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Biomedical subjects

J Harris

Publications and source records attributed to J Harris.

At least 37 records · Page 2Linked to original sources
PubMed2001

Adaptive changes in withdrawal reflexes after noxious stimulation at the heel and the toes in the decerebrated rabbit.

In decerebrated rabbits, reflexes evoked by electrical stimulation of the toes in the ankle flexor tibialis anterior were enhanced for > 30 min after application of 20% mustard oil to the base of the toes, whereas responses of the ankle extensor medial gastrocnemius to stimulation of the heel were depressed for > 20 min by the same stimulus. Applied to the heel, mustard oil had inconsistent effects on the flexor reflex but potentiated the extensor response for approximately 1 h. Intrathecal co-administration of naloxone (25 microg) with the selective alpha(2)-adrenoceptor antagonist RX 821002 (200 microg) enhanced both reflexes to more than twice pre-drug values and reduced or abolished all effects of mustard oil. These data confirm that the location of a noxious stimulus is an important determinant of the subsequent adaptive changes in reflexes, and indicate roles for endogenous opioids and noradrenaline in these processes.

Adaptation, Physiological↗
PubMed2001

Effect of the APOE promoter polymorphisms on cerebral amyloid peptide deposition in Alzheimer's disease.

Polymorphisms in the promoter region of the apolipoprotein E gene (APOE) affect the amount of amyloid peptide (Abeta) in the brains of patients with Alzheimer's disease. We measured Abeta load immunohistochemically in regions 8 and 9 of Brodman's area in 74 people with Alzheimer's disease. The amount of Abeta deposition was independent of APOE genotype in our cohort. These findings in patients with confirmed Alzheimer's disease are consistent with the hypothesis that variation in APOE expression directly affects Alzheimer's disease pathology.

Aged↗
PubMed2001

Cannabinoidergic and opioidergic inhibition of spinal reflexes in the decerebrated, spinalized rabbit.

The present experiments were designed to investigate the role(s) of cannabinoid receptors in modulating transmission in the sural-medial gastrocnemius withdrawal reflex of the decerebrated, spinalized rabbit and how, if present, cannabinoid-mediated control might interact with opioid-mediated inhibitions known to impinge on this reflex pathway. The selective CB(1) receptor antagonist SR 141716A enhanced reflexes by a factor of two after a cumulative dose of 100 nmol kg(-1) i.v., but had no effect on the endogenous opioid-mediated inhibition generated by repetitive electrical stimulation of the common peroneal nerve, or on the suppression of reflexes caused by i.v. administration of the synthetic opioid fentanyl. Given at a dose of 10 nmol kg(-1) i.v., the potent, CB(1)--CB(2) cannabinoid receptor agonist HU 210 inhibited medial gastrocnemius reflexes to approximately 30% of controls and significantly decreased both heart rate and blood pressure, but did not alter the inhibition of reflexes resulting from common peroneal nerve stimulation or i.v. fentanyl. The effects of HU 210 were reversed by SR 141716A. HU 210 was just as effective in inhibiting reflexes in the presence of the opioid antagonist naloxone (5 micromol kg(-1)) as it was in untreated animals. The data show that cannabinoids, acting through CB(1) receptors, are inhibitory in rabbit spinal cord and that there appears to be some endogenous cannabinoid tone under the conditions of the present experiments. The evidence of this study is that the inhibitory effects of opioids and cannabinoids in rabbit spinal cord are completely independent of each other, and are additive rather than synergistic.

Animals↗
PubMed2001

The risk of acquiring hepatitis B or C among public safety workers: a systematic review.

CONTEXT: Determination of the occupational risk of hepatitis B and C to public safety workers is important in identifying prevention opportunities and has significant legal and policy implications. OBJECTIVES: Characterize the risk of occupationally acquired infection: (1) risk of exposure to blood and body fluids, (2) seroprevalence of hepatitis B and C in the source population, and (3) risk of infection after exposure. DATA SOURCES: Electronic search of MEDLINE (1991-1999), HealthStar (1982-1999), and CINAHL (1975-1999) supplemented by selected reference citations and correspondence with authors of relevant articles. STUDY SELECTION: Peer-reviewed journal articles (N=702) that addressed the transmission of hepatitis B and C in law enforcement, correctional, fire, emergency medical services, and healthcare personnel were identified. One hundred five (15.0%) articles were selected for full-text retrieval; 72 (68.6%) were selected for inclusion. DATA ABSTRACTION: Articles selected for inclusion were abstracted by two reviewers and checked by a third reviewer, using a standard reporting form. DATA SYNTHESIS: Evidence tables were constructed, using the standardized abstracts. The tables were designed to summarize data for the key elements of the risk analysis. CONCLUSIONS: Data suggest that emergency medical service (EMS) providers are at increased risk of contracting hepatitis B, but data have failed to show an increased prevalence of hepatitis C. EMS providers have exposure risks similar to those of hospital-based healthcare workers. Other public safety workers appear to have lower rates of exposure. Urban areas have much higher prevalence of disease, and public safety workers in those areas are likely to experience a higher incidence of exposure events.

