QQ: waterbirth, a new beginning.
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Biomedical subjects
Publications and source records attributed to C Hall.
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Energy efficiency provides hospitals with opportunities to save costs, help the environment and improve the internal environment for staff and patients. The Government has set the health sector an energy saving target of 20%, equivalent to cuts of 60 m Pounds by 2001 and 1.2 Mt carbon dioxide. These savings can be achieved and exceeded, cost-effectively, if good practise is adopted throughout the sector. Assistance in meeting the Government's energy target and meeting good practice benchmarks is available from the Energy Efficiency Best Practise programme through BRECSU.
This study was undertaken to characterise patients without overt heart failure and with a left ventricular ejection fraction > or = 40% 2-7 days following an acute myocardial infarction. Patients with an ejection fraction > or = 40% (n = 868) had a lower prevalence of anterior myocardial infarction (p < 0.001) and lower levels of N-terminal pro-ANP (atrial natriuretic peptide) (p < 0.001) than those with ejection fraction < 40% (n = 305). Patients with ejection fraction > or = 40% had smaller left ventricular volume and mass (p < 0.001). Pro-ANP levels did not correlate significantly with left ventricular volume or ejection fraction in this group. Among patients with ejection fraction < 40%; statistically significant correlations between pro-ANP levels and both ejection fraction and left ventricular endsystolic volume were found. 64% and 61% of patients in the two groups were given thrombolytic treatment. In this study, most patients with acute myocardial infarction had an ejection fraction > or = 40%. Pro-ANP levels were not correlated with the ejection fraction or left ventricular volume. Approximately two thirds of the patients received thrombolytic treatment.
Measurement of plasma levels of natriuretic peptides are now in clinical use in adult patients with heart failure. Experiences in adult medicine cannot be extended to paediatric cardiology due to important physiological differences between adults and children. The haemodynamic background of heart failure in children with congenital heart disease is diverse, and there is no relevant functional or echocardiographic grading system. The authors present results from published studies and summarizes the results of a research project concerning the clinical potential of N-terminal proatrial natriuretic peptide (Nt-proANP) in paediatric cardiology. Peptide levels in newborn children with or without disease are not fully clarified. In children above three months of age, an elevated Nt-proANP value strongly indicates haemodynamic imbalance. This may be important in the follow-up of children with congenital heart disease. A normal value does not exclude the presence of heart disease. A case report illustrates the clinical use of Nt-proANP, and peptide levels in different haemodynamic situations are discussed.
Processing of viral proteins for recognition by CTL involves degradation of the proteins in the cytosol of an infected cell followed by transport of the resulting peptides into the endoplasmic reticulum (ER) by the TAP1/2 complex. Uncertainty exists over the site of processing of viral envelope (env) proteins since the extracellular domains of env proteins are not present in the cytosol where the class I Ag-processing pathway begins. Rather, the ectodomains of env proteins are cotranslationally translocated into the ER during biosynthesis. To analyze env protein processing, we used the herpes simplex virus protein ICP47 to block peptide transport by TAP1/2 and examined the effects of TAP blockade on the processing of the HIV-1 env protein. For the majority of env-specific CD8+ CTL, the processing pathway required TAP1/2-mediated transport of cytosolic peptides into the ER. To determine how env peptides are generated in the cytosol, we analyzed the processing of two TAP1/2-dependent epitopes containing N-linked glycosylation sites. In each case, processing involved glycosylation-dependent posttranslational modification of asparagine residues to aspartic acid. These results are consistent with cotranslational translocation of env into the ER, where glycosylation occurs. This is followed by export of a fraction of the newly synthesized protein into the cytosol, where it is deglycosylated, with conversion of the asparagines to aspartic acid residues. Following cytoplasmic proteolysis, env peptides are retransported by TAP1/2 into the ER, where association with class I occurs. Thus, the env protein can enter the class I pathway through multiple distinct processing mechanisms.
