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Biomedical subjects

J Harvey

Publications and source records attributed to J Harvey.

At least 55 records · Page 3Linked to original sources
PubMed2000

Vagus nerve stimulation therapy for epilepsy in older adults.

The authors assessed the efficacy, safety, and tolerability of vagus nerve stimulation (VNS) for refractory epilepsy in 45 adults 50 years of age and older. They determined seizure frequency, adverse effects, and quality of life. At 3 months, 12 patients had a >50% decrease in seizure frequency; at 1 year, 21 of 31 studied individuals had a >50% seizure decrease. Side effects were mild and transient. Quality of life scores improved significantly with time.

Electric Stimulation↗
PubMed2000

Essential role of phosphoinositide 3-kinase in leptin-induced K(ATP) channel activation in the rat CRI-G1 insulinoma cell line.

The mechanism by which leptin increases ATP-sensitive K(+) (K(ATP)) channel activity was investigated using the insulin-secreting cell line, CRI-G1. Wortmannin and LY 294002, inhibitors of phosphoinositide 3-kinase (PI3-kinase), prevented activation of K(ATP) channels by leptin. The inositol phospholipids phosphatidylinositol bisphosphate and phosphatidylinositol trisphosphate (PtdIns(3,4,5)P(3)) mimicked the effect of leptin by increasing K(ATP) channel activity in whole-cell and inside-out current recordings. LY 294002 prevented phosphatidylinositol bisphosphate, but not PtdIns(3,4,5)P(3), from increasing K(ATP) channel activity, consistent with the latter lipid acting as a membrane-associated messenger linking leptin receptor activation and K(ATP) channels. Signaling cascades, activated downstream from PI 3-kinase, utilizing PtdIns(3,4,5)P(3) as a second messenger and commonly associated with insulin and cytokine action (MAPK, p70 ribosomal protein-S6 kinase, stress-activated protein kinase 2, p38 MAPK, and protein kinase B), do not appear to be involved in leptin-mediated activation of K(ATP) channels in this cell line. Although PtdIns(3,4,5)P(3) appears a plausible and attractive candidate for the messenger that couples K(ATP) channels to leptin receptor activation, direct measurement of PtdIns(3,4,5)P(3) demonstrated that insulin, but not leptin, increased global cellular levels of PtdIns(3,4,5)P(3). Possible mechanisms to explain the involvement of PI 3-kinases in K(ATP) channel regulation are discussed.

Adenosine Triphosphate↗
PubMed2000

Mortality of sea lions along the central California coast linked to a toxic diatom bloom.

Over 400 California sea lions (Zalophus californianus) died and many others displayed signs of neurological dysfunction along the central California coast during May and June 1998. A bloom of Pseudo-nitzschia australis (diatom) was observed in the Monterey Bay region during the same period. This bloom was associated with production of domoic acid (DA), a neurotoxin that was also detected in planktivorous fish, including the northern anchovy (Engraulis mordax), and in sea lion body fluids. These and other concurrent observations demonstrate the trophic transfer of DA resulting in marine mammal mortality. In contrast to fish, blue mussels (Mytilus edulus) collected during the DA outbreak contained no DA or only trace amounts. Such findings reveal that monitoring of mussel toxicity alone does not necessarily provide adequate warning of DA entering the food web at levels sufficient to harm marine wildlife and perhaps humans.

Animals↗
PubMed2000

Medical student appraisal of interactive computer-assisted learning programs embedded in a general pathology course.

Computer-assisted learning programs (CALs) were embedded in a course on general pathology for medical students at the University of Edinburgh Medical School. Students' reactions to the programs were evaluated. Students completed written questionnaires and were interviewed and observed as they used the CALs. Students liked the CALs and felt that they were integrated with other parts of their teaching and aided them in understanding the subject material. Different question styles were variably appreciated. The most useful aspects of the CALs were the interactive parts (questions and answers), summaries, pictures, learning at the individual's own pace, and question practice, especially with MCQs. Students found the CALs an effective learning tool, particularly when linked with other course components as a complement to, rather than a replacement for, other learning methods.

Computer-Assisted Instruction↗
PubMed2000

Male gender predisposes to development of endotoxic shock in the rat.

