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Biomedical subjects

J Keenan

Publications and source records attributed to J Keenan.

At least 19 recordsLinked to original sources
PubMed2004

A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin.

Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasion through matrigel and membrane pores, by decreased adhesion to extracellular matrix proteins and by increased motility. This may represent an in vitro model of a step in the metastatic process occurring subsequent to invasion. The paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubicin-selected variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr-10p10p, in contrast, exhibited only small increases in resistance to doxorubicin, although they were slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to paclitaxel, carboplatin and 5-fluorouracil.

Adult↗
PubMed2003

Patient demographics as a predictor of the ten-year survival rate in primary total knee replacement.

s the surgical indications for total knee replacement (TKR) expand to include younger, heavier and more active patients, knowledge of the effect of these demographic variables on the outcome and survival of the implant is increasingly important. Between November 1986 and September 1990, 402 patients underwent 562 primary cemented cruciate-retaining TKRs carried out by a single surgical team. The overall results showed a survival of 96.8% at 14 years with 1.44% lost to follow-up. Evaluating the demographics of these patients showed that certain groups fared significantly less well. The best results were seen in non-obese women with osteoarthritis who were over 60 years of age in whom there was ten-year survival of 99.4%. The worst results were in obese men with osteoarthritis who were less than 60 years of age in whom there was a ten-year survival of 35.7%. Caution should be exercised when considering TKR on a patient with this combination of poor risk factors. By identifying demographic factors at the time of consultation the surgeon is better able to predict the survival of the TKR. This information is important when considering the best options for treatment of a patient and in providing accurate information during preoperative counselling.

Adult↗
PubMed2003

Correlation of age, acromial morphology, and rotator cuff tear pathology diagnosed by ultrasound in asymptomatic patients.

The importance of acromial morphology in the pathogenesis of rotator cuff tears remains controversial. Some surgeons place great emphasis on acromial morphology and others feel that acromial shape is a result of cuff tear pathology rather than the cause. The purpose of this study was to determine if there was an association between acromial morphology, age, and rotator cuff tears found by ultrasound in asymptomatic volunteer subjects with no past history of shoulder symptoms. One hundred eighteen outlet x-rays and ultrasound scans were performed in 59 asymptomatic patients in various age groups. Acromial morphology and the age of the patients were then correlated with the ultrasound findings. Older patients were noted to have a high incidence of type II and type III acromions (93% of those over 70). Full- and partial-thickness tears were more commonly seen in patients with type II or type III acromions compared with type I. Patients over 50 years had a high incidence of full-thickness tears (40%), but the incidence did not increase with increasing age past 50. These findings lend credence to the multifactorial etiology of rotator cuff tears. The patient's age (degeneration) and acromial morphology (impingement) are two of the factors involved in causing rotator cuff tears. The incidence of cuff tears and type III acromions was high in this group of entirely asymptomatic volunteer subjects. Surgeons should interpret radiologically hooked or curved acromions as well as rotator cuff tears diagnosed with ultrasound or other modalities with caution. It may well be that both of these findings should be regarded as part of the natural ageing process.

Acromion↗
PubMed2001

Albuterol delivery in a neonatal ventilated lung model: Nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers.