Blood-Borne Pathogens↗
PubMed2001

Ignorance, information and autonomy.

People have a powerful interest in genetic privacy and its associated claim to ignorance, and some equally powerful desires to be shielded from disturbing information are often voiced. We argue, however, that there is no such thing as a right to remain in ignorance, where a fight is understood as an entitlement that trumps competing claims. This does not of course mean that information must always be forced upon unwilling recipients, only that there is no prima facie entitlement to be protected from true or honest information about oneself. Any claims to be shielded from information about the self must compete on equal terms with claims based in the rights and interests of others. In balancing the weight and importance of rival considerations about giving or withholding information, if rights claims have any place, rights are more likely to be defensible on the side of honest communication of information rather than in defence of ignorance. The right to free speech and the right to decline to accept responsibility to take decisions for others imposed by those others seem to us more plausible candidates for fully fledged rights in this field than any purported right to ignorance. Finally, and most importantly, if the right to autonomy is invoked, a proper understanding of the distinction between claims to liberty and claims to autonomy show that the principle of autonomy, as it is understood in contemporary social ethics and English law, supports the giving rather than the withholding of information in most circumstances.

Confidentiality↗
PubMed2001

Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.

Amino Acid Sequence↗
PubMed2001

Maternal atopy and parity.

BACKGROUND: Family size and high birth order were related to the prevalence of hayfever and positive skin prick test. However, this association may be explained by maternal atopy. We examined the relationship between maternal atopy and the number of offspring in three European cohorts of pregnant women. METHODS: The mothers and their children (n = 1487) were recruited for the Asthma Multi-centre Infants Cohort Study (AMICS). The three concurrent cohorts (Ashford, Kent (UK); Menorca island (Spain) and Barcelona city (Spain) followed the same research protocol. Maternal and paternal atopy was identified by skin prick tests at different times at the three centres. RESULTS: Maternal atopy was inversely related to the number of offspring, an association which occurred in each of the three cohorts and remained when atopy was defined separately for individual allergens (a positive response to testing with either Der p 1 or grass pollen) and which was not confounded by maternal age, smoking nor social class (the adjusted odds ratios were 0.71, 0.79 and 0.26 for increasing number of offspring, P = 0.002). Neither maternal asthma (P = 0.43) nor paternal atopy (P = 0.58) were associated with the number of offspring. Maternal atopy was not related to reproductive outcomes. CONCLUSIONS: The association between maternal atopy and parity challenges the role of family size on child atopy, which should be studied in other populations.

Adult↗
PubMed2001

Crete: does farming explain urban and rural differences in atopy?

BACKGROUND: Urban-rural differences in the prevalence of atopy and associated allergic diseases have been reported in several non-European countries. Within Europe, where such variations are less striking, a farm childhood has been postulated to be protective. OBJECTIVE: We aimed to compare the prevalence of atopy in urban and rural children living in Crete and to examine the role of early exposure to a farming environment in explaining any measured differences. METHODS: A cross-sectional survey of children attending secondary schools in Iraklion, the capital city, and five villages 100 km to the south. Atopy was determined by the responses to skin prick tests with seven common aeroallergens. RESULTS: Nine-hundred and ninety-seven children participated in the survey. 19.6% of those living in Iraklion, but only 9.6% of those from the villages, had a positive response to one or more skin prick tests. Among urban children there were significant gradients in the prevalence of atopy across several categories of animal contact and consumption of farm (unpasteurized) milk products--before the age of 5 years. These differences, however, were not apparent among the rural children.

Adolescent↗
PubMed2001

The spatial organization of central sensitization of hind limb flexor reflexes in the decerebrated, spinalized rabbit.

