Epidural analgesia for labour and delivery: informed consent issues.
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Analgesia, Epidural↗
Biomedical subjects
A Clark
Publications and source records attributed to A Clark.
Prevention and early intervention for depression in adolescence and early adult life.
Over the past decade there has been increasing interest in the possibility that early intervention might prevent mental disorders later in life. Indeed, in the United Kingdom the Department of Health recommends that health promotion should be one of the main functions of child mental health services, a suggestion that has been endorsed by professional bodies. It is easy to see why both purchasers and providers of mental health services would be interested in prevention, but will preventive interventions work in practice? This paper discusses the possibility of preventing depressive disorder in late adolescence and early adult life by intervening in childhood and early adolescence. The paper begins with a description of the phenomenology of depression and its risk factors. It then goes on to describe a framework of prevention and within this framework explores whether there is an adequate knowledge base. The general perspective that is presented is one of cautious scepticism. It is argued that difficulties in defining depression and identifying risk factors that can easily be remedied make it unlikely that within the foreseeable future primary prevention programmes will prove to be more effective than treatment and rehabilitation of affected individuals. The possibility that preventive programmes could do harm will also be discussed. The paper concludes with some proposals about appropriate targets for prevention. It is suggested that apart from a few policy areas where there are some relatively harmless measures that could protect from later depression, a balanced preventive programme will give higher priority to treatment services than to those concerned with early intervention.
Adolescent↗
Fibrillar islet amyloid polypeptide (amylin) is internalised by macrophages but resists proteolytic degradation.
Pancreatic islet amyloid, formed from islet amyloid polypeptide, is found in 96% of Type II (non-insulin-dependent) diabetic patients. Islet amyloidosis is progressive and apparently irreversible. Fibrils immunoreactive for islet amyloid polypeptide are found in macrophages associated with amyloid, suggesting that deposits can be phagocytosed. To determine the mechanism for the recognition and internalisation of fibrils, mouse peritoneal macrophages were cultured with fibrillar synthetic human islet amyloid polypeptide. Fibrils did not exert a cytotoxic effect over 72 h of culture. The uptake and degradation of fibrils was analysed by quantitative light-and electron-microscopic immunocytochemistry and immunoreactivity was detectable in 86+/-3% cells within 6 h of culture. Neither polyinosinic acid (200 microg/ml) nor nocodazole (10 microg/ml) inhibited fibril uptake, suggesting that internalisation is not blocked by poly-ions and is independent of microtubule assembly. Inhibition of pseudopodia formation by cytochalasin B blocked fibriI uptake. Fibril aggregates became condensed in lysosomes to form protofilaments and were resistant to intracellular proteolysis. Fibrils can be phagocytosed by macrophages in vitro but amyloid-associated factors may block the recognition of fibrils in vivo preventing the removal of islet amyloid in diabetes.
Amyloid↗
The influence of epidural analgesia on cesarean delivery rates: a randomized, prospective clinical trial.
