Biomedical subjects

S Holland

Publications and source records attributed to S Holland.

At least 37 records · Page 2Linked to original sources

PubMed2000

Comparison of serum catalytic activity and immunoreactivity of bone alkaline phosphatase in hypophosphatasia.

Hypophosphatasia is a rare bone disorder characterised by low levels of tissue non-specific alkaline phosphatase (TNSALP). Although TNSALP is widespread in virtually all tissues the clinical effects, when produced, seem only to affect the mineralizing tissue such as teeth and skeleton. The skeleton is severely affected in the perinatal form of the disease, when death may occur in utero, or may not be affected in the adult type variety of the disease. We therefore compared the catalytic (cBALP) and immunoreactivity (iBALP) of bone alkaline phosphatase isoenzyme in six families with hypophosphatasia. iBALP was measured using an IRMA method. cBALP was measured after electrophoretic separation of serum alkaline phosphatase isoenzymes on lectin containing agarose gel. The percentage of different isoenzymes was calculated using densitometric scanning and cBALP calculated from the known total serum alkaline phosphatase activity. Results showed cBALP=0.796+3. 269iBALP, r=0.9 p<0.01, in cases of hypophosphatasia. In general, the lower the iBALP and cBALP the more severe the skeletal disease. The bone isoenzyme level predicts the clinical severity of bone disease.

Adult↗

PubMed2000

Determination of plate source, detector separation from one signal

We address the problem of locating a transient source, such as an acoustic emission source, in a plate. We apply time-frequency analysis to the signals detected at a receiver. These highly dispersive and complex waveforms are measured for source-receiver separations ranging from 40 to 180 plate thicknesses and at frequencies such that 10 to 20 Rayleigh-Lamb branches are included. Reassigned, smoothed, pseudo-Wigner-Ville distributions are generated that exhibit the expected sharp ridges in the time-frequency plane, lying along the predicted frequency-time-of-arrival relations. The source-receiver separation can be determined from such plots.

Journal Article↗

PubMed2000

Montelukast adult (10-mg film-coated tablet) and pediatric (5-mg chewable tablet) dose selections.

Montelukast is a selective leukotriene receptor antagonist that has been shown to be effective in the treatment of chronic asthma. It is approved in more than 70 countries for patients 6 years of age and older. For adults (> or = 15 years of age), a 10-mg film-coated tablet (FCT) is available, and for children (aged 6 to 14 years), a 5-mg chewable tablet (CT) is available. The adult montelukast dose (10-mg FCT) was selected on the basis of classic dose-ranging studies as the lowest dose that produces maximal improvement in both measures of airway function and patient-reported outcomes in chronic asthma and in the attenuation of exercise-induced bronchoconstriction. The strategy used for the pediatric dose selection for montelukast was based on the determination of a CT dose that would provide an overall systemic exposure to montelukast in children similar to that in adults who receive a 10-mg FCT dose. Because montelukast was to be given chronically for the treatment of asthma, the area under the plasma concentration-time curve was considered to be the pharmacokinetic measurement that best represented systemic exposure to the drug. A 5-mg CT yielded a comparable single-dose area under the plasma concentration-time curve profile to that of the adult 10-mg FCT dose and, therefore, was selected as the pediatric dose for children aged 6 to 14 years with asthma. Subsequently, 2 studies of efficacy and tolerability validated the choice of the 5-mg CT dose.

Acetates↗

PubMed2000

Knowledge about HIV/AIDS, the perceived risks of infection and sources of information of Asian-Indian adolescents born in the USA.