This study was designed to investigate the relationship between the location of a noxious stimulus and the magnitude and duration of the plastic effects induced by that stimulus in withdrawal reflexes acting about the knee and the ankle, in rabbits. Reflexes were evoked in the nerves to the anterior tibial and semitendinosus flexor muscles by electrical stimulation at the toes. Repetitive, high intensity electrical stimulation of nerve trunks (sural, medial gastrocnemius, superficial peroneal, tibial, 100 pulses, 20 V, 1 ms at 0.5 Hz) was generally found to be a poor method for inducing central sensitization in these flexor reflexes. 'Natural' noxious stimulation induced more reliable enhancement of both reflexes. Mechanical (clamp) or chemical (mustard oil) stimulation of the heel induced prolonged (median duration >30 min) increases in reflexes to both muscles. Mechanical (clamp and superficial pinch) or chemical (mustard oil) stimulation of the toes, and injection of bradykinin into the gastrocnemius muscles or into the soft tissues of the sole of the foot, also led to enhancement of both reflexes, with the median duration of potentiation between 7 and 30 min. The effects obtained from deep tissue stimulation were generally weaker than those obtained after stimulation of superficial structures. These data show that there were no major differences in the effects obtained from the heel vs the toes, or between the two reflexes. It appears that the spatial organization of the spinal mechanisms underlying central sensitization of flexor withdrawal reflexes is rather more crudely drawn than that pertaining to the reflexes themselves. Furthermore, the data indicate that in the present preparation, afferents from deep tissues are no more effective in generating central sensitization than those from superficial structures.

Afferent Pathways↗
PubMed2001

Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study.

BACKGROUND: Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use. METHODS: Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment. RESULTS: Mean QTc among patients taking the drug was 408+/-18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2+/-20 ms. CONCLUSIONS: In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.

Arrhythmias, Cardiac↗
PubMed2001

Electrogastrographic norms in children: toward the development of standard methods, reproducible results, and reliable normative data.

BACKGROUND: Surface electrogastrography (EGG) is a noninvasive technique that detects gastric myoelectrical electric activity, principally the underlying pacemaker activity generated by the specialized interstitial cells of Cajal. Interest in the use of this methodology has grown because of its potential applications in describing functional gastrointestinal disorders, particularly as a tool in the evaluation of nausea, anorexia, and other dyspeptic symptoms. METHODS: Fifty-five healthy volunteers (27 female), ranging in age from 6 to 18 years (mean, 11.7 years), were studied for a 1-hour baseline preprandial period and a 1-hour postprandial period after consumption of a standard 448-kcal meal. Recordings were obtained with an EGG Digitrapper or modified Polygraph (Medtronic-Synectics, Shoreview, MN). Spectral analysis by an autoregressive moving average method was used to extract numerical data on the power and frequency of gastric electrical activity from the EGG signal. RESULTS: The authors present normative data for healthy children and adolescents studied under a standardized protocol. Mean dominant frequency was found to be 2.9 +/- 0.40 cycles per minute preprandially and 3.1 +/- 0.35 postprandially, with 80% +/- 13% of test time spent in the normogastric range (2-4 cycles per minute) before and 85% +/- 11% after the test meal. The response of several key parameters to meal consumption was considered, and the effects of age, gender, and body mass index (BMI) on the EGG were sought. CONCLUSIONS: There is a postprandial increase in the rhythmicity and amplitude of gastric slow waves, as other investigators have shown in adults. Key normative values are not dependent on age, gender, or BMI. The authors discuss limitations in the data set and its interpretability. The authors establish a normative data set after developing a standardized recording protocol and test meal and show that EGG recordings can be obtained reliably in the pediatric population. Development of similar norms by investigators using the EGG is crucial for future exploration of the validity and clinical application of the EGG. Differences in test conditions of signal detection and analytic methods influence EGG results substantially, and caution should be used when comparing results across centers.

Adolescent↗
PubMed2001

Is maternal underweight really a risk factor for adverse pregnancy outcome? A population-based study in London.

OBJECTIVE: To determine the maternal and fetal risk of adverse outcome during pregnancy in relation to low maternal body mass index in an unselected population. DESIGN: Retrospective analysis. METHODS: Information for the years between 1988 and 1997 was extracted from a validated maternity database, including all but one of the maternity units in the North West Thames Region; 215,105 completed singleton pregnancies were studied. Comparison of pregnancy outcome was made on the basis of maternal body mass index at booking. There were 176,923 with a normal weight body mass index ( = 20 < 25). There were 38,182 with an underweight body mass index (< 20). Comparisons included antenatal complications (e.g. gestational diabetes, pre-eclampsia); intervention in labour, maternal morbidities (e.g. infection, postpartum haemorrhage, pulmonary thromboembolism); and neonatal outcome (admitted to special care baby unit at 24 hour of age, gestation at delivery, birthweight, stillbirth). Data are presented as percentages of outcomes in the normal and underweight groups with adjusted odds ratios and confidence intervals according to body mass index group. RESULTS: In the underweight group only antenatal anaemia, preterm delivery and birthweight below the 5th centile were more frequent than in women of normal body mass index. The prevalence of certain complications, including development of gestational diabetes mellitus, pre-eclampsia, obstetric intervention and postpartum haemorrhage, were significantly lower in those with low body mass index. CONCLUSION: Low maternal body mass index is associated with increased prevalence of some pregnancy complications, notably preterm delivery and low birthweight, but overall the outcome is favourable and several adverse outcomes are less common in this group of women.

