Effect of obesity in patients with coronary artery disease.
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Biomedical subjects
Publications and source records attributed to J Garvey.
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The aim of this systematic review was to determine the efficacy and potential benefits of enteral nutritional support [oral nutritional supplements (ONS) or enteral tube feeding (ETF)], and eicosapentaenoic acid (EPA, free acid, ethyl esters or fish oil; provided as capsules or enriched ONS or ETF) in patients with cancer. Clinical studies were identified using electronic databases, and studies were selected according to predetermined criteria. For each treatment modality (chemo/radiotherapy, surgery, and palliative care), the comparisons of interest were nutritional support vs. routine care (no nutritional support), EPA supplement (capsule or enriched ONS or ETF) vs. routine care (no supplement or standard supplement), ETF vs. parenteral nutrition (PN). The reviewed outcomes were dietary intake, anthropometry, clinical (mortality, length of hospital stay, complications, and quality of life) and haematological/biochemical (white blood cell count, serum transferrin and albumin, CD3-positive lymphocytes, and inflammatory markers). Meta-analyses were performed where possible. In patients undergoing radiotherapy, meta-analysis showed that ONS significantly increase dietary intake (381 kcal/day, 95% CI 193 to 569 in 3 RCTs) compared to routine care. In patients undergoing surgery, meta-analyses showed that ETF results in a significantly shorter length of hospital stay (1.72 fewer days, 95% CI 0.90 to 2.54 in 8 RCTs), lower incidence of any complications (OR 0.62, 95% CI 0.50 to 0.77 in 4 RCTs) and infectious complications (OR 0.67, 95% CI 0.55 to 0.82 in 11 RCTs) and lower sepsis scores (2.21 points, 95% CI 1.49 to 2.92 in 2 RCTs), but no difference in mortality (OR 0.72, 95% CI 0.40 to 1.29 in 7 RCTs) compared to PN. There was also no difference in mortality between ONS or ETF vs. routine care in patients undergoing chemotherapy/radiotherapy (OR 1.00, 95% CI 0.62-1.61 in 4 RCTs) or surgery (OR 2.44, 95% CI 0.75 to 7.95 in 4 RCTs). Individual studies of EPA supplementation as capsules showed improvements in survival, complications and inflammatory markers in patients undergoing bone marrow transplant (BMT). In palliative care patients receiving EPA-enriched ONS or capsules, there were inconsistent positive effects on survival and quality of life. In those undergoing surgery, EPA-enriched ETF had no effect. Further research is required to elucidate the clinical efficacy of enteral nutrition support, including the potential benefits of EPA supplementation, in patients with cancer.
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G protein-gated inward rectifier K+ channel subunits 1-4 (GIRK1-4) have been cloned from neuronal and atrial tissue and function as heterotetramers. To examine the inhibition of neuronal excitation by GIRKs, we overexpressed GIRKs in cultured hippocampal neurons from 18 day rat embryos, which normally lack or show low amounts of GIRK protein and currents. Adenoviral recombinants containing the cDNAs for GIRK1, GIRK2, GIRK4, and the serotonin 1A receptor were constructed. Typical GIRK currents could be activated by endogenous GABAB, serotonin 5-HT1A, and adenosine A1 receptors in neurons coinfected with GIRK1+2 or GIRK1+4. Under current clamp, GIRK activation increased the cell membrane conductance by 1- to 2-fold, hyperpolarized the cell by 11-14 mV, and inhibited action potential firing by increasing the threshold current for firing by 2- to 3-fold. These effects were not found in non- and mock-infected neurons, and were similar to the effects of muscarinic stimulation of native GIRK currents in atrial myocytes. Two inhibitory effects of GIRK activation, hyperpolarization and diminution of depolarizing pulses, were simulated from the experimental data. These inhibitory effects are physiologically important in the voltage range between the resting membrane potential and the potential where voltage-gated Na+ and K+ currents are activated; that is where GIRK currents are outward.
