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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 37 records · Page 2Linked to original sources

Early intervention in psychosis: who wins, who loses, who pays the price?

The following article discusses Early Intervention in Psychosis services. It is contextualized with the rapidly changing psychiatric system. There is exploration of the reasons for a focus upon Early Intervention in Psychosis at this current time. The article then proceeds to discuss what may be needed for services to meet government targets. It concludes with some tentative answers and further questions to issues raised within the discussion.

Humans↗

Natural marine sponge fiber skeleton: a biomimetic scaffold for human osteoprogenitor cell attachment, growth, and differentiation.

Identification of suitable scaffolds onto which human stem cells can be seeded to generate functional three-dimensional tissues is a major research goal. A natural marine sponge skeleton was selected as a potential scaffold on the basis of the hydration potential of the fiber, the presence of open interconnected channels created by the fiber network, the collagenous composition of the fiber, and the structural diversity of fiber architecture. The skeleton of an undetermined species of Spongia (Class Demospongiae: Order Dictyoceratida: Family Spongiidae), composed of spongin, supported growth of human osteoprogenitor cells. Cell attachment and invasion into the framework were observed within 16 h, followed by development into membranous sheets between the sponge fibers by concentric infilling. Histochemical staining for alkaline phosphatase and type I collagen indicated formation of bone matrix as confirmed by birefringence. At 9 and 14 days alkaline phosphatase-specific activity in sponge fiber-osteoprogenitor cell cultures was significantly greater than in control cultures on cell culture plastic. Adsorption with recombinant human bone morphogenetic protein 2 confirmed the potential of this sponge skeleton as a delivery scaffold for osteogenic factors. The abundance and structural diversity of natural marine sponge skeletons and their potential as multifunctional, cell conductive and inductive frameworks indicate a promising new source of scaffold for tissue regeneration.

Animals↗

Isolation of an antifreeze peptide from the Antarctic sponge Homaxinella balfourensis.

Polar plants and animals survive in subzero waters (-2 degrees C) and many of these marine organisms produce antifreeze proteins (AFPs) to better adapt themselves to these conditions. AFPs prevent the growth of ice crystals which disrupt cellular membranes and destroy cells by inhibiting crystallization of water within the organism. The hydrophilic extract of an Antarctic sponge Homaxinella balfourensis exhibited a non-colligative freezing point depression effect on the crystal morphology of water. The extract was purified by repeated reverse phase high-pressure liquid chromatography, then assayed and shown to contain several AFPs. The major peptide was isolated, analyzed using matrix-assisted laser desorption ionization mass spectrometry and the partial structure of the peptide identified through amino acid sequencing. AFPs have potential applications in agriculture, medicine and the food industry.

Animals↗

Arthroscopic ACL reconstruction: a 5-9 year follow-up.

Arthroscopic ACL reconstruction has a satisfactory functional outcome of up to 90%, but there are few long-term prospective studies. This prospective study presents the outcomes of ACL reconstruction in terms of laxity, function and degenerative change, after a mean follow-up of 7 years. Function was assessed using the Lysholm and Tegner Activity Scores, laxity using the Stryker Knee Laxity Tester, employing maximum manual effort, and degenerative change was assessed as joint line narrowing on standardised radiographs. At latest follow-up, the mean Lysholm score improved from 70 to 87 and the Tegner from 4 to 7 (P<0.001). AP translation also improved (P<0.001). The incidence of early degenerative change was 50% and although this appeared to be associated with a previous meniscectomy, the correlation was not significant (P=0.06). In conclusion, the improved functional scores and laxity are sustained beyond 7 years but the 50% incidence of early degenerative change may be a cause for concern.

Anterior Cruciate Ligament↗

Mycobacterium triplex pulmonary infection in an immunocompetent patient.

We present the case of a 47-year-old immunocompetent patient with clinical evidence of pulmonary mycobacterial disease which was found to be due to Mycobacterium triplex. This novel organism is an uncommon, emerging, pathogen for which few reports of clinical infection exist in the medical literature.

Bronchoalveolar Lavage Fluid↗

Storage of blood for in vitro generation of dendritic cells.

BACKGROUND: Since the development of techniques to cultivate DC from peripheral blood, there has been a great deal of interest in the use of these cells in immunotherapeutic strategies. In a clinical setting, delays often occur between when blood is drawn and when it is processed. We therefore investigated the effect of overnight storage on the yield, morphology and phenotype of DC cultured from the peripheral blood of healthy volunteers. METHOD: Blood was processed either immediately, or after storage for 24 h in the fridge (4 degrees C) or at room temperature (RT, 20 degrees C). Samples were compared for starting cell number, DC yield and characteristics (morphology and phenotype). RESULTS: The number of PBMC that could be obtained was significantly lower from the refrigerated samples compared with both the freshly processed sample and that stored at RT. Samples processed after overnight storage at RT yielded cells morphologically identical to DC cultured from freshly processed samples. Only when samples were both stored and processed cold did the cultured cells not have typical DC morphology. DC cultured from the refrigerated samples showed a significant reduction in MHC II expression compared with samples processed fresh or stored at RT. This expression increased slightly when the sample was first warmed. Total DC yield and the percentage yield of cultured DC was not significantly different for any of the groups. DISCUSSION: We conclude that, if immediate processing of blood for in vitro generation of DC is not possible, samples should be stored at room temperature (approximately 20 degrees C).