OBJECTIVE: After intravenous (i.v.) injection of lipopolysaccharide (LPS) macrophages release nitric oxide (NO) due to the expression of the inducible NO synthase (iNOS). After LPS NO is abundantly produced also in the cardiovascular system and may contribute to the development of hypotension and shock. Since the immune response, the synthesis of NO and the regulation of blood pressure (BP) differ between males and females, in the present study the effect of LPS on BP, renal function, the plasma and urinary concentration of the metabolites of NO as well as the splenic and aortic expression of the iNOS gene were compared between male and female rats. METHODS: BP and renal function were measured in anesthetized rats following the i.v. injection of LPS (E. coli, 4 mg/kg). The NO2- and NO3- (metabolites of NO=NOx) concentration was measured by the Griess reaction. The iNOS gene expression was studied by RT-PCR. RESULTS: Four hours after LPS, BP of males (n=9) was reduced by 63+/-12 mmHg versus 10+/-4 in females (n=7, P<0.005). Aminoguanidine, a selective inhibitor of iNOS, prevented the reduction of BP in males. The plasma concentration of NOx (P(NOx)), microM) was lower in hypotensive males (128+/-20) than in normotensive females (235+/-29, P<0.005). Males also exhibited lower urinary NOx excretion (U(NOx)V) after LPS (P<0.001 vs. females). Prior castration of males provided protection against hypotension (fall of BP: -4+/-4 mmHg, n=6, P<0.02 versus males) and resulted in higher P(NOx) as well as U(NOx)V (both P<0.001 versus males and not different from females). Prior ovariectomy (n=5) had no influence on the hemodynamic and NOx response to LPS. Male rats displayed enhanced aortic iNOS/beta-actin ratio relative to females after LPS (n=3 in each group, P<0.05). CONCLUSIONS: (1) Male gender may sensitize to LPS-induced shock and (2) sensitivity of males to endotoxin is associated with an attenuated, not exaggerated total rate of NO synthesis.

Animals↗
PubMed2000

Functional expression of cell surface cannabinoid CB(1) receptors on presynaptic inhibitory terminals in cultured rat hippocampal neurons.

At present, little is known about the mechanisms by which cannabinoids exert their effects on the central nervous system. In this study, fluorescence imaging and electrophysiological techniques were used to investigate the functional relationship between cell surface cannabinoid type 1 (CB(1)) receptors and GABAergic synaptic transmission in cultured hippocampal neurons. CB(1) receptors were labelled on living neurons using a polyclonal antibody directed against the N-terminal 77 amino acid residues of the rat cloned CB(1) receptor. Highly punctate CB(1) receptor labelling was observed on fine axons and at axonal growth cones, with little somatic labelling. The majority of these sites were associated with synaptic terminals, identified either with immunohistochemical markers or by using the styryl dye FM1-43 to label synaptic vesicles that had undergone active turnover. Dual labelling of neurons for CB(1) receptors with either the inhibitory neurotransmitter GABA or its synthesising enzyme glutamate decarboxylase, demonstrated a strong correspondence. The immunocytochemical data was supported by functional studies using whole-cell patch-clamp recordings of miniature inhibitory postsynaptic currents (mIPSCs). The cannabinoid agonist WIN55,212-2 (100nM) markedly inhibited (by 77+/-6.3%) the frequency of pharmacologically-isolated GABAergic mIPSCs. The effects of WIN55,212-2 were blocked in the presence of the selective CB(1) receptor antagonist SR141716A (100nM).In conclusion, the present data show that cell surface CB(1) receptors are expressed at presynaptic GABAergic terminals, where their activation inhibits GABA release. Their presence on growth cones could indicate a role in the targeting of inhibitory connections during development.

Animals↗
PubMed2000

Assessment of endothelial cell proliferation in primary breast carcinoma and its association with axillary lymph node status.

The correlation between angiogenesis as assessed by endothelial cell proliferation in blood/lymphatic vessels in primary breast carcinomas, and axillary lymph-node metastasis was studied using a case-control design. Primary breast carcinomas, < 2 cm in diameter, from 26 axillary node positive patients (case), were compared with neoplasms from 45 node-negative patients (control). Vascularity, as assessed by vessel density, and endothelial cell proliferation were measured in a single tissue section using a double immunohistochemical staining technique using MIBI (Ki-67) and FVIII antibodies. No association between vascularity and node status was found (P > 0.70). Node positive breast carcinomas had, on average, significantly smaller proliferating vessels (140+/-7 microm in perimeter) in the primary lesion when compared with node negative tumours (164+/-7 microm in perimeter (P < 0.02). In addition, the frequency of relatively small vessels (less than 180 microm in perimeter) with proliferating endothelium was higher in node positive carcinomas than lymph-node negative neoplasms (P < 0.03). This association between node status and the size and frequency of blood/lymphatic vessels with proliferating endothelium in primary carcinoma may have important implications in metastasis.

Journal Article↗
PubMed2000

Causes of involutional ectropion and entropion--age-related tarsal changes are the key.