The aim of this study was to compare albuterol delivery in a neonatal ventilated lung model, using three delivery methods: 1) jet nebulizer; 2) chlorofluorocarbon-pressurized metered dose inhaler (CFC-MDI) actuated into an ACE(R) spacer; and 3) hydrofluoroalkane-pressurized MDI (HFA-MDI) actuated into an ACE(R) spacer. The bench model consisted of a mechanically ventilated infant test lung with ventilator settings to simulate a very low birth weight neonate with moderate lung disease. Albuterol solution (0.5%) was nebulized at the humidifier and temperature port, 125 cm and 30 cm from the Y-piece, respectively. Albuterol metered dose inhalers (MDIs) were actuated into an ACE(R) spacer that was tested in two positions: 1) inline between the endotracheal (ET) tube and the Y-piece; and 2) attached to the ET tube and administered by manual ventilation. Albuterol was collected on a filter at the distal end of the ET tube and was quantitatively analyzed by high performance liquid chromatography. Albuterol delivery by CFC-MDI (position 1, 4.8 +/- 1.0%, vs. position 2, 3.8 +/- 1.6%, P > 0.05) and HFA-MDI (position 1, 5.7 +/- 1.6%, vs. position 2, 5.5 +/- 2.4%, P > 0.05) were significantly greater than delivery by nebulization at 30 cm (0.16 +/- 0.07%) and 125 cm (0.15 +/- 0.03%) from the Y-piece (P < 0.001). A single actuation of albuterol MDI delivered the equivalent of nebulizing 2.5-3.7 mg of albuterol solution. We conclude that albuterol administered by MDI and ACE(R) spacer resulted in more efficient delivery than by nebulization in this mechanically ventilated neonatal lung model. There was no significant difference in drug delivery between CFC-MDI and HFA-MDI; nor did the placement of the spacer significantly affect drug delivery.

Administration, Inhalation↗
PubMed2000

Treatment of supracondylar femoral fracture above total knee replacement by custom made hinged prosthesis.

A supracondylar fracture above a total knee arthroplasty (TKA) is a devastating complication for both the patient and surgeon. Various methods of treatment are available. We have treated seven cases of displaced supracondylar fractures above a total knee replacement with custom made implants. This technique allows rapid post-operative recovery and gives a good functional outcome.

Journal Article↗
PubMed2000

A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori infection.

Helicobacter pylori infection in humans is associated with diverse of clinical outcomes which are partly attributed to bacterial strain differences. Secreted bacterial products are thought to be involved in the pathogenesis caused by this non-invasive bacterium. Electron microscopy of gastric biopsies from infected individuals revealed blebbing of the H. pylori outer membrane, similar to the process of outer membrane vesicle shedding which occurs when the bacterium is grown in broth. Porins, a class of proinflammatory proteins, were observed in the outer membrane vesicles. The VacA cytotoxin, which is produced by 50-60% of H. pylori strains and associated with increased pathogenesis of infection, was also found to be vesicle-associated and biologically active. This supports the hypothesis that these vesicles represent a vehicle for the delivery of damaging bacterial products to the gastric mucosa.

Bacterial Outer Membrane Proteins↗
PubMed2000

Accumulation of CO(2) in reservoir devices during simulated neonatal mechanical ventilation.

Aerosolized albuterol is frequently administered to mechanically ventilated neonates by metered dose inhaler (MDI) and a reservoir device. These reservoirs are often placed between the Y-piece and endotracheal tube, thereby creating mechanical dead space and increasing the risk of rebreathing carbon dioxide (CO(2)). The objectives of this study were: 1) to quantify CO(2) accumulation in two commonly used reservoirs (ACE(R), Aerochamber(R)-MV) and a bidirectional nonreservoir actuator (Airlife(R) Minispacer) during mechanical ventilation of a neonatal lung model; and 2) to determine the effect of tidal volume (V(T)) on CO(2) accumulation. We hypothesized that the accumulation of CO(2) in these devices is clinically insignificant at the small tidal volumes used in mechanically ventilated premature neonates. The model was constructed to simulate CO(2) exhalation by a ventilated neonate and consisted of a neonatal ventilator circuit (rate = 40/min; peak inspiratory pressure (PIP) = 20 cm H(2)0) attached to a reservoir/actuator and neonatal test lung. The ventilator delivered inspiratory gas (room air) to the test lung, which was vented into the atmosphere by a small adjustable leak. Expiration was simulated by manually ventilating 7.1% CO(2) (partial pressure of CO(2) (PCO(2)) = 48 mm Hg) back through the model. Accumulation of CO(2) within the reservoir/actuator was measured using an end-tidal CO(2) monitor. Each 4-min experiment was conducted at three V(T) (7.5 mL, 15 mL, and 25 mL), and the median PCO(2) was calculated in 0.5-min increments. For V(T) = 7.5 mL, CO(2) accumulated slowly in the ACE(R) and Minispacer(R) and reached a maximum at 4.0 min (PCO(2) = 2.3 mm Hg and 7.3 mm Hg, respectively). In contrast, the Aerochamber(R)-MV rapidly reached a PCO(2) of 9.5-10.0 mm Hg by 1-1. 5 min. A similar trend occurred with V(T) = 15 mL; however, higher partial pressures (approximately 10-12 mm Hg) were achieved with all devices. At V(T) = 25 mL, PCO(2) rose rapidly with the ACE(R), Aerochamber(R)-MV, and Minispacer(R), reaching peaks of 17.2, 12.3, and 20.3 mm Hg, respectively (P < 0.05). In conclusion, accumulation of CO(2) in reservoir/actuator depends on V(T) as well as the chamber design and internal volume. Due to the short duration of use when administering drugs via MDI, accumulation of CO(2) in these devices is not likely to be clinically relevant for the majority of ventilated newborns.

