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Biomedical subjects

M John

Publications and source records attributed to M John.

At least 19 recordsLinked to original sources

Rupture of the subscapularis tendon (isolated or in combination with supraspinatus tear): when is a repair indicated?

Ruptures of the subscapularis tendon, isolated or combined, are rare, and the treatment modalities are controversial. Of 1345 patients who underwent rotator cuff repair in a 7-year period, 73 had either an isolated rupture of the subscapularis or a subscapularis rupture combined with rupture of the supraspinatus. All reconstructions were performed through a deltopectoral approach. Reinsertion of the subscapularis was combined with reconstruction of the supraspinatus in 32 patients. Of the patients, 63 (86%) were re-examined at a mean follow-up of 35 months. The modified Constant score improved from 62% preoperatively to 91% at follow-up. Isolated or combined reconstructions did not result in significant differences with respect to the Constant score. Of the patients, 62 (98%) were satisfied with the operation. Rerupture was found by ultrasound in 8 subscapularis tendons (13%) and 4 supraspinatus tendons (13%). The rerupture rate showed a significant correlation with the Goutallier stage of fatty degeneration and the interval between injury and operation.

Adult↗

ESPEN Guidelines on Enteral Nutrition: Cardiology and pulmonology.

These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They have been discussed and accepted in a consensus conference. EN by means of oral nutritional supplements (ONS) or tube feeding (TF) enables nutritional intake to be maintained or increased when normal oral intake is inadequate. No data are yet available concerning the effects of EN on cachexia in CHF patients. However, EN is recommended to stop or reverse weight loss on the basis of physiological plausibility. In COPD patients, EN in combination with exercise and anabolic pharmacotherapy has the potential to improve nutritional status and function. Frequent small amounts of ONS are preferred in order to avoid postprandial dyspnoea and satiety as well as to improve compliance.

Cardiology↗

Delivering results to clients: a question of satisfying needs or desires?

Demand for genitourinary (GU) medicine services is outstripping supply. Improving efficiency can modulate the supply side of the equation, e.g. decreasing the number of clients having to return for their results. This survey explored how clients at two central London GU medicine clinics would like to receive their results and their views were reflected against what was offered by London GU medicine clinics. There was a significant difference between the result delivery services that the clients wanted and what the clinics provided (P <0.0001, chi(2)). Of the clients, 92% wanted to know their results regardless of outcome whereas 22% of London clinics would only inform clients of positive results. This study questions the importance and feasibility of patient choice, an important aspect of the National Strategy for Sexual Health and HIV. Clinics may not individually be able to provide choice but between them, they do provide a wide range of alternatives for the client.

HIV Infections↗

[COPD in the year 2005].

COPD is a widespread illness with an increasing prevalence and mortality rate. Current knowledge of its pathophysiology has it that COPD is not simply limited to the lungs, but must be understood as a systemic inflammatory reaction. The ATS/ERS guideline goes beyond the recommendations of the GOLD guideline, and takes account of the peculiarities of the European and North American healthcare systems (www.ersnet.org). In this context, the role of inhaled steroids, which is currently still under lively discussion, has to be revisited. Additional possible approaches include the administration of appetite stimulants and dietary measures, and the application of iron or erythropoietin. The TORCH study--currently the largest ongoing COPD study--is investigating the influence of inhaled glucocorticoids and long-acting beta2 agonists on mortality.

Administration, Inhalation↗

[Bronchial artery embolisation using platinum coils in 52 patients with severe pulmonary hemorrhage].

BACKGROUND: Severe pulmonary hemorrhage ist life-threatening. One of the treatment options in case of severe pulmonary hemorrhage is bronchial artery embolisation (BAE) with different embolisation materials. PATIENTS AND METHODS: Efficacy of BAE using platinum coils was investigated retrospectively in a total of 52 patients. 22 suffered from benign lung diseases (angiodysplasia, inflammation, bronchiectasia) and 30 patients had lung cancer (lung metastases in two cases). RESULTS: Primary hemostasis was achieved in over 90 % of the patients (47 of 52). Recurrent BAE was necessary in 23 % of patient with benign etiologies and in 50 % of the tumor patients. Comparing the results of the lung cancer patients with a control group from a teaching hospital without BAE we found survival-advantages for those patients treated with BAE. CONCLUSION: Our results underline the usefulness of BAE in severe pulmonary hemorrhage.