PURPOSE: To measure tarsal plates across various age-groups, to determine whether tarsal size changes with increasing age and whether size correlates with involutional ectropion and entropion. METHODS: Comparative, observational, case-control study design. Data were obtained for length and height of tarsus in each of the four eyelids. The data were constructed to determine: (I) right-to-left-side comparison data, (II) sex difference data, (III) age normal data, (IV) involutional entropion data, (V) involutional ectropion data. RESULTS: (I) There is no difference in tarsal dimensions between right and left sides; (II) males have larger tarsal dimensions than females; (III) tarsal plates are on average smaller in older age ranges; (IV) patients with entropion have smaller than average age-normal tarsal plates; (V) patients with ectropion have larger than average age-normal tarsal plates. CONCLUSIONS: (I) Right and left tarsal plates have equal dimensions, and involutional changes likely occur on both right and left sides equally frequently; (II) males have larger tarsal plates than females and entropion is more frequent in females and ectropion in males; (III) tarsal plates may have a general tendency to atrophy or shrink with age; this may explain why some eyelids develop entropion and others ectropion; (IV) entropion results from the mechanical effect of an atrophied or smaller than age-normal, partially or fully disinserted, tarsal plate being overcome by the normal or increased tone of the preseptal/pretarsal orbicularis muscle; (V) ectropion results from an age-normal or larger than normal tarsal plate mechanically overcoming the normal or decreased tone of the preseptal/pretarsal orbicularis muscle in combination with medial/lateral canthal tendon laxity.

Adult↗
PubMed2000

Antigen-specific responses to diphtheria-tetanus-acellular pertussis vaccine in human infants are initially Th2 polarized.

Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization. Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines, but detailed investigations on vaccine immunity during infancy have not yet been undertaken. We report below the results of a comprehensive prospective study on responses to the tetanus component of the diphtheria, tetanus, acellular pertussis (DTaP) vaccine in a cohort of 55 healthy children, employing peripheral blood mononuclear cells (PBMC) collected at the 2-, 4-, and 6-month vaccinations and at 12 months. Antigen-specific production of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, IL-13, and gamma interferon (IFN-gamma) was determined at each sample point, in parallel with polyclonal (phytohemagglutinin PHA-induced) cytokine responses. Our results indicate early and persistent Th2 responses to the vaccine, in contrast to a more delayed and transient pattern of IFN-gamma production. This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production, suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system.

Age Factors↗
PubMed2000

Chlamydia trachomatis screening in young people in Merseyside.

OBJECTIVES: To evaluate the acceptability to young people of proactive Chlamydia trachomatis (CT) information and urine test. To discover the extent of CT infection and the practical implications for completing treatment and partner notification. DESIGN: Prospective screening with sexual health questionnaire. SETTING: Three family planning clinics for young people in Liverpool and South Sefton. PARTICIPANTS: Nine hundred and five women and 53 men had urine tests and answered the questionnaire. All aged 20 years or under attending the clinics were given information about CT and safer sex. MAIN OUTCOME MEASURES: The acceptability of proactive information and screening for CT using a urine test. Prevalence of CT infection. The time and effort incurred informing and managing those testing positive. RESULTS: The information and urine test were readily accepted. Prevalence of CT was 8.5% in women and 5.7% in men. More than three-quarters of those testing positive were treated, but it took much time and effort, as follow-up attendance was poor. CONCLUSIONS: The prevalence of CT was high in this population. Young people participated in screening readily. They are interested in this health issue, but it was difficult to hold their attention long enough to complete the process of treatment and contact tracing. Completing this successfully either needs a huge input of resources or a new approach. These results have led to the piloting of an outreach health adviser administering treatment and carrying out partner notification at the screening site. Some of the questions raised by the CMO have been addressed.

Adolescent↗
PubMed2000

The productivity of primary care research networks.

Primary care research networks are being publicly funded in the United Kingdom to promote a culture of research and development in primary care. This paper discusses the organisational form of these networks and how their productivity can be evaluated, drawing on evidence from management science. An evaluation of a research network has to take account of the complexity of the organisation, the influence of its local context, and its stage of development. Output measures, such as number of research papers, and process measures, such as number of research meetings, may contribute to an evaluation. However, as networking relies on the development of informal, trust-based relationships, the quality of interactions within a network is of paramount importance for its success. Networks can audit and reflect on their success in promoting such relationships and a more formal qualitative evaluation by an independent observer can document their success to those responsible for funding.

Efficiency, Organizational↗
PubMed2000

Fifteen-year experience with pediatric renal transplantation at the Montefiore Medical Center.