Carbon Dioxide↗
PubMed2000

Immune response to an 18-kilodalton outer membrane antigen identifies lipoprotein 20 as a Helicobacter pylori vaccine candidate.

Experiments were performed using the standardized murine model of Helicobacter pylori infection to determine the immunogenicity of H. pylori outer membrane vesicles in immune protection. These vesicles, which are naturally shed from the surface of the bacterium, induce a protective response when administered intragastrically to mice in the presence of cholera holotoxin, despite the absence of the urease enzyme and associated Hsp54 chaperonin. Immunoblotting identified a specific serum immunoglobulin G (IgG) response to an 18-kDa outer membrane protein in a significant number of immunized animals. This commonly expressed, immunodominant protein was subsequently identified as lipoprotein 20 (Lpp20). Hybridoma backpacks secreting an IgG1 subclass monoclonal antibody to Lpp20 were generated in H. pylori-infected mice and were found to significantly reduce bacterial numbers, providing evidence that this surface-exposed antigen is a true vaccine candidate and not merely an antigenic marker for successful, protective immunization.

Animals↗
PubMed2000

Preexercise carbohydrate ingestion, glucose kinetics, and muscle glycogen use: effect of the glycemic index.

Eight trained men cycled at 70% peak oxygen uptake for 120 min followed by a 30-min performance cycle after ingesting either a high-glycemic index (HGI), low-glycemic index (LGI), or placebo (Con) meal 30 min before exercise. Ingestion of HGI resulted in an elevated (P<0.01) blood glucose concentration compared with LGI and Con. At the onset of exercise, blood glucose fell (P<0.05) such that it was lower (P<0.05) in HGI compared with LGI and Con at 15 and 30 min during exercise. Plasma insulin concentration was higher (P<0.01) throughout the rest period after ingestion of HGI compared with LGI and Con. Plasma free fatty acid concentrations were lower (P<0.05) throughout exercise in HGI compared with LGI and Con. The rates of [6,6-(2)H]glucose appearance and disappearance were higher (P<0.05) at rest after ingestion and throughout exercise in HGI compared with LGI and Con. Carbohydrate oxidation was higher (P<0.05) throughout exercise, whereas glycogen use tended (P = 0.07) to be higher in HGI compared with LGI and Con. No differences were observed in work output during the performance cycle when comparing the three trials. These results demonstrate that preexercise carbohydrate feeding with a HGI, but not a LGI, meal augments carbohydrate utilization during exercise but does not effect exercise performance.

Adult↗
PubMed2000

McIndoe's scissors--a simple technique to aid distal locking of an intramedullary nail.

Distal locking of intramedullary nails may be difficult and time consuming. We describe a simple technique using a readily available instrument (McIndoe's scissors) to aid start of this procedure and to locate both distal locking holes at one time. By holding the scissors out of the operative field and facilitating rapid incisions, the operative procedure time and, importantly, the radiation exposure time may be reduced.