OBJECTIVE: The effects of epidural analgesia on the progress of labor are controversial. The objective of this study was to determine the effect of epidural analgesia on cesarean delivery rates in a population of patients randomly assigned to receive either epidural analgesia or intravenous opioids for intrapartum pain relief. STUDY DESIGN: From January 1995 to May 1996, 318 spontaneously laboring, term, nulliparous patients were randomly assigned to receive either intravenous opioids or epidural analgesia for pain relief. Labor was managed according to the principles of active management of labor. Cesarean delivery was performed for obstetric indications. Data analysis was conducted on an intent-to-treat basis. A subanalysis was subsequently performed on patients who were compliant with the allocated form of treatment. RESULTS: One hundred sixty-two patients were randomly assigned to receive intravenous meperidine and 156 were randomly assigned to receive epidural analgesia. Maternal age, gravidity, race, gestational age, and cervical dilatation at admission and at first analgesic dose did not differ between the groups. Intent-to-treat data analysis revealed no significant difference in the cesarean delivery rate between the 2 groups, being 13.6% in the opioid group and 9.6% in the epidural group (relative risk 0.70, 95% confidence interval 0.38-1.31, P >.05). Cesarean delivery rates for the indication of dystocia also did not differ, being 10.5% in the opioid group and 5.8% in the epidural group (relative risk 0.56, 95% confidence interval 0.26-1.21, P >.05). Subanalysis of the data from patients who were compliant with the allocated form of treatment revealed that patients in the epidural group (n = 147) were 3 times more likely to have an active phase duration >/=8 hours and were 10 times more likely to require >/=2 hours in the second stage of labor than were those in the opioid group (n = 78). There were no significant differences in cesarean delivery rates in this subanalysis, being 7.7% in the opioid group and 8.8% in the epidural group (relative risk 1.15, 95% confidence interval 0.45-2.91, P >. 05). The cesarean delivery rates for dystocia were also similar in the subanalysis, being 3.8% in the opioid group and 5.5% in the epidural group (relative risk 1.42, 95% confidence interval 0.39-5. 22, P >.05). CONCLUSION: Epidural analgesia provides safe and effective intrapartum pain control and may be administered without undesirable effects on labor outcome.
Adolescent↗
Islet amyloid polypeptide decreases the effects of insulin-like growth factor-I on glucose transport and glycogen synthesis in skeletal muscle.
Previous studies have shown that islet amyloid polypeptide (IAPP) is co-secreted with insulin from the beta-cell. IAPP reduces insulin-stimulated rates of glycogen synthesis in skeletal muscle but the mechanisms are unclear. Insulin-like growth factor I (IGF-I) is an important regulator of glucose metabolism in skeletal muscle and acts through its own receptor, which has many structural and functional similarities with the insulin receptor. Despite this, the effects of IGF-I on glucose utilization are not identical to those of insulin. The aim of the study was to determine the effects of IAPP on IGF-I-stimulated rates of glucose transport and metabolism (measured by 3-O-methyl[3H]glucose and [U-14C]glucose, respectively) in rat soleus muscle, and compare them with those simulated by insulin. IAPP (10 nM) decreased the sensitivity of 3-O-methylglucose transport, the flux of glucose to hexosemonophosphate and the sensitivity of glycogen synthesis to IGF-I. In contrast, IAPP had no effect on IGF-I-stimulated rates of lactate formation (i.e., glycolysis). IAPP decreased the sensitivity of 3-O-methylglucose transport and glycogen synthesis to insulin. It is concluded that IAPP blunts the stimulation of glucose uptake and deposition by IGF-I or insulin in skeletal muscle. These observations expand those made initially for IAPP and insulin and suggest that IAPP affects IGF-I- or insulin-stimulated glucose metabolism in muscle by a mechanism which is common for both hormones. These experiments may serve as a framework for future studies in order to clarify the mechanisms by which IAPP affects glucose metabolism in skeletal muscle.
Amyloid↗
Is blood pressure related to kidney size and shape?
OBJECTIVE: To examine the relationship between blood pressure and the size and shape of the kidneys in healthy volunteers from the community. DESIGN: A cross-sectional community-based study of normal volunteers in Portsmouth City, Hampshire, UK. SUBJECTS: Subjects numbered 185 (99 female), aged 19-66 years. RESULTS: Blood pressure was higher in men, and in those with higher body mass index. Both systolic and diastolic blood pressure were correlated with the derived kidney volume. However, when corrected for age, sex and BMI the relationship was not statistically significant. Blood pressure correlated inversely with the width : length ratio of the left kidney. CONCLUSIONS: Blood pressure was not correlated with kidney size in this group of adults.
Adult↗
Comparative phenotypic characteristics of Staphylococcus aureus isolates from line and non-line associated septicaemia, CAPD peritonitis, bone/joint infections and healthy nasal carriers.
