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Biomedical subjects

N Moss

Publications and source records attributed to N Moss.

At least 19 recordsLinked to original sources
PubMed2006

Drape estimation vs. visual assessment for estimating postpartum hemorrhage.

OBJECTIVE: To compare (1) visual estimation of postpartum blood loss with estimation using a specifically designed blood collection drape and (2) the drape estimate with a measurement of blood loss by photospectrometry. METHODS: A randomized controlled study was performed with 123 women delivered at the District Hospital, Belgaum, India. The women were randomized to visual or drape estimation of blood loss. A subsample of 10 drape estimates was compared with photospectrometry results. RESULTS: The visual estimate of blood loss was 33% less than the drape estimate. The interclass correlation of the drape estimate to photospectrometry measurement was 0.92. CONCLUSION: Drape estimation of blood loss is more accurate than visual estimation and may have particular utility in the developing world. Prompt detection of postpartum hemorrhage may reduce maternal morbidity and mortality in low-resource settings.

Delivery, Obstetric↗
PubMed2003

Comparison of effects of GnRH and prostaglandin in combination, and prostaglandin on conception rates and time to conception in dairy cows.

OBJECTIVE: To assess the effectiveness of a gonadotrophin-releasing hormone (GnRH) / prostaglandin program (GnRH-PG-GnRH, Ovsynch) on conception rates and time to conception of lactating dairy cows compared with a PG program (double prostaglandin injection). DESIGN: A randomised multi-centre cohort study was conducted with 778 cows from nine dairy herds. Cows at different stages of lactation were randomly assigned, after matching for days open at the time of treatment, to either the PG or Ovsynch program. PROCEDURE: Cows on the PG program received two intramuscular injections of prostaglandin (2 mL, Prosolvin) 11 days apart. The Ovsynch program consisted of two intramuscular injections of GnRH (1 mL, Fertagyl) 9 days apart, separated by one injection of prostaglandin 40 h before the second GnRH injection. Milk samples were taken at the time of artificial insemination and assayed for progesterone by radioimmunoassay. RESULTS: The Ovsynch program was not significantly different to PG in achieving conception, with overall conception rates of 37.6% and 41.4%, respectively, for each program. There was, however, a significant interaction between the effects of parity and treatment (P = 0.03), because conception rates were higher in older cows (parity 5 or more) on the PG program than for older cows on the Ovsynch program. There was no significant effect of treatment (P > 0.5) on time to conception after treatment, but older cows were slower to conceive (P < 0.0001). Conception rates differed (P < 0.0001) among herds. CONCLUSION: The median days to conception for both groups was 22 and mean days from treatment to conception were 36.3 +/- 3.3 and 31.6 +/- 2.7 for the Ovsynch and PG programs respectively, indicating that reproductive performance of cows was not significantly different with Ovsynch program or PG program. There appears to be a need to evaluate causes of reproductive failure in older cows.

Aging↗
PubMed2002

Risk factors for repeat-breeder syndrome in New South Wales dairy cows.

A retrospective case-control study involving 1041 cow lactations from 10 commercial dairy herds in Australia determined relationships between biographic, production, reproductive and disease factors and repeat-breeder syndrome (RBS) (conception to greater than two inseminations). The study population was stratified into primiparous- and multiparous-cow sub-groups and logistic regression was used. Effects of herd were examined by including this variable alternatively as a fixed and a random effect. In the primiparous-cow fixed-effect model, the risk of RBS was increased with post-calving metritis, stillbirth, and with increasing days taken to reach peak milk yield, and reduced following dystocia. An inverted U-shaped relationship with total milk-solids percentage at the time of first service was detected. In the multiparous-cow fixed-effect model, the risk of RBS was increased in cows with chronic metritis, cystic ovarian disease (COD), in cows of parity >5 and in cows that were sub-fertile in the previous lactation. Increasing days to first recorded heat (DFH) reduced risk of RBS and a non-linear relationship with average 120-day milk-protein percentage was found. When herd was fitted as a random effect, stillbirth and 120-day average milk-protein percentage were no longer significant in the primiparous and multiparous models, respectively. The study emphasises the need to control appropriately for the clustering effect of herd and supports the need to minimise periparturient disease and improve nutrient balance to achieve optimal fertility in dairy herds.