BACKGROUND: This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation of metoprolol, metoprolol succinate (CR/XL). METHODS AND RESULTS: Sixty patients were randomly assigned with a 2:1 ratio, drug versus placebo, administered with a gradually increasing dose of 12.5 to 150 mg of blinded medication during an 8-week period and continued for 6 months. The average peak dose achieved was 99 mg and 132 mg in the metoprolol succinate and placebo groups, respectively. The drug was well tolerated and there was no significant difference in drug withdrawals, New York Heart Association class, or quality of life assessment. The increase in left ventricular ejection fraction measure at baseline and 6 months measured by radioisotopic ventriculography was greater in the metoprolol succinate group (27. 5% to 36.3%) than in the placebo group (26% to 27.9%) (P <.015). Examination of serial Holter electrocardiographic recordings indicate that metoprolol succinate therapy was associated with a significant (P <.05) decrease in total ventricular ectopy at 8 weeks of therapy and a decrease in ventricular couplets and nonsustained ventricular tachycardia at 8 through 26 weeks of therapy. No changes were observed in plasma norepinephrine during therapy except a transitory significant (P <.05) increase in N terminal proatrial natriuretic factor at 8 weeks in the metoprolol succinate group. CONCLUSIONS: This study indicates that treatment with metoprolol succinate for a 6-month period is safe and well tolerated and is associated with an increase in left ventricular ejection fraction and a decrease in ventricular ectopic beats.
AIMS: We investigated whether levels of N-terminal proatrial natriuretic peptide (N-terminal proANP) reflect the severity of coronary artery disease in chronic, stable angina pectoris. Furthermore, we investigated if revascularization by percutaneous transluminal coronary angioplasty (PTCA) affected the N-terminal proANP level and, finally, whether restenosis could be predicted by changes in N-terminal proANP after PTCA. METHODS AND RESULTS: N-terminal proANP was measured in 286 patients before and after PTCA. The patients' baseline level of N-terminal proANP (787+/-403 pmol/l) correlated significantly with left ventricular end diastolic pressure, age and serum creatinine, but not with the number of stenotic vessels. Twenty-four hours post-PTCA N-terminal proANP decreased significantly, and completely revascularized patients demonstrated a decline two-fold larger than those incompletely revascularized (deltaN-terminal proANP -114+/-178 vs. -53+/-231 pmol/l, P<0.05). After 14 days N-terminal proANP had returned to baseline in both groups. Changes in N-terminal proANP from post-PTCA to the final follow-up was not predictive of angiographic restenosis. INTERPRETATION: The significant decrease in N-terminal proANP observed after angioplasty, most pronounced in patients completely revascularized, is thought to reflect a transient improvement in resting left ventricular function.
We postulated previously that variables related to pulmonary flow are independent predictors of levels of atrial natriuretic peptide in children with congenital heart disease. The aim of this study was to test this hypothesis in relation to other hemodynamic and clinical variables. During catheterization we measured the levels of plasma N-terminal atrial natriuretic peptide prohormone in the plasma of 68 children with congenital heart disease. All had undergone complete clinical, echocardiographic and invasive hemodynamic investigations. The influence on the prohormone was analyzed for 10 different variables in a multiple linear regression model. The variability could be explained in large parts (adjusted R2 =77.2%) by variations in atrial pressures or sizes, together with the degree of excessive pulmonary blood flow and signs of heart failure. A value for atrial natriuretic peptide prohormone above 800 pmol/l predicted hemodynamic imbalance (defined as elevated pressures in left or right atrium or the pulmonary arteries, and/or Qp/Qs > 1.5) with a specificity of 94%, a sensitivity of 73%, a positive likelihood ratio of 12.2, and a negative likelihood ratio of 0.29. In conclusion, variables related to pulmonary blood flow are influential determinants of the levels of atrial natriureic peptide in children with congenital heart disease. Atrial pressures, and symptoms of heart failure are also of major importance.