At Montefiore Medical Center, 140 pediatric recipients have received 155 renal allografts over a 16-year period with an overall 6% mortality. Graft survival was not significantly different based upon race or sex of recipient. Graft survival was significantly better for first time transplants and the youngest recipients. Graft survival was significantly improved using Tacrolimus immunosuppression.

Academic Medical Centers↗
PubMed1999

Bioavailability of interferon beta 1b in MS patients with and without neutralizing antibodies.

BACKGROUND: Neutralizing antibodies (NAB) to interferon beta (IFNbeta) occur in about one-third of MS patients treated with IFNbeta-1b and there is an association with a loss of clinical and MRI efficacy. However, there are no data regarding the bioavailability of IFNbeta-1b in patients with and without NAB. METHODS: The authors measured MxA in whole blood by ELISA, and serum-binding antibodies (SBA) by Western blot and ELISA in 134 samples of MS patients on IFNbeta-1b and 54 control subjects, and correlated the MxA levels and SBA titers with the NAB titer. RESULTS: In the IFNbeta group 84 samples were NAB negative, 21 were NAB positive (i.e., titer of > or =20), and 29 had detectable NAB (i.e., titer between 10 and 20). The median MxA concentration in NAB-negative patients was 4.09 ng/10(5) peripheral blood leukocytes (PBL), 2.37 ng/10(5) PBL in samples with detectable NAB, 0.36 ng/10(5) PBL in NAB-positive samples, and 0.27 ng/10(5) PBL in control subjects. There was no significant difference between NAB-positive samples and control subjects, otherwise the groups differed significantly from each other. SBA occurred in 49% of NAB-negative samples, in 79% of samples with detectable NAB, and in all NAB-positive samples. With regard to the SBA titer, all groups differed significantly from each other. In none of the control samples were SBA detected. CONCLUSION: The conversion of SBA into NAB depends to some degree on the SBA titer, but other mechanisms may be involved. Once NAB have developed, the bioavailability of IFNbeta as measured by MxA is completely inhibited.

Antibodies↗
PubMed1999

Head circumference in ELBW babies is associated with learning difficulties and cognition but not ADHD in the school-aged child.

This study examines whether a small head circumference (HC) and low head-circumference growth velocity (HGV) during the first year of life predict consequences at school age in learning, cognition, and concentration. A total of 124 extremely-low-birthweight (ELBW) infants (birthweight 500 to 999 g) born between 1977 and 1986 were eligible for follow-up at the corrected ages of 4, 8, and 12 months and 2, 4, and 6 years. Infants were categorized as having a small HC (< 3% or 3 to 10%) on the basis of the 1990 British growth data which allowed standardized z-scores to be calculated for HC, independent of gestation and corrected age. HGV measurements were calculated using differences in the HC z-scores. In 1995, parents of 87 children agreed to participate in a study of learning and attention at school age. Attention-deficit-hyperactivity disorder (ADHD) was assessed using the Du Paul Rating Scale. Academic performances were based on a teacher questionnaire dealing with aspects of reading, writing, mathematics, and spelling. A child was considered to have a learning difficulty if academic problems were present in at least one of these four areas. Intellectual ability was assessed using the McCarthy Scale at 6 years. HC < 3% and 3 to 10% at 8 months' corrected age was strongly associated with school-aged learning problems (P=0.004), with a moderate specificity (70%), positive predictive value (PPV) (67%), and sensitivity (67%). HGV < or = 10% from birth to 4 months was also associated with learning problems at school age (P=0.01) with a higher specificity (98%) and PPV (88%) but lower sensitivity (20%). A logistic regression analysis was performed with the risk for learning difficulties at 8 months as the dependent variable. Sex, gestation, birthweight, multiple births, and a history of intraventricular hemorrhage did not substantially alter the unadjusted odds ratio (4.7; 95% CI 1.9 to 13.6). Maternal age and education did not confound the relation. No association was found between HC or HGV and ADHD. HC < 3% at 4 months (P<0.02), 8 months (P=0.02), and 12 months (P=0.04), and HGV between birth and 4 months (P<0.01) were significantly associated with low cognitive ability at 6 years.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Dual actions of the metabolic inhibitor, sodium azide on K(ATP) channel currents in the rat CRI-G1 insulinoma cell line.