Adult↗

A model for evaluating radiological impacts on organisms other than man for use in post-closure assessments of geological repositories for radioactive wastes.

Bioaccumulation and dosimetric models have been developed that allow the computation of dose rates to a wide variety of plants and animals in the context of the deep geological disposal of solid radioactive wastes. These dose rates can be compared with the threshold dose rates at which significant deleterious effects have been observed in field and laboratory observations. This provides a general indication of whether effects on ecosystems could be observable, but does not quantify the level of those effects. To address this latter issue, two indicator organisms were identified and exposure-response relationships were developed for endpoints of potential interest (mortality in conifers and the induction of skeletal malformations in rodents irradiated in utero). The bioaccumulation, dosimetry and exposure-response models were implemented and used to evaluate the potential significance of radionuclide releases from a proposed deep geological repository for radioactive wastes in France. This evaluation was undertaken in the context of a programme of assessment studies being performed by the Agence nationale pour la gestion des déchets radioactifs (ANDRA).

Animals↗

Fibroblast mitogenic activity of lung lavage fluid from infants with chronic lung disease of prematurity.

BACKGROUND: Lung fibrosis is thought to be important in chronic lung disease of prematurity (CLD). METHODS: Fibroblast proliferative activity was assessed in 207 bronchoalveolar lavage fluid (BALF) samples from 43 infants. Sixteen developed CLD (birth weight 765 g (630-1230), gestation 26.5 weeks (23-29)), 18 developed respiratory distress syndrome (RDS) (birth weight 1415 g (430-4160), gestation 31 weeks (23-39)), and nine control infants (birth weight 2110 g (900-3720), gestation 32 weeks (26-41)) received mechanical ventilation for non-pulmonary reasons. RESULTS: The fibroblast proliferative activity relative to 10% fetal calf serum was 64-75% in infants with CLD, 55-86% in the RDS group, and 42-68% in control infants during the first 5 weeks of life. Only at day 3 was there a difference between the groups (CLD 72% v control 42%, p < 0.01; RDS 63% v control 42%, p < 0.05). With the use of neutralising antibodies, platelet derived growth factor BB (PDGF-BB) and epidermal growth factor were undetectable, and insulin-like growth factor I (IGF-I) accounted for 14% (p < 0.05) and 11% (p < 0.005) of BALF mitogenic activity from the RDS and CLD groups respectively. CONCLUSIONS: The mitogenic activity of BALF was similar in the three groups studied and was only partially accounted for by IGF-I. Growth factors other than PDGF-BB and IGF-I contribute significantly to this process.

Bronchoalveolar Lavage Fluid↗

Humeral osteonecrosis leading to the early detection of a bronchial carcinoma.

The new Ionising Radiation (Medical Exposure) Regulations 2000 (IR (ME)ER) were implemented in January 2001. These regulations state that "the referrer must record in the patient's notes that a radiograph was taken and what it showed". As a result it is now incumbent upon the orthopaedic surgeon to document formally the findings of all requested radiographs. We present a case in which a left upper bronchial carcinoma was detected initially on a radiograph of the left shoulder. It highlights the importance of careful examination of the entire radiographic image and the documenting of the findings.

Humans↗

Redislocation of the shoulder during the first six weeks after a primary anterior dislocation: risk factors and results of treatment.

BACKGROUND: After an anterior dislocation, shoulder instability may occur with disruption of the soft-tissue or osseous restraints, leading to early redislocation. The aim of the present study was to clarify the risk factors for this complication within the first six weeks after a first-time anterior traumatic dislocation and to assess the outcome of treatment with immediate operative stabilization. METHODS: A three-year, prospective, observational cohort study of 538 consecutive patients with a first-time anterior dislocation of the shoulder was carried out. Reassessment of shoulder function was performed at a dedicated shoulder clinic, and suspected early redislocations were assessed with additional radiographs. All medically fit patients with a confirmed acute redislocation were treated with repeat closed reduction under anesthesia. Patients with unstable reductions were treated operatively. Functional and radiographic assessment of outcome was carried out during the first year after dislocation. RESULTS: Seventeen (3.2%) of the 538 patients sustained an early redislocation within the first week after the original dislocation. Patients at increased risk of early redislocation included those who sustained the original dislocation as the result of a high-energy injury (relative risk = 13.7), those who had a neurological deficit (relative risk = 2.0), those in whom a large rotator cuff tear occurred in conjunction with the dislocation (relative risk = 29.8), those in whom the original dislocation was associated with a fracture of the glenoid rim (relative risk = 7.0), and those who had a fracture of both the glenoid rim and the greater tuberosity (relative risk = 33.5). Following operative reconstruction, the outcome at one year after the injury was favorable in terms of function, general health, and radiographic findings. None of the patients had a redislocation or symptoms of instability at one year. CONCLUSION: All patients who have substantial pain, a visible shoulder deformity, or restriction of movement at one week after reduction of a first-time dislocation should be evaluated with repeat radiographs to exclude a redislocation. Patients in whom this complication develops usually have either (1) severe disruption of the soft-tissue envelope due to a large rotator cuff tear or (2) disruption of the normal osseous restraints to dislocation due to either an isolated fracture of the glenoid rim or fractures of both the glenoid rim and the greater tuberosity. Early operative stabilization is justified for patients in whom the dislocation is associated with these coexisting conditions and who have evidence of gross instability.