AIMS: Cardiac peptides have diagnostic and prognostic value in heart failure. Their plasma concentrations, however, are sensitive to rapid changes in haemodynamics. As blood sampling under standard conditions is not feasible in clinical practice, it is important to know which peptides are most resistant to change. Therefore, the present study investigated the differences in response to exercise between atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, brain natriuretic peptide and the recently identified N-terminal probrain natriuretic peptide. METHODS AND RESULTS: Fifty-two patients with chronic heart failure performed a symptom-limited graded bicycle exercise. Blood samples for determination of plasma concentrations of cardiac peptides were drawn at rest and at peak exercise. There was a significant difference in percentage increase in response to exercise between the four peptides (P<0.0001). N-terminal proatrial natriuretic peptide increased less than atrial natriuretic peptide (5+/-18% vs 59+/-58%;P<0.0001). The difference in increase between N-terminal probrain natriuretic peptide and brain natriuretic peptide was less distinct but still significant (24+/-24% vs 38+/-52%, P<0.05). CONCLUSIONS: Both N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide increased less in response to exercise than their C-terminal counterparts. This implies that the circumstances under which blood sampling for measurements of N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide should be performed are more favourable than the blood sampling conditions for atrial natriuretic peptide and brain natriuretic peptide.
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Infection control measures in the health care setting should protect patients and staff from cross-infection. The prevention of harm is an essential part of good medical practice and failure might result in professional misconduct proceedings by the General Medical Council (GMC) and prosecution under the Health and Safety at Work legislation, as well as civil liability. For a health authority, overall responsibility for public health includes arrangements for the control of communicable diseases and infection in hospital and the community (NHS Management Executive, 1993), a function usually led by the Consultant in Communicable Disease Control (CCDC). This paper describes one district's collaborative approach between public health and GPs to assess and improve local infection control standards.
Approximately 15-20% of individuals infected with the human immunodeficiency virus will develop severe neurological disease. This may be due in part to virus-induced release of a number of putative neurotoxins. However, there is little information to predict which individuals will progress to dementia or the precise mechanisms that drive pathogenesis. In an effort to identify early markers of neurological disease progression we used an in vitro bioassay with rat cortical neurons to test for the presence of toxins in CSF from 40 HIV-infected humans with mild, minimal or no neurological disease. A subset of HIV-infected individuals was found to have significant toxic activity in CSF indicating that toxic factors may be circulating prior to the development of dementia. The toxicity was concentration dependent and due to a factor with a molecular mass of less than 30 kDa. Only a small proportion of the cell death appeared to be due to apoptosis. Neuronal toxicity was associated with a gradual accumulation of intracellular calcium in a subset of cortical neurons over a period of 1-2 h and in the absence of a significant acute response. Individuals with both high viral burden and high CSF toxicity were significantly more likely to have neurological symptoms. These initial analyses indicate that toxic factors are present in the CSF of HIV-infected patients that could serve as useful markers of neurological disease progression and provide insights into pathogenic mechanisms in vivo.
Registered Nurses wishing to re-enter the paid workforce have been shown to experience low self-esteem and high levels of anxiety. An intensive twelve-week re-entry program was designed to address these needs through a process of critical pedagogy. In this paper the student cohort since 1995 is described and the program, its structure, style, physical environment, teaching, and course content are introduced. Evaluation of student outcomes was ascertained by a convenience survey in which a questionnaire was posted to successful students. The results included employment rates of 97.4% and high levels of work and personal satisfaction. Both the benefits and the limitations of the program are discussed in light of the questionnaire responses.