1. The effects of various inhibitors of the mitochondrial electron transport chain on the activity of ATP-sensitive K+ channels were examined in the Cambridge rat insulinoma G1 (CRI-G1) cell line using a combination of whole cell and single channel recording techniques. 2. Whole cell current clamp recordings, with 5 mM ATP in the pipette, demonstrate that the mitochondrial uncoupler sodium azide (3 mM) rapidly hyperpolarizes CRI-G1 cells with a concomitant increase in K+ conductance. This is due to activation of K(ATP) channels as the sulphonylurea tolbutamide (100 microM) completely reversed the actions of azide. Other inhibitors of the mitochondrial electron transport chain, rotenone (10 microM) or oligomycin (2 microM) did not hyperpolarize CRI-G1 cells or increase K+ conductance. 3. In cell-attached recordings, bath application of 3 mM sodium azide (in the absence of glucose) resulted in a rapid increase in K(ATP) channel activity, an action readily reversible by tolbutamide (100 microM). Application of sodium azide (3 mM), in the presence of Mg-ATP, to the intracellular surface of excised inside-out patches also increased K(ATP) channel activity, in a reversible manner. 4. In contrast, rotenone (10 microM) or oligomycin (2 microM) did not increase K(ATP) channel activity in either cell-attached, in the absence of glucose, or inside-out membrane patch recordings. 5. Addition of sodium azide (3 mM) to the intracellular surface of inside-out membrane patches in the presence of Mg-free ATP or the non-hydrolysable analogue 5'-adenylylimidodiphosphate (AMP-PNP) inhibited, rather than increased, K(ATP) channel activity. 6. In conclusion, sodium azide, but not rotenone or oligomycin, directly activates K(ATP) channels in CRI-G1 insulin secreting cells. This action of azide is similar to that reported previously for diazoxide.

Adenosine Triphosphate↗
PubMed1999

Estimating the prevalence of problem drug use in inner London: a discussion of three capture-recapture studies.

AIMS: To provide an evidence base of estimates of the prevalence of problem drug use in inner London. DESIGN: Re-analysis of three capture-recapture studies using subjects aged 15-49 years, that aim to estimate the hidden population from analysing the overlaps between three data sources. SETTING: Newham (1995) Camden and Islington (C&I) (1993/4) and Lambeth, Southwark and Lewisham (LSL) (1992). PARTICIPANTS: Each study collected data from three sources of problem drug users including: the Regional Drug Misuse Database, specialist drug agencies, HIV tests, social services, police arrests and court records. In LSL opiate users were analysed separately. The studies identified 1832 individuals in LSL, 543 in Newham, and 1321 in C&I. MEASUREMENTS: Poisson models were fitted to the data testing different interactions between the data sources representing potential dependencies. The simplest model was selected on the basis of its AIC score and log-likelihood ratio tests. FINDINGS: The number of hidden problem drug users were estimated to be 12,500 (95% CI 9600-16,100) in LSL with 4400 (3200-6100) opiate users; 7000 (5000-10,000) in C&I and 3800 (2000-7200) in Newham. The prevalence of problem drug use in those aged 15-49 was estimated to be 3.1% (2.5-3.9%) in LSL with 1.3% (1.0-1.6%) opiate users; and 3.6% (2.7-4.9%) and 3.3% (1.9-5.7%) in C&I and Newham, respectively. CONCLUSIONS: Despite the inherent problems with capture-recapture methods, our three studies establish an evidence base for estimates of problem drug use in London. It is important that a larger study is carried out in London.

Adolescent↗
PubMed1999

Biological properties of interferon-alpha produced Ex vivo by whole blood of patients infected by human immunodeficiency virus-1.

We investigated the biological properties of interferon (IFN)-alpha produced by Sendai virus (SV)-activated whole blood cultures in 20 patients infected with human immunodeficiency virus (HIV)-1 and 24 healthy controls. Supernatants of cultures were assayed for IFN-alpha by using an immunological method (DELFIA), biological methods and an in-vitro MxA induction assay. The levels of intracellular MxA protein were detected by an immunochemiluminescence assay. The levels of IFN-alpha in patients measured by DELFIA were significantly lower than those in healthy controls (P < 0.0001), but the antiviral activity of IFN-alpha in patients infected with HIV-1 was lower than predicted from DELFIA. The IFN-alpha produced by cells of patients infected with HIV-1 was able to induce MxA protein in human amnions WISH cells but was unable to protect these cells against Vesicular Stomatitis Virus (VSV)-induced cytopathic effects. A relative increased capability to induce the production of MxA protein in vitro was observed with the IFN-alpha contained in culture supernatant of virus-activated whole blood of HIV-1-infected patients with increased levels of MxA in their peripheral blood. These data suggest that biological properties of IFN-alpha produced in the course of HIV-1 infection are different from those observed with IFN-alpha of healthy subjects.

Acquired Immunodeficiency Syndrome↗