This study compared specific phenotypic and potential virulence characteristics of Staphylococcus aureus isolates from invasive infections and nasal carriers. Three hundred and sixty isolates were studied; 154 from septicaemia (69 line associated, 85 non-line), 79 from continuous ambulatory peritoneal dialysis (CAPD) peritonitis, 64 from bone/joint infections and 64 from healthy nasal carriers. The isolates were tested for production of enterotoxins (SE) A, B, C or E, toxic shock syndrome toxin-1 (TSST-1) protein A, and also for lipolytic, proteolytic, fibrinolytic and haemolytic activities. In addition phage typing, crystal violet reaction, urease and galactose breakdown were studied. Seventy-one percent of isolates were enterotoxigenic. Production of SEA was significantly lower amongst the bone/joint isolates. Production of SEB, was lower among the control group compared with CAPD, bone/joint, and non-line septicaemia isolates. SEE production was higher among the bone/joint isolates compared with the CAPD and non-line septicaemias and production of TSST-1 was significantly higher among nasal isolates compared with isolates causing infection. Almost all of the isolates were lipolytic, with highest activity amongst nasal and bone/joint isolates. Fibrinolytic activity was similar in the five groups of isolates. Proteolytic activity ranged from 35 to 62% of isolates with the lowest frequency among septicaemia isolates. In all, 80-90% of isolates were haemolytic, although CAPD isolates were less likely to be haemolytic. Isolates from the control and CAPD group more frequently belonged to phage group I. TSST-1 does not appear to be an important requirement for invasive infections, but SEB may be. Proteolysis and intensity of lipolysis appear to be less important in septicaemia, and haemolysis may not be important in CAPD peritonitis.
Bacterial Toxins↗
Molecular characterization of the alpha-glucosidase gene (malA) from the hyperthermophilic archaeon Sulfolobus solfataricus.
Acidic hot springs are colonized by a diversity of hyperthermophilic organisms requiring extremes of temperature and pH for growth. To clarify how carbohydrates are consumed in such locations, the structural gene (malA) encoding the major soluble alpha-glucosidase (maltase) and flanking sequences from Sulfolobus solfataricus were cloned and characterized. This is the first report of an alpha-glucosidase gene from the archaeal domain. malA is 2,083 bp and encodes a protein of 693 amino acids with a calculated mass of 80.5 kDa. It is flanked on the 5' side by an unusual 1-kb intergenic region. Northern blot analysis of the malA region identified transcripts for malA and an upstream open reading frame located 5' to the 1-kb intergenic region. The malA transcription start site was located by primer extension analysis to a guanine residue 8 bp 5' of the malA start codon. Gel mobility shift analysis of the malA promoter region suggests that sequences 3' to position -33, including a consensus archaeal TATA box, play an essential role in malA expression. malA homologs were detected by Southern blot analysis in other S. solfataricus strains and in Sulfolobus shibatae, while no homologs were evident in Sulfolobus acidocaldarius, lending further support to the proposed revision of the genus Sulfolobus. Phylogenetic analyses indicate that the closest S. solfataricus alpha-glucosidase homologs are of mammalian origin. Characterization of the recombinant enzyme purified from Escherichia coli revealed differences from the natural enzyme in thermostability and electrophoretic behavior. Glycogen is a substrate for the recombinant enzyme. Unlike maltose hydrolysis, glycogen hydrolysis is optimal at the intracellular pH of the organism. These results indicate a unique role for the S. solfataricus alpha-glucosidase in carbohydrate metabolism.
Amino Acid Sequence↗
Amelioration of diabetes in nonobese diabetic mice with advanced disease by linomide-induced immunoregulation combined with Reg protein treatment.
Oral linomide, (quinoline-3-carboxamide), has been shown to prevent autoimmune insulitis, islet destruction, and diabetes in NOD mice treated at an early stage of the disease, but confers only partial protection in animals with advanced disease. Reg protein, the gene product of a complementary DNA isolated from a regenerating rat islet library, has been previously shown to induce expansion of beta-cell mass in pancreatectomized rats. To determine the effect of treatment combining immunomodulation and Reg protein on advanced autoimmune diabetes, we treated female NOD mice with oral linomide and i.p. Reg protein injections. In 14-week-old animals with less severe disease (glucose tolerant), treatment with each agent alone resulted in amelioration of diabetes, as did treatment with Reg alone in 5-week-old prediabetic mice. In 14-week-old animals with more severe disease (glucose intolerant), only treatment with the combination of both agents, but not that with each separately, resulted in amelioration of diabetes. Our study suggests that treatment aimed at abrogation of autoimmunity combined with expansion of beta-cell mass constitutes a potential therapeutic approach for treatment of insulin-dependent diabetes mellitus.