This study examined the extent and specificity of knowledge about HIV/AIDS, the most used sources of information and the usefulness of these sources among Asian-Indian adolescents who were born in the USA and whose parents emigrated from India. Although 86% knew that having unsafe sex with a person infected with HIV could transmit HIV, 47% did not know that sharing a razor with an HIV-positive person could do so, and a significant proportion believed that donating blood (27%) and taking blood tests (14%) could transmit HIV. Television was the most used source of information, but school programmes on HIV/AIDS were considered the most useful source. The results indicated that to be effective, HIV/AIDS prevention programmes must assess the gap in scientific knowledge and beliefs, and clarify misconceptions, reinforce school programmes to present clear messages about the transmission of HIV/AIDS and utilize television to reach adolescents.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Nck-interacting Ste20 kinase couples Eph receptors to c-Jun N-terminal kinase and integrin activation.

The mammalian Ste20 kinase Nck-interacting kinase (NIK) specifically activates the c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase module. NIK also binds the SH3 domains of the SH2/SH3 adapter protein Nck. To determine whether Nck functions as an adapter to couple NIK to a receptor tyrosine kinase signaling pathway, we determined whether NIK is activated by Eph receptors (EphR). EphRs constitute the largest family of receptor tyrosine kinases (RTK), and members of this family play important roles in patterning of the nervous and vascular systems. In this report, we show that NIK kinase activity is specifically increased in cells stimulated by two EphRs, EphB1 and EphB2. EphB1 kinase activity and phosphorylation of a juxtamembrane tyrosine (Y594), conserved in all Eph receptors, are both critical for NIK activation by EphB1. Although pY594 in the EphB1R has previously been shown to bind the SH2 domain of Nck, we found that stimulation of EphB1 and EphB2 led predominantly to a complex between NIK/Nck, p62(dok), RasGAP, and an unidentified 145-kDa tyrosine-phosphorylated protein. Tyrosine-phosphorylated p62(dok) most probably binds directly to the SH2 domain of Nck and RasGAP and indirectly to NIK bound to the SH3 domain of Nck. We found that NIK activation is also critical for coupling EphB1R to biological responses that include the activation of integrins and JNK by EphB1. Taken together, these findings support a model in which the recruitment of the Ste20 kinase NIK to phosphotyrosine-containing proteins by Nck is an important proximal step in the signaling cascade downstream of EphRs.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Alkaline phosphatase isoenzymes and clinical features in hypophosphatasia.

Hypophosphatasia is an hereditary disease characterized by low activity of total serum alkaline phosphatase (TALP) accompanied by a range of skeletal diseases. We have measured the main circulating alkaline phosphatase isoenzymes--bone (BALP), liver (LALP), intestinal (IALP), placental (PALP)--in six families with hypophosphatasia, using kinetic and electrophorectic methods. Our observations show that patients with skeletal disease tend to have a very low BALP activity. Patients even with undetectable LALP activity do not appear to manifest any clinical complications. Patients also showed proportionately high IALP activity. Since the production of significant IALP activity is not a constant feature in all healthy individuals, it remains to be established whether the survival of one of these patients (IALP > 80% of TALP) depended on the presence of circulating IALP.

Adult↗

PubMed2000

Routine coagulation screening in the management of emergency admission for epistaxis--is it necessary?

The role of routine coagulation studies in the management of patients suffering from epistaxis is unclear. In an attempt to address this issue the case notes of all emergency admissions for epistaxis to a large Scottish teaching hospital were retrospectively reviewed over a one-year period. One hundred and forty patients (63 male, 77 female) were admitted between January and December 1998. The patients who had coagulation studies were identified and their results analysed. A total of 121 patients (86.4 per cent) had coagulation studies performed. Of these, 10 (8.3 per cent) had abnormal results and all were taking warfarin or a combination of warfarin and aspirin. No other coagulation abnormalities were identified. This study supports the view that there does not appear to be a role for routine coagulation studies in patients admitted with epistaxis. The investigation for potential haemostatic disorders should be performed when clinically indicated and, if necessary, in consultation with the haematology service.

Adolescent↗

PubMed1999

Coagulation studies in patients admitted with epistaxis--current practice in Scotland.