Age Factors↗
PubMed2002

The epidemiology of subfertility in non-seasonal calving dairy herds in the Camden region of New South Wales: description of population and incidence.

OBJECTIVE: To describe biographic, reproductive, production and disease characteristics of 965 Holstein cows from 10 non-seasonal calving dairy herds in the Camden region of New South Wales, and to describe the incidence of subfertility, that is, conception requiring > 2 inseminations, in this population. DESIGN: A retrospective epidemiologic study. METHODS: Computer records were used to determine biographic, reproductive, production and disease characteristics in all lactations that commenced between 1 July 1995 and 30 June 1996 and resulted in conception during that lactation. Differences in these characteristics among herds and between primiparous and multiparous cows were examined. The lactational incidence of subfertility for lactations commencing during the study period was determined. RESULTS: Ten herds with appropriate records and management structures entered the study. Herd size ranged from 86 to 203 lactating cows. Nutritional and reproductive management of these herds was typical of smaller pasture-based herds within the study region. Records from 1320 cows were available, of which 965 were considered suitable for descriptive analysis. Monthly variations in number of cows calving were noted, with number of lactations commenced by primiparous and multiparous cows peaking in January and October, respectively. Significant (P < 0.001) inter-herd differences for all reproductive, disease and milk production outcomes were detected for both the entire population and within primiparous and multiparous subgroups. Of 1041 cows submitted for insemination, 76 failed to conceive. The lactational incidence rate (LIR) of subfertility in all lactations was 21.1% (95% CI 19-24%). and among all cows conceiving was 22.8% (95% Cl 20-25%). The LIR of subfertility in primipara was 24.1% (95% Cl 19-28%) and varied widely between herds (10%-40%). The LIR of subfertility in multipara was 22.2% (95% Cl 20-25%) and also varied widely between herds (7%-46%). CONCLUSION: Parity and herd of origin should be considered in any further analyses of these data.

Animals↗
PubMed2002

The epidemiology of subfertility in non-seasonal calving dairy herds in the Camden region of New South Wales: preliminary investigation of risk factors.

OBJECTIVE: To investigate relationships between biographic, reproductive, production and disease traits and subfertility among 965 Holstein cows from 10 non-seasonal calving dairy herds in the Camden region of New South Wales. DESIGN: A retrospective case-control study METHODS: Biographical, disease and reproductive data were collated from computerised records for cows with lactations that commenced between 1 July 1995 and 30 June 1996 and univariable and bivariable associations with subfertility were determined. RESULTS: Records from 965 cows that conceived were considered for risk factor analyses. Associations between subfertility and a number of risk factors (P < 0.3) were detected. Significant (P < 0.05) risk factors for subfertility in multiparous cows included herd of origin and, after controlling for the effect of herd, subfertility in the previous lactation, greater than 62 days dry, parity greater than five, interval between calving and first recorded heat, metritis and cystic ovarian disease. Herd of origin and, after controlling for herd effects, dystocia, metritis and percentage of milk fat plus protein at the time of first service were significant (P < 0.05) risk factors for subfertility in primiparous cows. The direction and magnitude of these associations are presented. CONCLUSION: Subfertility has a similar rate of occurrence in the herds examined to that reported overseas. Although herd of origin has a substantial effect on individual risk of subfertility, cow-level risk factors for subfertility are likely to exist. Exposures differ between primiparous and multiparous cows.

Animals↗
PubMed2001

Nonpeptidic, monocharged, cell permeable ligands for the p56lck SH2 domain.

p56lck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p56lck SH2 domain have the potential to disrupt the interaction of p56lck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p56lck SH2 domain (K(d) 1 microM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.

Caco-2 Cells↗
PubMed2001

Hepatic progenitors and strategies for liver cell therapies.

Liver cell therapies, including liver cell transplantation and bioartificial livers, are being developed as alternatives to whole liver transplantation for some patients with severe liver dysfunction. Hepatic progenitors are proposed as ideal cells for use in these liver cell therapies given their ability to expand extensively, differentiate into all mature liver cells, have minimal immunogenicity, be cryopreservable, and reconstitute liver tissue when transplanted. We summarize our ongoing efforts to develop clinical programs of hepatic progenitor cell therapies with a focus on hepatic stem cell biology and strategies that have emerged in analyzing that biology.