Adjuvants, Immunologic↗
A pilot study of computer-aided vicarious exposure for obsessive-compulsive disorder.
OBJECTIVE: This study reports the use of an interactive computer program to instruct vicarious exposure and ritual prevention for obsessive-compulsive disorder (OCD). METHOD: Thirteen OCD volunteers and 10 non-OCD volunteers completed three 45-minute sessions at weekly intervals. Subjects with OCD completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Padua Inventory (PI) and the Beck Depression Inventory (BDI) 1 week prior to and 1 week after the three computer treatment sessions. Non-OCD subjects only completed these measures at baseline, allowing confirmation that they had no significant level of OCD symptomatology. RESULTS: In the OCD subjects, scores fell significantly on the PI and BDI, and Y-BOCS scores fell non-significantly. Engagement in vicarious exposure with ritual prevention improved from sessions 1-3. Compared to the non-OCD participants, OCD subjects did less vicarious exposure in session 1 but not sessions 2 and 3. Performance of vicarious exposure by OCD subjects in session 1 correlated with pre-post improvement in PI and BDI scores. CONCLUSIONS: The vicarious exposure program may have a role to play as an adjunct in behaviour therapy.
Adolescent↗
Macrophages and pancreatic islet amyloidosis.
Islet amyloid formed from islet amyloid polypeptide (IAPP, amylin) is found in spontaneously diabetic monkeys and cats. Islet amyloidosis is progressive, apparently irreversible and is associated with destruction of insulin-secreting cells. The role of macrophages in the destruction and removal of islet amyloid is unknown. Therefore, the presence and morphology of macrophages were determined by electron and quantitative light microscopy in islets of diabetic and nondiabetic man and monkeys and in transgenic mice expressing the gene for human IAPP. Tissue macrophages were present in all pancreatic sections and tissue distribution was similar in exocrine and endocrine areas. There was no difference in macrophage density in amyloidotic and amyloid-free islets in monkeys and man. Macrophage density was similar in islets of transgenic mice expressing human IAPP which do not contain amyloid in vivo but in which fibrils are formed in vitro following islet isolation compared to islets from mice expressing rat IAPP which is not amyloidogenic. IAPP amyloid fibrils were visible by electron microscopy in lysosomes of pancreatic macrophages in man, monkeys and human IAPP transgenic mice. Thus, human IAPP is internalised but inefficiently degraded by tissue macrophages. Diabetes-associated amyloidosis is not associated with visible recruitment of macrophages for removal of amyloid or islet debris.
Aged↗
Different patterns of variation at the X- and Y-chromosome-linked microsatellite loci DXYS156X and DXYS156Y in human populations.
We compared the global pattern of variation at two homologous microsatellites mapping to the long arm of the X chromosome (DXYS156X) and to the short arm of the Y chromosome (DXYS156Y) in humans. A single pair of oligonucleotide primers amplifies these two nonallelic loci, each of which contains polymorphism in the number of pentanucleotide units. We observed 11 alleles in a sample of 2290 X chromosomes and 2006 Y chromosomes from 50 populations representing 6 major geographic regions. The overlapping size range of the X- and Y-chromosome alleles indicated a more complex distribution of alleles at these two loci than previously reported. Contrasting patterns of X-chromosome-linked and Y-chromosome-linked variation were reflected in statistically significant differences in genetic diversity values among geographic regions and between X and Y chromosomes. Higher levels of diversity characterized the DXYS156X locus in Africa (0.799 +/- 0.004) and the DXYS156Y locus in East Asia (0.700 +/- 0.006) compared with populations from other regions. These different patterns of variation can be explained by a combination of processes at both the molecular and population levels, including variable mutation rates, different effective population sizes, and genetic drift.