Branched chain DNA assay (bDNA), cytomegalovirus (CMV) antigen assay, and cerebrospinal fluid (CSF) viral culture were studied for their utility in the diagnosis of CMV polyradiculopathy and for documenting in vivo antiviral effects. CMV was demonstrated in 15 of 16 patients by bDNA assay, 15 of 16 by CMV antigen assay, and 11 of 15 by CSF culture. When clinical criteria and results of the other two assays were used as reference standards, the sensitivity of bDNA was 94% and 100% and the specificity 95.2% and 100%; the CMV antigen assay sensitivity was 94% and 100% and specificity was 85.7% and 100%. Nine (90%) of 10 patients with polyradiculopathy and follow-up CSF culture showed a drop in CMV DNA after treatment; however, only 2 (20%) improved clinically. These results suggest that bDNA and antigen assays may be useful methods for the diagnosis of CMV polyradiculopathy, but treatment failures may not be due to inadequate antiviral activity.
Coexpression in Xenopus oocytes of the inwardly rectifying guanine nucleotide binding (G)-protein-gated K channel GIRK1 with a myristoylated modification of the (putative) cytosolic C-terminal tail [GIRK1 aa 183-501 fused in-frame to aa 1-15 of p60src and denoted src+ (183-501)] leads to a high degree of inhibition of the inward G-protein-gated K+ current. The nonmyristoylated segment, src- (183-501), is not active. Although some interference with assembly is not precluded, the evidence indicates that the main mechanism of inhibition is interference with functional activation of the channel by G proteins. In part, the tail functions as a blocking particle similar to a "Shaker ball"; it may also function by competing for the available supply of free G beta gamma liberated by hormone activation of a seven-helix receptor. The non-G-protein-gated weak inward rectifier ROMK1 is less effectively inhibited, and a Shaker K channel was not inhibited. Immunological assays show the presence of a high concentration of src+ (183-501) in the plasma membrane and the absence of any membrane forms for the nonmyristoylated segment.
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A survey has been conducted of solid and ascites tumors from mice and solid tumors in rats for the presence of metallothionein or metallothionein-like protein. In most tumors, a positive identification was made on the basis of Sephadex G-75 and HPLC-DEAE chromatography followed by competitive radioimmunoassay for metallothionein. Apometallothionein was revealed in a number of tumors for the first time by comparing the Sephadex G-75 chromatographic profiles of Zn in native cytosol and Cd in cytosol incubated briefly with CdCl2 to saturate free binding sites on the protein before Sephadex G-75 chromatography. In two cases unsaturation of metallothionein was correlated with a lack of zinc in the ascites fluid which supplies the tumor with zinc.
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We have identified a myelin basic protein (MBP) isoform in mouse embryos that includes an exon upstream of the usual transcription initiation site. This isoform, embryonic-neonatal MBP (E-MBP), is expressed at the protein level in the embryonic nervous system at a time when other MBP isoforms are not detected. In addition to the central and peripheral nervous systems of the embryo and neonate, the thymus, spleen, and testes also express E-MBP at the protein level. The expression of E-MBP in cell types distinct from the nervous system strongly suggests that this MBP isoform has a role apart from the formation of myelin.
New CPR guidelines have been produced with the aim of standardising techniques throughout Europe. James Garvey examines the new guidelines and asks why so little official information has been made available to trainers on this recent update.
For those OHPs returning to study at diploma level educational approaches encouraging independent thought can present unexpected new challenges. James Garvey discusses teaching strategies in higher education and argues that it is time to get away from the formal learning situations of the past.
The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits and decreased concentrations of dopamine, homovanillic acid, and 3,4-dihydroxy-phenylacetic acid (DOPAC) and [3H]dopamine uptake in the caudate-putamen. There was an 80% reduction in tyrosine hydroxylase immunoreactive cells in substantia nigra. At 10 days following the start of MPTP administration, the activity of choline acetyltransferase in the thalamus and frontal cortex was unchanged compared with control animals. Similarly, specific [3H]QNB binding was unaltered. At 4-6 weeks following the start of MPTP treatment, choline acetyltransferase activity and [3H]QNB binding in the frontal cortex and thalamus remained unaffected. There was no evidence for cell loss in the nucleus basalis of Meynert or alteration in the intensity of staining for acetylcholinesterase. MPTP treatment of the common marmoset produces a nigrostriatal lesion. In contrast, MPTP did not alter cortical cholinergic function and was not neurotoxic to the cholinergic cells in the nucleus basalis of Meynert.