Epistaxis remains the most common ENT emergency. The use of coagulation studies in Scotland to manage these patients was investigated to determine current practice. The study took the form of a postal questionnaire sent to all practising ENT consultants and a telephone survey of ENT senior house officers working in Scotland. Of the 60 questionnaires circulated amongst consultants, 55 responses were received (92 per cent). Thirty-eight consultants (70 per cent) indicated that they did not routinely request a coagulation screen for their patients, however, 30 per cent (16) did. Forty-three of the 45 junior staff were available for interview, 22 (51 per cent) of whom routinely requested coagulation studies. While the majority of consultants did not request routine coagulation studies, there did not appear to be any consensus among the junior staff. Although there is a paucity of scientific information with regard to this aspect of epistaxis patient management, there is support in the literature for targeted rather than blanket testing. There is perhaps a need to address this issue within individual departments, to achieve uniformity of practice, and to improve communication between junior and senior staff.

Blood Coagulation↗

PubMed1999

Peer networks, parental attributes, and drug use among Asian-Indian adolescents born in the United States.

This study examined the interrelationships among peer networks, parental attributes, and drug use among Asian-Indian adolescents born in the United States whose parents emigrated from India. The sample consisted of 200 Asian-Indian adolescents, 116 males and 84 females, aged 13 to 18, who were born in the United States and resided in the greater New York metropolitan area. The subjects were interviewed using a semistructured instrument adapted from relevant validated scales and items from other researchers. Adolescent-reported data were analyzed using descriptive and univariable techniques. Of the 200 subjects, 32.5% had tried some form of tobacco, alcohol, or other drug, and 67.5% did not report drug use of any kind. The adolescents stated whether they had ever (at least one time) smoked cigarettes (16.5%), drank beer (18%), drank wine (20.5%), or smoked marijuana (2.5%). The parents' communication of the harmful consequences of drug use and approval of the adolescents' peer networks correlated (p < .05) independently with less drug use by the adolescents. The parents' concern for education was positively correlated (p < .05) with the adolescents' academic performance. The prevalence of drug use among Asian-Indian adolescents is low. Parents' awareness of their children's school performance, peer networks, and concerns related to the consequences of drug use can be used as an effective mechanism to communicate the prevention of drug use among adolescents.

Journal Article↗

PubMed1999

Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults.

Montelukast, an oral leukotriene-receptor antagonist, has demonstrated efficacy and tolerability for the treatment of chronic asthma in adults. A once-daily 10 mg dose (film-coated tablet) was selected as the optimal adult dose based on dose-ranging studies. Asthma is a similar disease and is treated with the same medications in children and adults. These observations suggested that a dose of montelukast in children providing overall drug exposure (i.e., montelukast plasma concentrations) similar to that of the 10 mg film-coated tablet dose in adults would be efficacious, well tolerated, and obviate the need for separate dose-ranging studies in children. Therefore, the dose of montelukast for 6- to 14-year-old children was selected by identifying the chewable tablet dose of montelukast yielding a single-dose area under the plasma concentration-time curve (AUC) comparable to that achieved with the adult 10 mg film-coated tablet dose. Based on this approach, which included dose normalization of data from several pediatric pharmacokinetic studies, a 5 mg chewable tablet dose of montelukast was selected for use in clinical efficacy studies in 6- to 14-year-old children with asthma.

Acetates↗

PubMed1999

Effect of multiple doses of montelukast, a CysLT1 receptor antagonist, on digoxin pharmacokinetics in healthy volunteers.

The effect of multiple oral doses of montelukast, a cysLT1 receptor antagonist, on the pharmacokinetics of oral digoxin was studied in healthy male volunteers in a randomized double-blind two-period crossover study. Subjects received 10 mg of montelukast or placebo daily for 11 days. On day 7, they received a single 0.5 mg oral dose of digoxin elixir. The pharmacokinetic parameters of digoxin (AUC0-->24' AUC0-->infinity' Cmax' tmax' t1/2) and cumulative urinary excretion over 120 hours were not affected by the multiple doses of montelukast. The 90% confidence interval for each of these parameters fell within prespecified clinically acceptable bounds. Side effects were mild and transient. This suggests that concurrent administration of montelukast and digoxin was well tolerated. Concurrent treatment with montelukast has no effect on the pharmacokinetics of digoxin.

