Emergency care in general practice. General practitioners should be trained in cardiopulmonary resuscitation.
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Cardiopulmonary Resuscitation↗
Biomedical subjects
P Jones
Publications and source records attributed to P Jones.
Ductin--a proton pump component, a gap junction channel and a neurotransmitter release channel.
Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H(+)-ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8-kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane alpha-helices, which together may form a four-helix bundle. In both the V-ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction-like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre-synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes.
Amino Acid Sequence↗
Percutaneous balloon pericardiotomy: a double-balloon technique.
We describe a double-balloon technique for performing a percutaneous balloon pericardiotomy. This technique was employed when the large, single dilation balloon customarily used for this procedure failed to fully inflate across the parietal pericardium. Two smaller balloons were advanced through the same skin tract and simultaneously inflated, thus producing an adequate pericardial window. This double-balloon technique allowed for the more secure anchoring of the balloons across the pericardium and for the delivery of greater dilation pressures.
Adenocarcinoma↗
Expression of the human gene encoding urokinase plasminogen activator receptor is activated by disruption of the cytoskeleton.
The transition of a stationary cell to a motile cell is associated with the breakdown of the cytoskeleton and expression of enzymes responsible for the degradation of the extracellular matrix. Reverse transcription PCR was used to address the question of whether disruption of the microfilament and microtubule systems is a signal for the increased expression of the urokinase plasminogen activator receptor (uPAR), a key molecule involved in extracellular matrix degradation. Disruption of the cytoskeleton of human fibroblasts with cytochalasin B (1 x 10(-5) M or 1 x 10(-7) M), colchicine (1 x 10(-5) M or 5 x 10(-7) M), or nocodazole (1 x 10(-6) M) resulted in major increases in the levels of uPAR mRNA with smaller increases in uPAR protein levels. Both cycloheximide and alpha-amanitin inhibited the increase in uPAR mRNA levels, demonstrating the requirement for the de novo synthesis of a short-lived protein for transcriptional activation. In contrast to normal fibroblasts, treatment of the metastatic cell line HT1080 with either cytochalasin B or colchicine produced little change in the high levels of uPAR mRNA expressed in these cells. These data suggest that cytoskeletal disruption may contribute to cell migration by signaling an increase in uPAR synthesis.
Amanitins↗
Propofol and chemotherapy-induced emesis.
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Antiemetics↗
Analysis of the expression and secretion of isotypes of sheep B cell immunoglobulins with a panel of isotype-specific monoclonal antibodies.
Monoclonal antibodies to sheep light chain, IgM and IgG were produced and used to assess total immunoglobulin (Ig) synthesis by sheep B cells in culture and antibodies to specific antigens. By using these antibodies in a dual fluorescence-activated cell sorting analysis of sheep efferent lymph B lymphocytes the percentage change in surface Ig isotype of B lymphoblasts from IgM to IgG after the antigenic stimulation of the local lymph node was measured. An extension of this analysis to paired blood and afferent or efferent lymph B cells made it possible to investigate the recirculation characteristics of B cells expressing different Ig isotypes.
Animals↗
A comparison between solid phase extraction and supercritical fluid extraction for the determination of fluconazole from animal feed.
The application of supercritical fluid extraction with carbon dioxide and modified carbon dioxide for the determination of fluconazole from an animal feed was studied. A fractional factorial design approach was used to examine the significant experimental variables for quantitative extraction of fluconazole. Gas chromatography with either flame ionisation or mass selective detection was used for quantitation of the extracts. The results indicated that modifier (methanol) had the greatest effect on the recovery of fluconazole from the animal feed.
Animal Feed↗
Morbid risk of schizophrenia for relatives of patients with cannabis-associated psychosis.
Twenty-three patients admitted with acute psychosis who were cannabis positive on urinary screening were each matched, with respect to sex, with two psychotic controls who screened negatively for all substances. The lifetime morbid risk of psychiatric disorder was estimated among the first degree relatives of cases and controls, using RDC-FH criteria to define diagnoses, and Weinberg's shorter method of age correction. The cases had a significantly greater familial morbid risk of schizophrenia (7.1%) than the controls (0.7%), while the risks of other psychoses, and of non-psychotic conditions were similar. The same pattern of familial risk was evident when the analysis was restricted to patients with DSM-III schizophrenia. The data suggest that the development or recurrence of acute psychosis in the context of cannabis use may be associated with a genetic predisposition to schizophrenia.
