79% (345/435). During this period, the proportion of new extra-pulmonary TB notifications increased from 13% (72/549) to 42% (171/405). Notifications amongst women increased from 31% (188/601) to 47% (218/462) of the total, while the median age at notification fell from 55 to 41 years. The pattern of TB disease has not changed for Australian-born cases, who are mostly elderly men with pulmonary disease. Multidrug-resistant TB remains uncommon (<1%), and co-infection with the human immunodeficiency virus (HIV) and TB has not emerged as a major problem (2% of notifications), but is poorly documented. CONCLUSION: TB has re-emerged in NSW predominantly because of increased immigration from high prevalence countries. The epidemiology of TB has become dominated by overseas-born notifications, and now younger adults are primarily affected. Enhancing the effectiveness of the TB screening procedures for immigrants is a priority. Information should be provided to all immigrants and to long-term visitors from countries of high TB prevalence regarding TB infection and the TB services available in Australia.

Adolescent↗

Effect of irradiation with a low-intensity diode laser on the metabolism of equine articular cartilage in vitro.

OBJECTIVE: To determine whether irradiation with a low-intensity diode laser, which produces radiation at a wavelength of 810 nm, will induce nonthermal enhancement of chondrocyte metabolism. SAMPLE POPULATION: 144 grossly normal articular cartilage explants aseptically harvested from the femoral condyles of 6 adult horses. PROCEDURE: Treated cartilage explants were irradiated with a diode laser at 1 of 7 fluence levels that ranged from 8 to 1,600 J/cm2. Explants were incubated for 24 or 72 hours, labeled for 24 hours with [35S]Na2SO4, and assayed for newly synthesized sulfated glycosaminoglycan (GAG; measured incorporation of 35SO4) and endogenous GAG, chondroitin 6-sulfate (CS), and keratan sulfate (KS) content, using a dimethylmethylene blue assay. Laser-induced temperature changes were measured during irradiation with a diode laser and a neodymium:yttrium aluminum garnet (Nd:YAG) laser, which produces radiation at a wavelength of 1,064 nm, using conditions that were reported in previous studies to increase explant metabolism. RESULTS: After incubation for 24 or 72 hours, rate of 33SO4 uptake or endogenous GAG, CS, or KS content in irradiated explants was not significantly different than in nonirradiated explants. Cartilage temperature increased < 4.75 C during diode laser application. Cartilage temperature increased 5 to 12 C during Nd:YAG laser application. CONCLUSIONS: Minimal thermal increases in cartilage explants with use of a low-intensity diode laser resulted in no change in proteoglycan metabolism of chondrocytes. An increase in tissue temperature over a narrow range with use of a Nd:YAG laser may have contributed to the metabolic alteration of chondrocytes reported in previous studies.

Animals↗

Unbalanced t(4;11)(q32;q23) in a 34-year-old man with manifestations of distal monosomy 11q and trisomy 4q syndromes.

We present a 34-year-old man with an unbalanced translocation between the long arms of chromosome 4 and chromosome 11. He had manifestations of monosomy 11(q23)--minor facial anomalies, abnormal head shape, cryptorchidism; trisomy 4(q32)--hirsutism, renal disease; and manifestations attributable to both imbalances--heart disease, musculoskeletal anomalies, and mental retardation. FISH studies showed that the chromosome 11q23.3 translocation breakpoint was distal to the rare folate sensitive fragile site (FRA11B). The patient is the oldest reported with both imbalance of 4q+ and 11q-.

Adult↗

Pertussis notifications in Australia, 1991 to 1997.

Although pertussis is a vaccine-preventable disease, it has been epidemic in Australia since 1993 and recently claimed the lives of four children under three months of age. We reviewed national notifications of pertussis from 1991 to 1997 and found notification rates ranged from 2.0 per 100,000 population in 1991 to a peak of 30.5 per 100,000 population in 1994 despite pertussis vaccination coverage approaching 90% for the three-dose primary course. We found that notification rates were highest in infants (< 1 year of age) and school aged children (5-14 years of age). Although there was a resurgence of pertussis in 1996, age-specific notification rates decreased for children aged 1-7 years and it appears that the diphtheria-tetanus-pertussis (DTP) booster introduced as a fifth dose at 4-5 years may be having an effect. We raise the possibility that the current whole cell pertussis vaccine may be providing only short-term immunity and that our results may reflect low or inadequate vaccine coverage among both the population at large and the individual cases. We identify gaps in the national surveillance system which require attention including under-reporting and the need for information on vaccination status of notified cases; method of diagnosis; and date of birth or age in months to identify the proportion of infants in the highest risk group, that is under six months of age.

Age Factors↗

Regioselective effect of zwitterionic DNA substitutions on DNA alkylation: evidence for a strong side chain orientational preference.