Acetates↗

PubMed1999

Teaching nursing ethics by cases: a personal perspective.

This article is a reflection on the use of case study material in the teaching of ethics to nursing students. Given the main aims of a course in ethics for nurses and the limited effectiveness of formal moral theory, it seems inevitable that the mainstay of nursing ethics courses will continue to be case study material. This approach has recently been criticized on a number of grounds. The author suggests here that disquiet over teaching ethics in this way should motivate a concern not with whether, but how, teaching by cases is to be undertaken.

Education, Nursing, Baccalaureate↗

PubMed1999

DNA studies underestimate the major role of CDKN2A inactivation in oral and oropharyngeal squamous cell carcinomas.

Loss of CDKN2A expression was demonstrated by immunohistochemistry in 87% of oral and oropharyngeal squamous cell carcinoma (OSCC) primary tumor samples. By contrast, DNA studies showed a much lower frequency of loss of the CDKN2A gene. Point mutations and promoter methylation of CDKN2A were seen in 7% and 23%, respectively, of primary tumors. Loss of heterozygosity analysis using a dense set of 9p markers showed allelic imbalance that included CDKN2A in only 31% of samples, but a further 47% showed loss at loci near CDKN2A with apparent retention of CDKN2A. No tumor with any allelic imbalance expressed CDKN2A, whether or not the imbalance appeared to involve the CDKN2A locus. We interpret these data as showing partially overlapping deletions on the two 9p homologues, with homozygous deletion of CDKN2A masked by amplification of contaminating stromal material. Our data show that inactivation of the CDKN2A gene products is a near-universal step in the development of oral and oropharyngeal squamous cell carcinomas, and we suggest that homozygous deletion is the most common mechanism of inactivation. The CDKN2A locus may be particularly prone to deletion because it encodes two unrelated tumor suppressor proteins, CDKN2A (p16INK4a) and p19ARF, and deletion, but not point mutation or methylation, would inactivate both gene products. However, our results also suggest that complex patterns of allelic imbalance in primary squamous carcinomas in general may not provide reliable evidence for the existence of multiple tumor suppressor genes within a single chromosomal region.

5' Untranslated Regions↗

PubMed1999

Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers.

Montelukast, a cysteinyl leukotriene receptor antagonist, is being developed for the treatment of asthma and related diseases. This study was designed to evaluate whether montelukast at clinically used dosage levels would interfere with the anticoagulant effect of warfarin. In a two-period, double-blind, randomized crossover study, 12 healthy male subjects received a single oral dose of 30 mg warfarin on the 7th day of a 12-day treatment with montelukast, 10 mg daily by mouth, or a placebo. Montelukast had no significant effect on the area under the plasma concentration-time curves and peak plasma concentrations of either R- or S-warfarin. However, slight but statistically significant decreases in time to peak concentration of both warfarin enantiomers and in elimination half-life of the less potent R-warfarin were observed in the presence of montelukast. These changes were not considered as clinically relevant. Montelukast had no significant effect on the anticoagulant effect of warfarin, as assessed by the international normalized ratio (INR) for prothrombin time (AUC0-144 and INR maximum). The results of this study suggest that a clinically important interaction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.

Acetates↗

PubMed1998

PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor.