Adult↗
A serum-sensitive, sialyltransferase-deficient mutant of Neisseria gonorrhoeae defective in conversion to serum resistance by CMP-NANA or blood cell extracts.
A stable, sialyltransferase-deficient mutant of Neisseria gonorrhoeae strain F62 totally defective in CMP-NANA-dependent lipopolysaccharide (LPS) sialylation was isolated by insertion mutagenesis with transposon Tn 1545-delta 3 and screened for unlabelled colonies following incubation with CMP-14C-NANA. In contrast to the parental strain which became serum resistant on incubation with CMP-NANA or blood cell extracts, the mutant, JB1, remained serum sensitive. French press extracts of strain F62 catalysed LPS sialylation, but corresponding extracts of the mutant were inactive. Five LPS components were detected by SDS-PAGE in the parental strain. Five components of the same Mr were also found in the mutant. Three identical components were detected by Western blotting using MAb 3F11, which recognizes the Gal beta 1-4GlcNAc groups in the conserved LPS components of F62 which can be sialylated. The mutant, JB1, is therefore deficient in the sialyltransferase that is essential for both LPS sialylation and conversion of serum-sensitive gonococci to serum resistance by either CMP-NANA or blood cell extracts. No evidence was obtained for an LPS sialylation pathway by blood cell extracts that is independent of CMP-NANA.
Antibodies, Monoclonal↗
Detection of oxidants in uremic plasma by electron spin resonance spectroscopy.
Depletion of antioxidants and the presence of products of free radical damage in plasma suggest that oxidative stress is increased in uremia. We have developed an application of electron spin resonance spectroscopy, and used this method to show that a stable oxidizing component or components of plasma accumulate in uremia. No oxidizing activity was detectable in plasma from subjects with normal renal function. The oxidant was detected by its capacity to oxidize the spin trap 3,5-dibromo-4-nitrosobenzene sulphonate (DBNBS). The oxidant was dialyzable from plasma, had an upper molecular weight limit of about 3,000 Daltons and was stable over many months. Physiological plasma concentrations of vitamin C, a water soluble congener of vitamin E and reduced glutathione were unable to inhibit the oxidizing capacity of uremic plasma. Thus, uremia is associated with accumulation of an endogenous oxidizing activity at much higher concentrations than in subjects with normal renal function.
Adult↗
The risk of suicide in people with haemophilia who are HIV infected.
The incidence of suicide in the HIV infected haemophilic population of the United Kingdom is low. Between 1985, when most patients were tested for HIV infection, and 1993 3 possibly HIV-related suicides were reported to Haemophilia Centre Directors. It is argued that haemophilia comprehensive care may contribute to reducing some of the factors associated with suicide risk, and thus be a reason for this low incidence. It is suggested that the pattern of health care delivery developed for the haemophilia community might serve as a template for those treating others with HIV infection.
Adult↗
GSTM1 and CYP2D6 genotype frequencies in patients with pituitary tumours: effects on P53, ras and gsp.
We describe studies to determine if susceptibility to pituitary tumours is associated with the putatively high risk GSTM1 null and CYP2D6 EM genotypes. Frequency distributions of these genotypes were similar in cases and controls though the frequency of CYP2D6 PM and GSTM1 B tended to be lower (P = 0.072 and P = 0.095 respectively) in the tumour group. Immunopositivity for p53 was found in 18/97 tumours. In these samples GSTM1 null (39%) and CYP2D6 EM (56%) frequencies were not different to those in controls. The frequencies of CYP2D6 PM and GSTM1 B in the p53 immunonegative tumours tended to be lower (P = 0.055 and P = 0.1185 respectively) than in controls. Mutations in gsp and ras were studied using the polymerase chain reaction and allele specific oligonucleotide analysis. Eight of 19 somatotrophinomas demonstrated mutations in gsp; frequencies of GSTM1 null and CYP02D6 EM were similar to controls. No ras mutations were identified in 55-tumour studies. The data indicate the GSTM1 null and CYP2D6 EM genotypes are not associated with altered expression of p53 or, mutation of gsp and ras in these adenomas and, suggest the CYP2D6 PM genotype is associated with a reduced risk of pituitary adenomas and, that GSTM1*B confers greater protection than GSTM1*A.
