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Biomedical subjects

S Harris

Publications and source records attributed to S Harris.

At least 127 records · Page 7Linked to original sources
PubMed1996

Myotonic dystrophy: will the real gene please step forward!

The mutation underlying myotonic dystrophy (DM) was identified at the end of 1991 amidst great rejoicing from the patients supporting the research and, not least, from those who spent so long searching for it. Subsequently, the molecular genetic phenomena associated with DM have been clearly explained by the transmission behaviour of the expanding repeat, which remains the only mutation that has been described in patients. We understand the molecular basis of anticipation, why the severe congenital form is almost exclusively transmitted by affected mothers and we have widely accepted models of the population genetics of DM. Yet, despite all these clearly explained molecular events, we appear to be hardly any closer to understanding the molecular pathology of DM than when the mutation was first identified. To understand the reason for this, we have to look in detail at the mutation itself, and in particular at the locus and its complex nuances. In doing so, we begin to realise that DM is unique amongst the Mendelianly inherited disorders, in that the mutation, because of its location in a very gene-rich region of the genome, probably simultaneously renders several genes dysfunctional. The somatic heterogeneity of the repeat, coupled with the involvement of several genes, accounts for the pleiotropy observed in the phenotype. Added to this complexity is the uncertainty of the level at which gene dysfunction or gain of function is occurring. It is possibly at the level of DNA/chromatin structure and/or RNA regulation/processing, and all of these pathways may, in different tissues, contribute to the final phenotype.

Animals↗
PubMed1996

Randomized controlled trial of cervical cap with intracervical reservoir versus standard intracervical injection to inseminate cryopreserved donor semen.

A prospective controlled study of donor insemination without sperm preparation or ovarian stimulation was performed to compare the use of a cervical cap incorporating an intracervical reservoir with a standard intracervical injection technique to inseminate 0.5 ml cryopreserved semen. Treatments were alternated in successive cycles in each patient after initial randomized selection. A total of 198 patients had 635 treatment cycles (median 3, range 1-7), 309 with reservoir and 326 by standard injection. A total of 56 women became pregnant, 24 (7.8% per cycle) with the reservoir and 32 (9.8% per cycle) by injection. There were no significant differences between the pregnancy rates per cycle overall or cycle-specific cumulative rates calculated using the life-table method. There were no significant differences in age, parity, baseline gonadotrophin measurements, mid-luteal serum progesterone concentrations, frequency of adverse fertility factors in the woman or her partner's cause of infertility between women who conceived and those who failed to conceive. We conclude that use of a cervical reservoir and cap for donor insemination does not offer any advantage over standard intracervical insemination.

Adult↗
PubMed1996

Hemostasis at skin graft donor sites: evaluation of topical agents.

Blood loss from split-thickness skin graft donor sites may be significant. Various topical agents have been used to decrease this blood loss, including thrombin and epinephrine solutions of varying concentrations. We describe a K-Y jelly/epinephrine mixture that serves both as a lubricant for the dermatome and as a hemostatic agent. This mixture, in comparison with other topical agents, produces rapid hemostasis and offers the advantages of easy use, ready availability, and low cost. The blood loss savings based on this hemostatic technique is quantifiable and significant.

Administration, Topical↗
PubMed1996

Transdermal fentanyl administration in children and adolescents with sickle cell pain crisis.

PURPOSE: The purpose of this study was to determine the dose-concentration relationship and clinical effect of transdermal fentanyl (TF) in patients with sickle cell pain crisis (SCPC). PATIENTS AND METHODS: Ten patients aged 9-16 years were studied. Patients initially received a TF dose of 25 (n = 7) or 50 (n = 3) micrograms/h if morphine use was > 2.5 mg/h. Supplemental morphine usage via patient-controlled analgesia (PCA), sedation status, pain status, respiratory rate, pulse rate, oxygen saturation, and blood pressure were monitored. RESULTS: The average TF dose was 0.77 +/- 0.37 micrograms/kg/h on day 1 and 1.17 +/- 0.46 micrograms/kg/h on day 2. Fentanyl concentrations measured at 24 and 48 h were 0.60 +/- 0.31 and 1.18 +/- 0.44 ng/ml, respectively. A significant relationship existed between TF dose and fentanyl concentration (r2 = 0.56, p < 0.01). There was no difference in any of the clinical monitoring parameters between day 1 and day 2. However, 7 of 10 patients reported subjective improvement in pain control over that achieved with PCA alone. No adverse effects were noted. CONCLUSIONS: Improved understanding of the dose-effect relationship for TF in children and adolescents is necessary before adequate pain control can be achieved with this delivery system.

Administration, Cutaneous↗
PubMed1996

Bicistronic vector for the creation of stable mammalian cell lines that predisposes all antibiotic-resistant cells to express recombinant protein.