Using a technique described previously, we have applied pressure to the optic nerve of a cat sufficient to cause conduction block of the t1 response (the response of the Y optic nerve fibres). A greater pressure, usually sufficient to cause a transient block of the t2 response (the response of the X fibres), leads to degeneration of the Y axons caudal to the block. This is demonstrated by the disappearance of the t1 response in this region after 4-5 days and by the presence in electron micrographs of degenerating large (Y) fibres. Some small fibres also show degeneration, but the medium (X) fibres are largely spared. The time course of loss of response in the Y fibres is similar whether the loss is due to a pressure block or to enucleation, suggesting that the pressure block as used by us causes a disruption of the axon. If the pressure is great enough to block part of the t2 response (X fibres) there is also a similarity in time course of loss of response to that following enucleation. Both for the enucleated and the pressure-blocked cat the t2 response fails about 1 day before the t1 response. This is in apparent disagreement with the morphological findings in the literature, confirmed here, indicating an earlier degeneration of the larger fibres. The post-synaptic response in the lateral geniculate nucleus to the t1 input (the r1 response) also fails about 1 day before the t1 response. In the visual cortex the loss of the r1 response reveals more clearly than is normally possible an r2 response, the response of the X optic radiation fibres. The response in the optic nerve or tract to a bright flash of light is dominated by the response of the Y fibres. When these are blocked the response is greatly reduced.
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Platelet-associated IgG (PAIgG) can be measured on intact platelets or following platelet lysis. Measurement of PAIgG following platelet lysis may provide different or additional information compared to PAIgG measured on intact platelets. The PAIgG of lysed platelets represents "total" PAIgG, ie, IgG on the surface of platelets plus any IgG that was inside the platelet. To investigate the clinical relevance of the two types of PAIgG assay we performed a prospective study on washed platelets collected from 47 patients with idiopathic thrombocytopenic purpura (ITP). The PAIgG was measured on intact and lysed platelets using an immunoradiometric assay. Platelet-associated IgG was 2-3 times higher when measured on lysed platelets from healthy controls or patients with ITP compared to PAIgG measured on the same intact platelets. The higher level of PAIgG observed following platelet lysis was not due to the reactions not achieving equilibrium. Using lysed platelets, PAIgG was elevated on 29 of 47 samples from different ITP patients and elevated in 31 samples when measured on intact platelets. The PAIgG is invariably higher when measured following platelet lysis compared measurements made on intact platelets. Neither technique offers a diagnostic advantage over the other.
Preoperative oblique hilar tomography was used to evaluate hilar lymph nodes in 150 patients with clinically resectable bronchogenic carcinoma. CT was also used in the evaluation of mediastinal lymph nodes in 50 of these patients. Subsequently, all patients underwent mediastinoscopy and/or thoracotomy. Hilar and mediastinal nodes were evaluated for the presence of metastasis, and these findings were then correlated with the radiographic findings of oblique hilar tomography and CT. CT was found to be a reliable method for prethoracotomy staging of bronchogenic carcinoma and for selecting patients for mediastinoscopy. The sensitivity of CT for evaluation of mediastinal nodal metastasis was 83% and the specificity was 90%. Thus patients with negative mediastinal CT need not undergo mediastinoscopy prior to thoracotomy, while mediastinoscopy and biopsy should be done in patients with enlarged mediastinal nodes on CT. Oblique hilar tomography is an accurate method for evaluation of hilar adenopathy and for predicting mediastinal involvement by extrapolation.
One hundred patients with bronchogenic carcinoma had oblique hilar tomography preoperatively to evaluate the pulmonary hila. Subsequently, all of these patients underwent mediastinoscopy or thoracotomy or both. Hilar and mediastinal nodes were evaluated for the presence of metastasis. These findings were then correlated with the radiographic findings of oblique hilar tomography. We found oblique hilar tomography to be a useful method of selecting patients for mediastinoscopy. The negative predictive value of oblique hilar tomography for mediastinal involvement was 95 percent, while the positive predictive value was 75 percent. Thus, patients with negative findings on oblique hilar tomography need not undergo mediastinoscopic examination prior to thoracotomy.