Body Mass Index↗
PubMed2001

One principle and three fallacies of disability studies.

My critics in this symposium illustrate one principle and three fallacies of disability studies. The principle, which we all share, is that all persons are equal and none are less equal than others. No disability, however slight, nor however severe, implies lesser moral, political or ethical status, worth or value. This is a version of the principle of equality. The three fallacies exhibited by some or all of my critics are the following: (1) Choosing to repair damage or dysfunction or to enhance function, implies either that the previous state is intolerable or that the person in that state is of lesser value or indicates that the individual in that state has a life that is not worthwhile or not thoroughly worth living. None of these implications hold. (2) Exercising choice in reproduction with the aim of producing children who will be either less damaged or diseased, or more healthy, or who will have enhanced capacities, violates the principle or equality. It does not. (3) Disability or impairment must be defined relative either to normalcy, "normal species functioning", or "species typical functioning". It is not necessarily so defined.

Abortion, Induced↗
PubMed2001

The cervicocranium: its radiographic assessment.

Acute injuries of the cervicocranium (from the occiput to the second cervical intervertebral disk) may be radiographically obscure due to minimal displacement of fracture fragments, minor alterations of normal anatomic relationships (occipitoatlantal subluxation), or superimposition of normal skeletal structures. With the nasooropharynx adequately distended with air, the normal cervicocranial prevertebral soft-tissue contour is congruent with the anterior cortical margin of the cervicocranium; namely, concave above, convex anterior to, and concave below the anterior tubercle of C1. Alterations of the normal cervicocranial prevertebral soft-tissue contour due to hemorrhage into the retropharyngeal fascial space from subtle fractures or ligamentous injuries should prompt further assessment of the cervicocranium by means of computed tomography (CT). Cervicocranial CT prompted by an abnormal cervicocranial prevertebral soft-tissue contour has yielded a 16% positive injury rate, approximately three times the rate of acute cervical spine injuries reported in the literature.

Adult↗
PubMed2001

Use of molecular probes to assess geographic distribution of Pfiesteria species.

We have developed multiple polymerase chain reaction (PCR)-based methods for the detection of Pfiesteria sp. in cultures and environmental samples. More than 2,100 water and sediment samples from estuarine sites of the U.S. Atlantic and gulf coasts were assayed for the presence of Pfiesteria piscicida Steidinger & Burkholder and Pfiesteria shumwayae Glasgow & Burkholder by PCR probing of extracted DNA. Positive results were found in about 3% of samples derived from routine monitoring of coastal waters and about 8% of sediments. The geographic range of both species was the same, ranging from New York to Texas. Pfiesteria spp. are likely common and generally benign inhabitants of coastal areas, but their presence maintains a potential for fish and human health problems.

Animals↗
PubMed2001

Adjuvant and neoadjuvant therapies of pancreatic cancer: a review.

The survival of patients diagnosed with pancreatic cancer is dismal. Few patients on initial presentation are suitable for surgical resection. This has prompted clinical studies with chemotherapy and/or radiotherapy designed either to increase the number of patients eligible for surgery (neoadjuvant therapy) or to prolong the survival of patients who had undergone surgery (adjuvant therapy). None of these studies may at this time be considered definitive. Wherever possible, patients felt eligible for neoadjuvant or adjuvant therapy should be entered on clinical trials. Where this is not possible, clinicians should exercise their best judgment in offering this type of treatment to pancreatic cancer patients under their care.

Chemotherapy, Adjuvant↗
PubMed2001

User satisfaction: measurement and interpretation.

Over the past 5 years there has been an increased interest in assessing users' satisfaction with health care services in England. Measuring and interpreting user satisfaction with reproductive and sexual health services can be complex, and efforts have met with varying degrees of success. This paper will summarise the methods that have been used to assess user satisfaction over the past 10 years, describe a different type of approach that has been recently used in England, and provide some suggestions for approaches that may be effective in improving clinical effectiveness in the new millennium.

Family Planning Services↗