We have developed an improved vector for the stable expression of recombinant protein in mammalian cells. In this vector, designated pCIN, both the recombinant cDNA and the neomycin phosphotransferase selection marker are transcribed from a single promoter element. To facilitate translation of the second open reading frame, the encephalomyocarditis virus internal ribosome entry site has been inserted into the expression cassette immediately before the start codon of this sequence. We report the use of this vector to generate stable cell lines expressing the human 5-HT1Da serotonin receptor and show that following transfection and clonal selection, all ten cell lines characterized express similar and high levels of receptor (1.5-11.9 pmol receptor/mg protein). Use of pCIN should permit the rapid and efficient production of stable mammalian cell lines for the characterization of recombinant protein, as this vector appears to predispose all transfected cells to express such protein.

Animals↗
PubMed1996

The union movement: legislative and regulatory issues in California.

In the late 1980s, hospitals began to identify that patient care services needed to be restructured to deliver services in a more cost-effective and efficient way. As more and more hospitals adopted this philosophy, unions began to take an increasingly aggressive role advocating against the strategies that hospitals employed, which often put unlicensed assistive personnel in a role that more appropriately used the professional training of a registered nurse. The strategies taken by the unions took several forms: regulatory and legislative, which sought to preserve nurses' jobs through mandatory staffing ratios; a public relations campaign aimed at discrediting hospitals that have restructured and informing the public that the changes jeopardize patient welfare; and targeted organizing. This article addresses the impact the union strategies have had on hospitals and the changing health care market.

California↗
PubMed1996

Joint attention and language gains in children with Down syndrome.

Joint attention and topic initiation in caregiver-child interactions was explored in relation to children's language gains over 13 months. Caregivers of 28 children with Down syndrome spent more time in joint attention and maintained more attention to caregiver-selected toys than did caregivers of 17 children with typical development. Receptive language gains of children with Down syndrome were associated with caregivers maintaining attention to child-selected toys and with longer lengths of joint attention. Caregivers redirecting attention away from child-selected toys and a greater frequency of joint attention episodes was negatively associated with children's language gains. More time spent in joint attention and caregivers maintaining attention to mother-selected toys was associated with receptive language gains in children who were developing typically.

Attention↗
PubMed1996

Familial deletion of chromosome 18 (p11.2).

Familial transmission of del (18p) syndrome from a mother to her daughter is rare and has been reported only once before. We report a female patient referred to us at age 18 years because of mental retardation associated with short stature. Similar clinical features are also seen in her mother. Chromosome analysis revealed a 46,XX, del (18) (p11.2) karyotype in both the proposita and her mother. Fluorescence in situ hybridization with whole chromosome paint for chromosome 18 showed no evidence of translocation. Because of the familial transmission of del (18p), this case has wider implications in genetic counseling.

Adolescent↗
PubMed1995

Bovine tuberculosis in badger (Meles meles) populations in southwest England: the use of a spatial stochastic simulation model to understand the dynamics of the disease.

A spatial stochastic simulation model was developed to describe the dynamics of bovine tuberculosis in badger populations in southwest England, based on data from the literature and from unpublished sources. As there are no data on intra- and intergroup infection probabilities, estimates of these were obtained through repeated simulations based on field observations of the spread and prevalence of the disease. The model works on a grid-cell basis, with each grid cell potentially occupied by one badger social group; immigration to and emigration from the main grid are incorporated. Population regulation is assumed to occur at the group level through density-dependent fecundity and cub mortality, and the model can be run for various disease-free equilibrium group sizes (which are determined by the carrying capacity of the environment). The model works on a quarterly (three-monthly) basis and processes are stochastic at the individual level. Three classes of individual (adults, yearlings and cubs) and three classes of infection (susceptible, infected-but-not-infectious and infectious) are recognized. Bovine tuberculosis wa shown to persist in badger populations for long periods of time, even in populations with a disease-free equilibrium group size of only four adults and yearlings. However, with standard rates of intergroup infection and movement, the disease only became endemic in populations with a disease-free equilibrium group size greater than six adults and yearlings. In the endemic situation, the prevalence of the disease ranged between 11-22 degrees depending on the combination of inter- and intragroup infection probabilities used. Endemic infection within the homogeneous environment of the grid was characterized by a high degree of heterogeneity. Patches of infection were spatio-temporally unstable, but shifted in location relatively slowly. Spread of the disease from a point source of infection with standard rates of intergroup movement and infection only occurred to any marked extent in populations with disease-free equilibrium group sizes of eight or more adults and yearlings. Increasing the intergroup infection probability had a significant effect on increasing the probability and rate of spread, and considerably lowered the threshold group size for spread from a point source to around four adults and yearlings. However, increasing the rates of intergroup movement reduced the probability of spread of the disease except at the largest groups sizes. When both intergroup infection and movements were increased, the effects of increased infection in enhancing spread were offset to some degree by the increased movements. Perturbation to the badger population, as may be caused by control operations, could therefore increase the probability of persistence or spread of an infection.

Animals↗
PubMed1995

Bovine tuberculosis in badger (Meles meles) populations in southwest England: an assessment of past, present and possible future control strategies using simulation modelling.