Adult↗
Can activity monitors be used to assess compliance with walking programmes in the elderly?
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Aged↗
Assessment of GH status in acromegaly using serum growth hormone, serum insulin-like growth factor-1 and urinary growth hormone excretion.
OBJECTIVE: It is still not clear what is the most suitable method for monitoring progress of acromegaly. The aim of this study was to assess the relative merits of serum GH, serum IGF-I and urinary GH (uGH) excretion in the follow-up of acromegalic subjects. SUBJECTS AND METHODS: Thirty-six acromegalic patients each had a GH day series performed consisting of five serum GH measurements, together with an estimate of serum IGF-I and uGH. The first sample taken for serum GH was fasting (basal) whilst the third (1430h) was arbitrarily chosen as a random value. uGH was measured from two overnight collections and the mean value used for subsequent data analysis. MEASUREMENTS: Serum GH and IGF-I were measured by radioimmunoassay whilst uGH was estimated by an immunoradiometric assay using commercially available reagents. RESULTS: There is a highly significant linear correlation between serum GH and IGF-I following log transformation of these two variables (r = 0.85; P < 0.0001). Analysis of the raw data shows that the relation is in fact curvilinear rendering IGF-I less useful as a surrogate for integrated GH secretion at high levels of serum GH. There is a strong linear correlation between both a singleton basal serum GH and uGH (r = 0.78; P < 0.001) and the mean of five measurements (day series) and uGH (r = 0.81; P < 0.0001). Both uGH and IGF-I are excellent predictors of those patients with persistent elevation of serum GH, identifying 95 and 96% respectively with serum GH > 5mU/l. We have identified a number of patients, however, with persistent elevation of IGF-I in the presence of serum GH < 5mU/l and normal uGH. Until the significance of these findings with respect to long-term outcome is known, serum GH should continue to be used in the follow-up of these patients. An alternative, which reflects integrated overnight GH secretion, is uGH which is convenient and easy to collect as an outpatient and correlates strongly with serum GH. CONCLUSION: Acromegalic patients can be conveniently followed on an outpatient basis using a combination of uGH and serum IGF-I. Measurements of serum GH can be reserved for those with discrepant results.
Acromegaly↗
Assessment of GH status in adults with GH deficiency using serum growth hormone, serum insulin-like growth factor-I and urinary growth hormone excretion.
OBJECTIVES: The benefits of treating adults with GH deficiency are now well recognized although the criteria for deciding which patients to treat are still not clear. At present the 'gold standard' is the insulin stress test (IST) which is unpleasant and potentially dangerous, particularly in patients with hypopituitarism. The aim of this study was to determine whether alternative methods of assessing GH status are reliable in predicting GH deficiency. SUBJECTS AND METHODS: Forty-four patients with unequivocal GH deficiency (peak IST < 2 mU/l) and 17 with partial deficiency (peak IST 2-10 mU/l) were studied. Each patient was assessed clinically with respect to the number of other pituitary axes affected and biochemically with an estimate of urinary GH excretion (uGH) and serum IGF-I. These markers were then related to GH status as defined by insulin stress testing. MEASUREMENTS: Insulin stress tests were performed using 0.1 units/kg i.v. and accepted with a blood glucose < 2 mmol/l. Serum GH and IGF-I were measured by radioimmunoassay whilst uGH was estimated by an immunoradiometric assay using commercially available reagents. uGH was estimated from the mean of two overnight urine collections which consisted of all urine passed from last voiding through to the first morning sample. RESULTS: The presence of unequivocal GH deficiency (peak IST < 2 mU/l) was predictable if 2 or more other pituitary axes were affected (90%). uGH declined significantly with the level of peak IST response (P < 0.001) and almost so with the number of other deficient hypothalamic-pituitary axes affected (P = 0.057). Thus, uGH accurately reflected GH status and showed good separation from normal controls in patients less than 40 years (specificity 79%) and between 40 and 60 years (specificity 67%). Above this age the method is less specific (36%). Patients excreted significantly less GH than controls in all three age groups (P < 0.01). Subnormal levels of IGF-I were strongly predictive of unequivocal GH deficiency (91% with subnormal IGF-I have a peak IST GH < 2 mU/l) although a normal value does not reliably exclude the diagnosis. CONCLUSIONS: A diagnosis of adult GH deficiency can be reliably made without the need for an insulin stress test by using a combination of low urinary GH excretion, subnormal IGF-I levels and clinical assessment with regard to the number of other pituitary axes affected.