Adult↗

[Comparison of rheumatic and post-traumatic elbow joints after total elbow arthroplasty. Comprehensive and specific evaluation of clinical picture, function, and quality of life].

BACKGROUND: Patients with elbow destruction due to rheumatoid arthritis (RA) or trauma (PT) were compared to population-based normative data and to each other after total elbow arthroplasty. PATIENTS AND METHODS: Pain, function, and biopsychosocial health were multidimensionally assessed by the generic Short Form 36 (SF-36), the condition-specific Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), and the Patient Related Elbow Evaluation form (PREE) instrument and analyzed by uni- and multivariate methods. RESULTS: Compared to normative values, the examined 59 RA patients were significantly affected in the function scales of the SF-36 and in all DASH scales. The 20 PT patients were worse than the norm only in the DASH function. Function was lower in RA than in PT in the SF-36 scales and in the DASH (RA: 44.4, PT: 70.3, p<0.001). This difference was less distinct in the PREE. CONCLUSION: Total elbow arthroplasty led to a pain-free outcome and normal quality of life, but failed to restore complete function. Functional deficits were larger in the RA patients and could also be measured by the SF-36, possibly due to polyarticular affection.

Aged↗

P-selectin glycoprotein ligand-1 (PSGL-1) is up-regulated on leucocytes from patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by a dysregulated recruitment of circulating leucocytes into the lung which is associated with the onset and progress of the disease. P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on leucocytes and plays an essential role in primary leucocyte-endothelial cell adhesive contacts. The present study investigated if PSGL-1 is up-regulated on leucocytes of COPD patients. Peripheral blood samples were collected from COPD patients as well as controls (smoking, nonsmoking volunteers) and subjected to analysis of PSGL-1 expression on leucocytes, i.e. neutrophils, eosinophils, monocytes and lymphocytes by flow cytometry. No significant difference was observed between healthy nonsmoking and healthy smoking control subjects. In contrast, PSGL-1 expression was found to be significantly increased on the surface of all four leucocyte populations in COPD patients compared to both control groups. The finding that PSGL-1 surface expression is up-regulated on leucocytes of COPD patients as compared to leucocytes of controls suggests PSGL-1 as a potential target for anti-inflammatory treatment.

Adult↗

Short term use of octreotide in acromegaly.

A 44-year gentleman with acromegaly underwent transphenoidal excision of pituitary macroadenoma followed by radiotherapy. Since he had poor glycemic control necessitating multiple insulin doses, he was started on subcutaneous octreotide. With this, his blood sugars came under control rapidly and insulin could be withdrawn fully. This case report highlights the use of octreotide in a specific clinical situation in acromegaly to improve the quality of life.

Acromegaly↗

E-MSD: an integrated data resource for bioinformatics.

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD 'atlas pages' show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

Algorithms↗

Preeclampsia is associated with loss of neuronal nitric oxide synthase expression in vascular smooth muscle cells of the human umbilical cord.