Algorithms↗
A community outbreak of Vero cytotoxin producing Escherichia coli O157 infection linked to a small farm dairy.
A community outbreak of infection with Vero cytotoxin producing Escherichia coli O157 (VTEC 0157) occurred in a small area of north west England in 1996. An outbreak control team was established to investigate the outbreak and implement control measures. Nine people developed symptomatic infections with VTEC O157, and a further three were found to be excreting the bacteria. All were infected with the same genotype of VTEC O157. Three children under 5 years of age and one adult were admitted to hospital. One child developed haemolytic uraemic syndrome. All cases recovered. All primary cases had consumed milk from a particular farm dairy. No other common foods were identified. The farm dairy had a faulty pasteuriser and the potential for post pasteurisation contamination existed. VTEC O157 was isolated from a milk sock specimen and from two cows, but these strains differed from that infecting the cases. All local doctors and the public were alerted and advised about preventative measures. Distribution of unpasteurised milk from the farm was discontinued as was the sale of pasteurised milk when the faulty pasteuriser was discovered. A replacement pasteuriser was installed and checked before milk was released for human consumption. No conclusive evidence of the origin of this outbreak was found, but the farm was the most probable source. The investigations raised concerns about the distribution of VTEC O157 colonised dairy cattle, the natural history of such colonisation, the effectiveness of pasteurisation with respect to the elimination of VTEC O157, and the effectiveness of current legislation for the prevention and control of milkborne infection.
Adult↗
Relationship between isokinetic muscle strength and exercise capacity in chronic heart failure.
The exercise intolerance and excessive ventilatory response to exercise of chronic heart failure is associated with abnormalities of skeletal muscle function, in particular a reduction in muscle strength. Isometric and isokinetic leg muscle strength were measured in 10 patients with chronic heart failure and 10 age-matched controls. Each subject undertook maximal exercise testing to measure peak oxygen consumption (V(O2)) and the ventilatory response to exercise as measured by the slope of the relation between ventilation and carbon dioxide production (V(E)/V(CO2) slope). Quadriceps strength (mean (S.D.)) was reduced in heart failure as measured by isometric (444.9 (129.6) N vs. 556.0 (136.0); P<0.01) and isokinetic (123.6 (30.2) Nm vs. 146.8 (40.0); P=0.04). Hamstring strength was also reduced as measured by isokinetic testing (53.6 (15.6) Nm vs. 71.1 (28.1); P=0.02). Isokinetic and isometric strengths correlated, but not closely (r=0.52, P<0.001). There were negative correlations between the V(E)/V(CO2) slope, and isokinetic measures: with average torque, r=-0.62, P<0.004; with peak torque, r=-0.64, P=0.002. We have found evidence for reduced muscle function affecting both knee flexors and extensors. This reduction in muscle strength correlates with the ventilatory response to exercise. These observations lend support to the muscle hypothesis of the generation of symptoms in chronic heart failure.
Angiotensin-Converting Enzyme Inhibitors↗
Curvaceous model of recovery from depression.
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Antidepressive Agents↗
Transvaginal electrical stimulation for female urinary incontinence.
OBJECTIVE: Our purpose was to determine the objective and subjective efficacy of transvaginal electrical stimulation for treatment of common forms of urinary incontinence in women. STUDY DESIGN: A prospective, double-blind, randomized clinical trial included 121 women with either urinary incontinence caused by detrusor instability or genuine stress incontinence, or both (mixed incontinence). Participants used the assigned device for 8 weeks. Identical preintervention and postintervention assessment included multichannel urodynamic testing, quality-of-life scale, and urinary diaries. RESULTS: A total of 121 women completed this study at four North American urogynecology centers. Detrusor instability was cured (stable on provocative cystometry) in 49% of women with detrusor instability who used an active electrical device (p = 0.0004, McNemar's test), whereas there was no statistically significant change in the percentage with detrusor instability in the sham device group. There was no statistically significant difference between the preintervention and postintervention rates of genuine stress incontinence for either the active device group or the sham device group. CONCLUSION: This form of transvaginal electrical stimulation may be effective for treatment of detrusor overactivity, with or without genuine stress incontinence.