Adult↗

Osteoid osteoma of the distal humerus mimicking tennis elbow.

Osteoid osteoma is an uncommon bony neoplasm which rarely occurs in the elbow region. We present a case in a sixteen year old male whose symptoms were suggestive of lateral epicondylitis, or tennis elbow, and he had been treated as such for a period of eighteen months. CT scan and isotope bone scan showed typical features of osteoid osteoma and his symptoms resolved rapidly following excision of the lesion. Tennis elbow is rare in the adolescent age group, and other diagnoses should be excluded in cases where the clinical findings are suggestive of this condition.

Adolescent↗

DGT as an in situ tool for measuring radiocesium in natural waters.

The application of diffusive gradients in thin-films (DGT) samplers for the measurement of cesium radionuclides in solution, using an ammonium molybdophosphate (AMP) binding agent, was tested under both laboratory and field conditions. In the former they proved able to reproduce known 134Cs concentrations (60 Bq L(-1)) with a high degree of accuracy and precision over periods up to approximately 1 d, in freshwaters over a wide range of pH and temperature, and in saline water. In field trials in a freshwater lake receiving nuclear power station discharges, mean concentrations of 137CS (47-61 mBq L(-1)) were measured over periods from 5 d to 1 month. These agreed, within error, with mean concentrations determined from grab samples but rigorous field validation of long-term (month) deployments of DGT devices proved impossible using conventional sampling procedures, due to loss of 137Cs to container walls. Identified limitations of the DGT technique included probable AMP degradation over longer periods and calibration problems if large changes in temperature and concentration occurred together. Potential limitations due to biofilm growth were considered not to be significant. Despite the limitations, the technique appears to measure concentrations accurately for deployment times of 1 month or less. It has several advantages over traditional sampling methods for monitoring radionuclides in the solution/dissolved phase, including its simplicity, provision of time-averaged mean concentrations, and automatic in-situ concentration onto a medium with ideal counting geometry for gamma spectrometry.

Cesium Radioisotopes↗

A new-generation stable inducible packaging cell line for lentiviral vectors.

We have successfully generated and characterized a stable packaging cell line for HIV-1-based vectors. To allow safe production of vector, a minimal packaging construct carrying only the coding sequences of the HIV-1 gag-pol, tat, and rev genes was stably introduced into 293G cells under the control of a Tet(o) minimal promoter. 293G cells express the chimeric Tet(R)/VP16 trans-activator and contain a tetracycline-regulated vesicular stomatitis virus protein G (VSV-G) envelope gene. When the cells were grown in the presence of tetracycline the expression of both HIV-1-derived and VSV-derived packaging functions was suppressed. On induction, approximately 50 ng/ml/24 hr of Gag p24 equivalent of vector was obtained. After introduction of the transfer vector by serial infection, vector could be collected for several days with a transduction efficiency similar or superior to that of vector produced by transient transfection both for dividing and growth-arrested cells. The vector could be effectively concentrated to titers reaching 10(9) transducing units/ml and allowed for efficient delivery and stable expression of a GFP transgene in the mouse brain. The packaging cell line and all vector producer clones described here were shown to be free from replication-competent recombinants, and from recombinants between packaging and vector constructs that transfer the viral gag-pol genes. The packaging cell line and the assays developed will advance lentiviral vectors toward the stringent requirements of clinical applications.

Animals↗

New manzamine alkaloids with potent activity against infectious diseases.

The isolation of the new enantiomers of 8-hydroxymanzamine A (1), manzamine F (2), along with the unprecedented manzamine dimer, neo-kauluamine from an undescribed genus of Indo-Pacific sponge (family Petrosiidae, order Haplosclerida) is reported. The relative stereochemistry of neo-kauluamine was established through detailed analysis of NOE-correlations combined with molecular modeling. The significance of the manzamines as in vivo antimalarial agents with superior activity to the clinically used drugs artemisinin and chloroquine is discussed along with the activity in vitro against the AIDS-opportunistic infectious diseases tuberculosis and toxoplasmosis. Reexamination of the sponges identified as Prianos, and Pachypellina, in earlier publications has confirmed that these are members of the same genus as the sponge described here, but differ at the species level.

Animals↗

E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors.

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

Adenoviridae↗