AIMS: Umbilical blood vessels are not innervated and regulation of blood flow to the placenta must depend on structural changes and the effect of vasoactive factors. Failure to achieve these adaptations may result in reduced fetoplacental perfusion. The purpose of this study was to determine whether neuronal nitric oxide synthase (nNOS) is expressed in human vascular smooth muscle cells (VSMCs) of the fetoplacental circulation. nNOS has been described as a non-endothelial NOS counterregulating vasoconstriction only in the VSMCs of animal models. Therefore, we investigated nNOS expression in the fetoplacental unit from preeclamptic and healthy pregnancies. METHODS AND RESULTS: We investigated nNOS regulation by immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain reaction analysis. nNOS activity was determined by measuring the conversion of L-3H-arginine to L-3H-citrulline. nNOS expression was revealed only in VSMCs of the human umbilical veins, but not in umbilical arteries. A more direct assessment of nNOS activity showed that a small, but consistent amount of nNOS is present in the denuded media of the umbilical vein. In VSMCs of the umbilical veins during preeclampsia a total loss of nNOS protein expression and a significant decrease in mRNA expression were seen. CONCLUSIONS: Loss of nNOS expression is associated with preeclampsia. It may alter the regulation of blood flow in the fetal and maternal placental vasculature in preeclampsia. However, the impact of NO produced by nNOS on the vascular tone of umbilical veins remains to be elucidated.

Adult↗

Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling.

In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.

Cluster Analysis↗

E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

Animals↗

Muscle injury in organophosphorous poisoning and its role in the development of intermediate syndrome.

Muscle injury and its role in the development of Type II paralysis was studied in 25 patients with acute organophosphate poisoning. All patients were assessed for severity of poisoning at admission and through the course of poisoning for the development and duration of intermediate syndrome (IS) (Type II paralysis). Blood levels of acetylcholinesterase, creatine kinase, creatine kinase MM, LDH and LDH5 were estimated through the course of the poisoning. Of the 25 patients, 22 were severely poisoned and 3 had mild to moderate poisoning. Severely poisoned patients had a significantly greater rate of developing intermediate syndrome (17/22) (P = 0.026). Type I paralysis and fasciculations occurred in 76 and 70.5% of patients who developed intermediate syndrome, in comparison to 38 and 50%, respectively, of those who did not develop intermediate syndrome. Weakness developed in the same groups of muscles in both Types I and II paralysis but was of longer duration in patients who developed Type II paralysis. Acetylcholinesterase was inhibited > 90% throughout the course of poisoning with greater inhibition in patients with longer duration intermediate syndrome. Muscle injury was seen in all patients beginning at admission, peaking over the first 5 days and then declining over the next 5 days. Temporal profiles of blood muscle isoenzymes showed significantly greater muscle injury in those patients with greater severity of poisoning at admission, those who developed intermediate syndrome and in patients with longer duration intermediate syndrome. The findings of this study suggest that Types I and II paralysis in organophosphate poisoning are not separate syndromes but a clinical continuum determined by the severity of poisoning. The magnitude of organophosphate exposure and of muscle injury during the cholinergic crises appears to determine the occurrence and severity of intermediate syndrome.

Acetylcholinesterase↗

Signaling of the human calcium-sensing receptor expressed in HEK293-cells is modulated by protein kinases A and C.

In this study, the human calcium-sensing receptor (CaR) stably expressed in HEK293 cells was investigated with regard to the phosphorylation-induced desensitization of its signaling pathway. The receptor is known to activate the phospholipase C/inositol-1,4,5-trisphosphate (IP 3 ) signaling cascade, thus stimulating protein kinase C (PKC). In contrast, the adenylylcyclase/cAMP signaling pathway that activates protein kinase A (PKA) is believed to be coupled to the receptor via an inhibitory G-protein. We elucidated the roles of PKC and PKA by measuring Ca 2+o -stimulated accumulation of total inositol phosphates and by individually and simultaneously inhibiting the two kinases pharmacologically in HEK293 cells, which stably expressed the human CaR. Pharmacological inhibition of PKC resulted in a 5-fold enhancement of IP 3 signaling, whereas blocking PKA had almost no effect. IP 3 signaling activity increased even more (10-fold) however, when the two kinases were inhibited simultaneously. Apart from validating the role of PKC as a potent down-regulator of signaling of the human CaR in this cell system, this study suggests that both kinases synergize in inhibiting Ca 2+o -stimulated IP 3 signaling in CaR-transfected HEK293 cells.

Calcium Chloride↗