Adolescent↗
The etiology of bladder cancer--are there any new clues or predictors of behavior?
It is well documented that the etiology of bladder cancer involves environmental factors. Most chemical carcinogens probably affect the urothelial cells via their presence in the urine. As an important cofactor, cell proliferative activity may be increased by urinary bladder infection, irritation by bladder stones or through the action of a variety of endogenously produced direct acting chemicals or agents. Among the known causative factors, avoidable major ones are occupational exposure to certain chemicals such as benzidine and 4-aminobiphenyl, cigarette smoking and bilharzial infection, which could be eradicated by a combination of praziquantel, antihelminth therapy, education and improvements in social welfare. An anticarcinogenic drug, cyclophosphamide, used as an immunosuppressive agent also seems to be associated with a high risk of idiopathic induction of bladder cancer and physicians should therefore pay particular attention to its diverse effects when considering its prescription. In contrast to the above, the consumption of coffee and tea including artificial sweeteners is now thought unlikely to be major risk. So far there is no good biochemical tool to predict individual exposure to bladder carcinogens/or relative risk of bladder cancer development. However, acetylation capacity can be applied to assess susceptibility to carcinogenic amines in people exposed in their working environment. Progress in molecular biological analysis will hopefully bring to light etiology-specific DNA damage in the bladder tumors and prove useful for prediction of tumor behavior in the near future.
Diet↗
Impact of functional severity on self concept in young people with spina bifida.
This study examines the relationship between medical and functional severity of disability and levels of self esteem and self concept in 79 young people with spina bifida. Greater feelings of global self worth and of self esteem in physical appearance were associated with greater severity of disability. This was only in part an effect of lower IQ among the most disabled young people. Many of the least disabled had marked impairment of self esteem. Analysis of the impact of individual aspects of disability confirmed the association between increased self esteem in physical appearance and global self worth, and diminished functional ability. Academic self ratings, however, were higher in the less disabled. Hydrocephalus and continence appeared to have minimal effect on self esteem. The relationship between severity of disability in spina bifida and self concept is complex and mediated by a range of factors. It is incorrect to assume that the psychological impact is less in the mildly disabled young person.
Adolescent↗
Electron spin resonance spectroscopic demonstration of the generation of reactive oxygen species by diseased human synovial tissue following ex vivo hypoxia-reoxygenation.
OBJECTIVE: To apply an electron spin resonance (ESR) spectroscopic technique as a means of determining the oxidising capacity of reactive oxygen species produced during hypoxia and reoxygenation of diseased human synovial tissue. METHODS: Twenty four specimens of fresh synovial tissue were obtained from patients undergoing primary total knee joint replacement and graded according to the degree of inflammation present. Tissue samples were subjected to an ex vivo hypoxia-reoxygenation cycle in the presence of the nitroso based spin trap, 3,5-dibromo-4-nitrosobenzene sulphonate. The degree of oxidation of the spin trap to a stable free radical was determined and followed with time. Control samples were subjected to hypoxia only. RESULTS: The results indicate that the oxidising capacity of reactive oxygen species produced by human synovial tissue varies with the degree of inflammation present. Only the more inflamed specimens, from both rheumatoid arthritis and osteoarthritis patients, demonstrated increased production of reactive oxygen species when subjected to a hypoxia-reoxygenation cycle. This change was reduced by both competitive and non-competitive inhibitors of the endothelial based enzyme xanthine oxidase. The relative concentration of reactive oxygen species generated by the synovial tissue samples correlated with the mean capillary density of the specimens. CONCLUSION: This study supports the hypothesis of movement induced hypoxicreperfusion injury of the chronically inflamed joint by demonstrating the generation of reactive oxygen species within inflamed human synovium following an ex vivo hypoxia-reoxygenation cycle. Evidence is presented that the microvascular endothelial based enzyme xanthine oxidase is the predominant source of ESR detectable oxidising species in inflamed synovial specimens exposed to hypoxia-reoxygenation.
Adult↗