A spatial stochastic simulation model was used to compare the efficacy of different badger control policies and to determine the theoretical requirements for the control of endemic bovine tuberculosis in badger populations in southwest England. Culling-based strategies for controlling endemic disease were compared with strategies employing a yet-to-be-developed oral vaccine which would provide uninfected badgers with immunity to the infection. A comparative assessment was made of the efficacy of previous and proposed culling-based strategies employed by the Ministry of Agriculture, Fisheries and Food for the control of localized disease, and the potential for an oral vaccine-based strategy for the control of localized disease was examined. For endemic bovine tuberculosis, to achieve a reasonable probability (p > 0.70) of successful control with a strategy involving a single culling operation, a very high proportion of the badger population (> 90%) must be culled. Single vaccination would not be successful in combating endemic disease. However, strategies involving repeated annual vaccination would have a very high probability of eradicating endemic disease, even with a relatively low (40-50%) annual vaccination efficiency. The most successful culling-based strategies for the control of localized disease were the gassing and clean ring strategies. Compared with no control at all, the interim strategy only offered benefits of a lower probability of disease spread and persistence in populations with low disease-free equilibrium group sizes or low initial prevalences of infection. In all other instances the benefits were negligible. The live test strategy will offer an improvement over the interim strategy, but will not be as effective as either the gassing or clean-ring strategies. In addition, it is likely to necessitate the culling of approximately four times as many badgers each year as the interim strategy, and the proportion of those killed that are infected will be approximately half that under the interim strategy. The efficacy of a strategy involving annually repeated oral vaccination of the badgers within a similar area to that covered by the live test depended on the efficiency of vaccination. A vaccination efficiency of 20-60% represented an overall improvement in efficacy over the interim strategy, being equivalent to the live test strategy. However, only vaccination efficiencies of 60-80% or greater achieved similar results to the gassing strategy, and none were so successful as the clean-ring strategy. Recommendations for future management are provided. Reactive strategies based on culling or vaccination will not solve the problem of bovine tuberculosis in badgers. Proactive strategies directed in those areas with a recent history of bovine tuberculosis in badgers should be considered as an alternative short-term control measure. The only strategy likely to eradicate bovine tuberculosis from badger populations in the long term is the use of repeated vaccination in proactive control operations in areas with a history of bovine tuberculosis in the badger population. Analyses should be conducted to evaluate whether the economic benefits of the live-test strategy are likely to outweigh its economic and ecological costs and whether continued research into the development of a vaccine for badgers is likely to offer any significant long-term economic benefits.

Animals↗
PubMed1995

Azithromycin and terfenadine: lack of drug interaction.

A double-blind placebo-controlled study was conducted in healthy men to determine the effect of coadministration of azithromycin on the pharmacodynamics and pharmacokinetics of terfenadine. Administration of 500 mg azithromycin for 1 day and 250 mg on 4 subsequent days did not affect the pharmacokinetics of the pharmacologically active terfenadine carboxylate metabolite when 60 mg terfenadine was given twice daily for 12 days, starting 7 days before azithromycin administration. Terfenadine alone resulted in a 0.010 msec increase in the rate-corrected QT interval (QTc), but the incremental effects of azithromycin and placebo on QTc in volunteers receiving terfenadine were not statistically different. It is concluded that the potentially life-threatening disorders that have been attributed to a pharmacokinetic interaction between macrolide antibiotics and terfenadine are unlikely to take place in patients treated simultaneously with azithromycin and terfenadine.

Adult↗
PubMed1995

Exercise versus overnight albumin excretion rates in subjects with type 1 diabetes.

Diabetic nephropathy is the leading cause of new cases of renal failure in the US and Europe. An elevated albumin excretion rate (AER) on an overnight urine sample is considered an early predictor of end-stage renal failure. An elevated AER on a post-exercise urine sample has previously been considered to be an even earlier marker of renal damage. In a longitudinal prospective study, 373 subjects with insulin-dependent (type 1) diabetes mellitus had a total of 714 renal evaluations, each of which included one exercise and two overnight urine collections for AER determinations. All subjects were at least 13 years old and had diabetes for at least 4 years. There was a strong correlation between exercise and overnight AERs (r = 0.74, P < 0.001). For the 60 subjects with an initial borderline increase of either overnight or exercise AER, the overnight AER values (7.6-20 micrograms/min) progressed first for 52% of subjects whereas the exercise AERs (41-114 micrograms/min) progressed first for 43% of subjects (5% had simultaneous elevations of both). For the 22 subjects in which an abnormal overnight (> 20 micrograms/min) or exercise (> 114 micrograms/min) value was detected first, 17 (77%) had an elevated exercise AER first, whereas only 4 (18%) had an elevated overnight AER first. This study shows that an increase of either the exercise or the overnight AER can occur first, dependent upon the level of abnormality being considered. The two tests correlate closely with one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