Bone Nails↗
PubMed1999

Transcranial magnetic stimulation and neuroplasticity.

We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.

Electromagnetic Phenomena↗
PubMed1999

A radiation hybrid map of the zebrafish genome.

Recent large-scale mutagenesis screens have made the zebrafish the first vertebrate organism to allow a forward genetic approach to the discovery of developmental control genes. Mutations can be cloned positionally, or placed on a simple sequence length polymorphism (SSLP) map to match them with mapped candidate genes and expressed sequence tags (ESTs). To facilitate the mapping of candidate genes and to increase the density of markers available for positional cloning, we have created a radiation hybrid (RH) map of the zebrafish genome. This technique is based on somatic cell hybrid lines produced by fusion of lethally irradiated cells of the species of interest with a rodent cell line. Random fragments of the donor chromosomes are integrated into recipient chromosomes or retained as separate minichromosomes. The radiation-induced breakpoints can be used for mapping in a manner analogous to genetic mapping, but at higher resolution and without a need for polymorphism. Genome-wide maps exist for the human, based on three RH panels of different resolutions, as well as for the dog, rat and mouse. For our map of the zebrafish genome, we used an existing RH panel and 1,451 sequence tagged site (STS) markers, including SSLPs, cloned candidate genes and ESTs. Of these, 1,275 (87.9%) have significant linkage to at least one other marker. The fraction of ESTs with significant linkage, which can be used as an estimate of map coverage, is 81.9%. We found the average marker retention frequency to be 18.4%. One cR3000 is equivalent to 61 kb, resulting in a potential resolution of approximately 350 kb.

Animals↗
PubMed1999

A comparison of lanreotide and octreotide LAR for treatment of acromegaly.

BACKGROUND AND OBJECTIVE: Two long-acting depot somatostatin analogues have recently been licensed for the treatment of acromegaly. We wished to assess the effectiveness of both these drugs in suppressing mean GH to a target of < 5 mU/l in patients with acromegaly unselected for responsiveness to octreotide, and also to compare the effects of both drugs METHODS: We prospectively studied 10 unselected patients with acromegaly who were treated first with lanreotide (LAN) and then octreotide LAR (LAR) following a washout period. The target for therapy was to achieve mean GH less than 5 mU/l. RESULTS: Five (50%) patients achieved mean GH < 5 mU/l on lanreotide 30 mg every 10 days, and 7 out of 9 (77.8%) achieved this level when the dose frequency was increased to every 7 days. On 20 mg octreotide LAR, 6 (60%) patients achieved the target mean GH and a further 2 (80%) when the dose was increased to 30 mg. Normalization of IGF-1 occurred in 5/9 (55.6%) patients who received lanreotide and 7/10 (70%) of those who received octreotide LAR. There was a significant difference in mean GH attained on the 2 drugs. The patients' mean GH was significantly lower when treated with octreotide LAR 20 mg every 4 weeks compared with lanreotide 30 mg every 10 days (P = 0.037). Maximal suppression of mean GH with 30 mg octreotide LAR or 7 day dosing of lanreotide was significantly greater on octreotide LAR (P < 0.02). CONCLUSIONS: At current dose recommendations, lanreotide and octreotide LAR are both effective in lowering mean GH to 'safe' (< 5 mU/l) levels in 80% patients but octreotide LAR treatment leads to significantly lower mean GH.

Acromegaly↗
PubMed1999

A concept analysis of autonomy.

Clinical and policy developments in health care have recently created demand for a professional response in terms of the development of advanced roles for nurses, notably 'nurse practitioner' roles. Such roles demand the exercise of autonomy, a term which eludes succinct definition despite the fact that the preparation of practitioners for these roles relies on a clear understanding of its nature. Utilizing an approach described by Wilson, this paper undertakes a concept analysis of autonomy, each step illustrated with examples taken from clinical practice, with the ultimate aim of offering an operational definition of autonomy.

Freedom↗