The incorporation of zwitterionic residues (5-substituted omega-aminoalkyl-2'-deoxypyrimidines) into DNA has been reported to bend DNA as measured by aberrant gel mobility [Strauss et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 9515-9520]. Herein we report that DNA methylation by N-methyl-N-nitrosourea at N7-guanine is regioselectively inhibited by point substitutions of the zwitterionic residues 5-(6-aminohexyl)-2'-deoxycytidine, 5-(6-aminohexyl)-2'-deoxyuridine, or 5-(3-aminopropyl)-2'-deoxyuridine. No inhibition is observed for DNA methylation by dimethyl sulfate. On the basis of inhibition patterns for methylation with the different zwitterionic substitutions and the different length tethers, the omega-aminoalkyl side chains prefer to adopt a conformation that points them toward the 3'-base. Molecular modeling grid searches, coupled with energy minimizations, and simulated annealing molecular dynamics studies indicate that unfavorable steric interactions with the 5'-base and backbone, as well as stabilizing electrostatic interactions with electronegative atoms on the 3'-side, are responsible for the observed conformational preference. No evidence for association of the cationic side chain with the phosphate backbone is observed. The observed bending of DNA induced by the tethered ammonium ions may simply arise from their localization in the major groove.

Circular Dichroism↗

The role of 5-HT(1B/1D) receptors in the modulation of 5-hydroxytryptamine levels in the frontal cortex of the conscious guinea pig.

The role of 5-HT(1B/1D) receptors in modulating extracellular 5-hydroxytryptamine (5-HT) levels in the guinea pig was investigated with the non-selective 5-HT(1B/1D) receptor inverse agonist, methiothepin, and the selective 5-HT(1B/1D) receptor partial agonists, GR 127935 (n-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]-4-carboxamide) and GR 125743 (n-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-3-methyl-4-(4-pyri dinyl)benzamide). Extracellular 5-HT levels were measured using the technique of brain microdialysis, in the frontal cortex of the freely moving guinea-pig. Extracellular 5-HT was tetrodotoxin sensitive and calcium dependent, and increased when perfused with a high concentration of K+. In addition, extracellular 5-HT levels were lowered by the 5-HT(1B/1D) receptor agonist, sumatriptan, and the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin, while perfusion of the selective serotonin re-uptake inhibitor, paroxetine, increased 5-HT in a concentration-dependent manner. Perfusion of methiothepin, GR 127935 and GR 125743 into the frontal cortex caused significant but transient increases of extracellular 5-HT. However, systemic administration of methiothepin, GR 127935 and GR 125743, at 0.3 mg/kg i.p., produced significant decreases in extracellular 5-HT, to minima of 27 +/- 3%, 31 +/- 12% and 27 +/- 13% of basal, respectively. The increase of extracellular 5-HT, following 5-HT(1B/1D) receptor inverse and partial agonist perfusion into the frontal cortex, was probably a consequence of attenuation of an endogenous 5-HT tone at terminal 5-HT autoreceptors. The unexpected decrease in 5-HT levels following systemic administration may be a result of additional attenuation of endogenous 5-HT tone at cell body autoreceptors in the raphe. Such an increase in local 5-HT levels could then stimulate 5-HT1A receptors to inhibit cell firing and hence decrease 5-HT levels in the terminal regions. This was confirmed when co-administration of the 5-HT1A receptor antagonist, WAY 100635, significantly attenuated the GR 127935 decrease in 5-HT.

Animals↗

Invasive Streptococcus pneumoniae in Perth teaching hospitals, 1990 to 1994.

Streptococcus pneumoniae causes pneumonia, otitis media and meningitis. Reports of penicillin resistance and the development of vaccines highlight the need for baseline information about pneumococcal disease in Australia. We surveyed Perth teaching hospital laboratory records for the period 1990 to 1994 for isolates of S. pneumoniae recovered from normally sterile sites, and obtained isolate and patient demographic information. Highest rates of invasive disease were found at the extremes of age and were associated with Aboriginality. Isolates were rarely penicillin resistant. Surveillance of invasive pneumococcal disease will be of importance in monitoring the emergence of penicillin resistance and the impact of conjugate vaccines.

Adolescent↗

Comparison of out of hours care provided by patients' own general practitioners and commercial deputising services: a randomised controlled trial. I: The process of care.

OBJECTIVE: To compare the process of out of hours care provided by general practitioners from patients' own practices and by commercial deputising services. DESIGN: Randomised controlled trial. SETTING: Four urban areas in Manchester, Salford, Stockport, and Leicester. SUBJECTS: 2152 patients who requested out of hours care, and 49 practice doctors and 183 deputising doctors (61% local principals) who responded to those requests. MAIN OUTCOME MEASURES: Response to call, time to visit, prescribing, and hospital admissions. RESULTS: 1046 calls were dealt with by practice doctors and 1106 by deputising doctors. Practice doctors were more likely to give telephone advice (20.2% v 0.72% of calls) and to visit more quickly than deputising doctors (median delay 35 minutes v 52 minutes). Practice doctors were less likely than deputising doctors to issue a prescription (56.1% v 63.2% of patients) or to prescribe an antibiotic (43.7% v 61.3% of prescriptions issued) and more likely to prescribe genetic drugs (58.4% v 32.1% of drugs prescribed), cheaper drugs (mean cost per prescription pounds 3.28 v pounds 5.04), and drugs in a predefined out of hours formulary (49.8% v 41.1% of drugs prescribed). There was no significant difference in the number of hospital admissions. CONCLUSIONS: By contrast with practice doctors, deputising doctors providing out of hours care less readily give telephone advice, take longer to visit at home, and have patterns of prescribing that may be less discriminating.

Appointments and Schedules↗