Eph-related receptor tyrosine kinases (RTKs) have been implicated in intercellular communication during embryonic development. To elucidate their signal transduction pathways, we applied the yeast two-hybrid system. We could demonstrate that the carboxyl termini of the Eph-related RTKs EphA7, EphB2, EphB3, EphB5, and EphB6 interact with the PDZ domain of the ras-binding protein AF6. A mutational analysis revealed that six C-terminal residues of the receptors are involved in binding to the PDZ domain of AF6 in a sequence-specific fashion. Moreover, this PDZ domain also interacts with C-terminal sequences derived from other transmembrane receptors such as neurexins and the Notch ligand Jagged. In contrast to the association of EphB3 to the PDZ domain of AF6, the interaction with full-length AF6 clearly depends on the kinase activity of EphB3, suggesting a regulated mechanism for the PDZ-domain-mediated interaction. These data gave rise to the idea that the binding of AF6 to EphB3 occurs in a cooperative fashion because of synergistic effects involving different epitopes of both proteins. Moreover, in NIH 3T3 and NG108 cells endogenous AF6 is phosphorylated specifically by EphB3 and EphB2 in a ligand-dependent fashion. Our observations add the PDZ domain to the group of conserved protein modules such as Src-homology-2 (SH2) and phosphotyrosine-binding (PTB) domains that regulate signal transduction through their ability to mediate the interaction with RTKs.

3T3 Cells↗

PubMed1998

Epidemic keratoconjunctivitis outbreak at a tertiary referral eye care clinic.

An outbreak of epidemic keratoconjunctivitis (EKC) occurred at a tertiary referral eye care clinic between late September and mid-November 1995. Before the outbreak, instruments were cleaned with 70% isopropyl alcohol and handwashing between patients was not routine. Infection control measures were implemented when the outbreak was recognized in mid-October. Control measures included triaging suspected cases to a separate waiting area, cohorting cases to a specific examining room, endorsing the use of gloves and handwashing during examinations of patients, and cleaning instruments with a buffered bleach solution. Thirty-six cases were diagnosed before the infection control measures were taken, and 3 cases were seen after the control measures were taken. Also, numerous secondary cases occurred in the community. No additional cases were diagnosed from DEcember to February 25, 1996. Acquisition of the infection was linked to visits to 4 of 20 physicians in the eye clinic with 61% of cases associated with visits to 1 of those 4 physicians. The use of diagnostic lenses applied directly to the eye was associated with infection (odds ratio = 2.83, 95% confidence interval = 0.79 to 10.4), although this did not reach statistical significance. The use of tonometers, ophthalmic solutions, or laser therapy was not associated with infection, and all environmental cultures were negative. This outbreak emphasizes the need for implementation of routine infection control guidelines to prevent nosocomial transmission of epidemic keratoconjunctivitis and stresses the need for appropriate disinfection of instruments.

Adenoviridae Infections↗

PubMed1998

Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara.

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.

Carbohydrate Sequence↗

PubMed1998

Relationship between serum alkaline phosphatase and pyridoxal-5'-phosphate levels in hypophosphatasia.

1. Hypophosphatasia is a disorder characterized by low serum levels of alkaline phosphatase (ALP) and a range of skeletal deformities. The levels of a number of phosphorylated metabolites, namely phosphoethanolamine and pyrophosphate, are characteristically raised. Levels of pyridoxal-5'-phosphate (PLP) have also been reported to be raised. 2. Hypophosphatasia is a rare disease and experience of measuring PLP in patients is lacking. We have had the chance to look at PLP levels in four families with hypophosphatasia, specifically to examine the quantitative relationship between ALP and PLP which has not been described before. 3. We confirmed that PLP levels are raised in hypophosphatasia and related to the disease severity. A significant negative linear relationship was found between the log PLP and log ALP (log PLP = 5.99-2.76 log ALP; r = -0.85, P < 0.001). 4. Measurement of PLP is simpler than some of the phosphorylated compounds, e.g. pyrophosphate. PLP may be a useful measure in patients with a suspected diagnosis of hypophosphatasia or for screening family members to detect potential heterozygotes and to monitor any response to therapy. 5. There did not appear to be any adverse clinical effects in relation to disturbed vitamin B6 metabolism in hypophosphatasia. 6. Vitamin B6 is used therapeutically in a number of conditions with monitoring of PLP levels. In these conditions PLP levels should be interpreted in conjunction with the prevailing serum ALP levels as the metabolism of these compounds is closely inter-related.

Adult↗