Adult↗
Onset of action, efficacy, and safety of a single dose of fexofenadine hydrochloride for ragweed allergy using an environmental exposure unit.
BACKGROUND: Fexofenadine hydrochloride is the active acid metabolite of terfenadine. Fexofenadine's anti-allergic properties require confirmation in a clinical setting. OBJECTIVE: The purpose of this study was to characterize the time to onset of clinically important relief of symptoms of allergic rhinitis in subjects taking single doses of either 60 mg or 120 mg fexofenadine HCl, or placebo, after exposure to ragweed pollen in a controlled environment. Other objectives were to assess the efficacy and safety of single doses of fexofenadine HCl. METHODS: One hundred forty-six ragweed-sensitive subjects were primed in the off-season with ragweed pollen in the environmental exposure unit. One hundred thirty-six subjects who adequately responded to priming entered a single-dose placebo phase. Placebo-responders were disqualified from the study, leaving 99 subjects with adequate symptoms to be randomized and given a single dose of either fexofenadine HCl 120 mg (33), 60 mg (33) or placebo (33), after 60 minutes of allergen exposure. Exposure continued over five hours and subjects recorded symptoms every 20 minutes. This study was of a randomized, placebo-controlled, double-blind, parallel design. RESULTS: Median time to onset for relaxed criteria clinically important relief was 60 minutes for both fexofenadine treatment groups, and 100 minutes for placebo (P = .018). The proportion with relief was 82% at 60 mg, 85% at 120 mg, and 64% for placebo. Treated groups had reductions in symptom scores double that of placebo. CONCLUSIONS: Fexofenadine is safe and efficacious at single doses of 60 mg and 120 mg. Average time to onset was 60 minutes using controlled pollen exposure in an environmental exposure unit.
Adolescent↗
Trading spaces: computation, representation, and the limits of uninformed learning.
Some regularities enjoy only an attenuated existence in a body of training data. These are regularities whose statistical visibility depends on some systematic recoding of the data. The space of possible recoding is, however, infinitely large--it is the space of applicable Turing machines. As a result, mappings that pivot on such attenuated regularities cannot, in general, be found by brute-force search. The class of problems that present such mappings we call the class of "type-2 problems." Type-1 problems, by contrast, present tractable problems of search insofar as the relevant regularities can be found by sampling the input data as originally coded. Type-2 problems, we suggest, present neither rare nor pathological cases. They are rife in biologically realistic settings and in domains ranging from simple animat (simulated animal or autonomous robot) behaviors to language acquisition. Not only are such problems rife--they are standardly solved! This presents a puzzle. How, given the statistical intractability of these type-2 cases, does nature turn the trick? One answer, which we do not pursue, is to suppose that evolution gifts us with exactly the right set of recording biases so as to reduce specific type-2 problems to (tractable) type-1 mappings. Such a heavy-duty nativism is no doubt sometimes plausible. But we believe there are other, more general mechanisms also at work. Such mechanisms provide general (not task-specific) strategies for managing problems of type-2 complexity. Several such mechanisms are investigated. At the heart of each is a fundamental poly--namely, the maximal exploitation of states of representation already achieved by prior, simpler (type-1) learning so as to reduce the amount of subsequent computational search. Such exploitation both characterizes and helps make unitary sense of a diverse range of mechanisms. These include simple incremental learning (Elman 1993), modular connectionism (Jacobs et al. 1991), and the developmental hypothesis of "representational redescription" (Karmiloff-Smith 1979; 1992). In addition, the most distinctive features of human cognition--language and culture--may themselves be viewed as adaptations enabling this representation/computation trade-off to be pursued on an even grander scale.
Humans↗