Texas red-labeled hyaluronan (TR-HA) is rapidly taken up in a CD44 independent manner into ras-transformed 10T1/2 fibroblasts, where it accumulates in both cell ruffles/lamellae, the perinuclear area, and the nucleus. HA does not accumulate in the cell ruffles/lamellae of parental 10T1/2 cells. Addition of HA to ras-transformed cells promotes their random motility but has no effect on 10T1/2 cell motility. 10T1/2 cells can be modified to take up HA into cell ruffles by exposure to phorbol ester or direct microinjection of HA into cells. Both treatments significantly stimulate 10T1/2 cell motility.
The serine/threonine kinase p21-activated kinase (PAK) has been implicated as a downstream effector of the small GTPases Rac and Cdc42. While these GTPases evidently induce a variety of morphological changes, the role(s) of PAK remains elusive. Here we report that overexpression of betaPAK in PC12 cells induces a Rac phenotype, including cell spreading/membrane ruffling, and increased lamellipodia formation at growth cones and shafts of nerve growth factor-induced neurites. These effects are still observed in cells expressing kinase-negative or Rac/Cdc42 binding-deficient PAK mutants, indicating that kinase- and p21-binding domains are not involved. Furthermore, lamellipodia formation in all cell lines, including those expressing Rac binding-deficient PAK, is inhibited significantly by dominant-negative RacN17. Equal inhibition is achieved by blocking PAK interaction with the guanine nucleotide exchange factor PIX using a specific N-terminal PAK fragment. We conclude that PAK, via its N-terminal non-catalytic domain, acts upstream of Rac mediating lamellipodia formation through interaction with PIX.
Knowledge of the stage composition and the temporal dynamics of human cognitive operations is critical for building theories of higher mental activity. This information has been difficult to acquire, even with different combinations of techniques such as refined behavioral testing, electrical recording/interference, and metabolic imaging studies. Verbal object comprehension was studied herein in a single individual, by using three tasks (object naming, auditory word comprehension, and visual word comprehension), two languages (English and Farsi), and four techniques (stimulus manipulation, direct cortical electrical interference, electrocorticography, and a variation of the technique of direct cortical electrical interference to produce time-delimited effects, called timeslicing), in a subject in whom indwelling subdural electrode arrays had been placed for clinical purposes. Electrical interference at a pair of electrodes on the left lateral occipitotemporal gyrus interfered with naming in both languages and with comprehension in the language tested (English). The naming and comprehension deficit resulted from interference with processing of verbal object meaning. Electrocorticography indices of cortical activation at this site during naming started 250-300 msec after visual stimulus presentation. By using the timeslicing technique, which varies the onset of electrical interference relative to the behavioral task, we found that completion of processing for verbal object meaning varied from 450 to 750 msec after current onset. This variability was found to be a function of the subject's familiarity with the objects.
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An APTT-based kit method (Coatest APC Resistance), modified by predilution 1+4 of sample plasma in a plasma diluent containing a heparin antagonist (V-DEF plasma), has been evaluated on plasmas from patients treated with unfractionated (n = 110) or either of three different low molecular heparins (n=44), or with oral anticoagulants (n=147). Irrespective of treatment, no difference was observed in the APC response as compared to untreated individuals (n=62), and a complete discrimination was obtained between individuals with a normal factor V genotype and those carrying the FV:Q506 mutation. Furthermore, in contrast to the original, APTT-based kit method, where anticoagulant therapy results in a prolongation of the APTT, the modified kit provided APTT values within the normal range for orally anticoagulated (INR< or =6) and for all heparin treated (< or =1 IU/mL) patients except for one with a suspected presence of phospholipid antibodies. Due to the predilution in V-DEF plasma, contamination with platelets up to 1.5 x 10(4)/microL had a negligible effect on analysis of frozen plasmas regarding their classification as normal or abnormal. Analyses of fresh plasmas show no influence at platelet counts up to 6x10(4)/microL. Consequently, negligible differences in APC ratios were obtained between fresh and frozen plasmas. In conclusion, the modified kit method is applicable to plasmas from anticoagulated patients as well as from untreated individuals, allowing a safe assignment regarding the presence or absence of the FV:Q506 genotype.