Animals↗
PubMed2001

Health for All in the Twenty-First Century, World Health Organization renewal, and equity in health: a commentary.

Health for All in the Twenty-first Century is the document presenting the global health policy adopted by the World Health Organization (WHO) in 1998, which reaffirms and updates the vision of Alma-Ata. This article provides a synopsis of the document and a commentary, concentrating on the issue of equity, which is central to WHO policy, and discussing cultural differences that underpin the notion of equity. The meaning of "equity" implies measurement, and the authors develop an approach to definitions of social strata and data issues that are used to quantify health differences. Finally, they discuss the way in which policies invoking equity are implemented into programs and present a rights-based approach as a case study of one way in which policy is being translated into action.

Health Plan Implementation↗
PubMed2000

Assessment of impact on health of residents living near the Nant-y-Gwyddon landfill site: retrospective analysis.

OBJECTIVES: To compare indices of health in a population living near a landfill site with a population matched for socioeconomic status and to review environmental monitoring data. DESIGN: Ecological study with small area statistics and environmental reports. SETTING: Electoral wards in valleys of South Wales. SUBJECTS: Populations in the five wards near the landfill site who had formally complained of odours (exposed population), and comparison populations in 22 wards in the same unitary authority within the same fifth of Townsend score. OUTCOME MEASURES: Mortality, rates of hospital admission, measures of reproductive health (proportion of all births and stillbirths of infants weighing <2500 g; rates of admissions for spontaneous abortion; rates of all reported congenital malformations). Environmental data on site emissions. RESULTS: There were no consistent differences in mortality, rates of hospital admissions, or proportion of low birthweight infants between the two populations. There was an increased maternal risk of having a baby with a congenital abnormality in residents near the site, both before its opening (relative risk 1.9; 95% confidence interval 1.3 to 2.85; P<0.001) and after (1.9; 1.23 to 2.95; P=0.003). Environmental monitoring showed that hydrogen sulphide from the site was probably responsible for odours. CONCLUSIONS: The area surrounding the landfill site has an increased rate of reported congenital malformations, which predated the opening of the landfill, although the cluster of cases of gastroschisis post-dated its opening. Several chemicals emitted from the site, including hydrogen sulphide and benzene, were found in air samples in the nearby community. Further studies of the reproductive risk in such communities are needed to examine the safety of waste disposal sites.

Congenital Abnormalities↗
PubMed2000

Socioeconomic disparities in health in the US: an agenda for action.

Inequality of income and wealth in the US has been growing rapidly since 1972. Evidence of socioeconomic effects on health is documented for many endpoints, and there is evidence that socioeconomic disparities in health are increasing. In Europe, equity in health and health care is a target of the World Health Organization, and has led to a variety of activities to reduce socioeconomic disparities in morbidity and mortality. In the US, activities in the public and private sectors have increased in recent years but attention, especially among the public-at-large in addition to elites, needs to be shifted to socioeconomic disparities. The paper suggests action strategies drawn from the European experience and other US efforts to place public health priorities on the policy agenda. A first step is to create a climate of unacceptability for socioeconomic disparities in health. Recommended activities include improvement and utilization of existing data; dissemination to broad audiences; building on existing initiatives; creating multi-sectoral alliances; formation of state and community task forces; attention to human capital as well as social justice issues; creative use of media; attraction of new funders; and implementation of quantitative targets.

Europe↗
PubMed1999

Ligands for the tyrosine kinase p56lck SH2 domain: discovery of potent dipeptide derivatives with monocharged, nonhydrolyzable phosphate replacements.

p56lck is a member of the src family of tyrosine kinases. Through modular binding units called SH2 domains, p56lck promotes phosphotyrosine-dependent protein-protein interactions and plays a critical role in signal transduction events that lead to T-cell activation. Starting from the phosphorylated dipeptide (2), a high-affinity ligand for the p56lck SH2 domain, we have designed novel dipeptides that contain monocharged, nonhydrolyzable phosphate group replacements and bind to the protein with KD's in the low micromolar range. Replacement of the phosphate group in phosphotyrosine-containing sequences by a (R/S)-hydroxyacetic (compound 8) or an oxamic acid (compound 10) moiety leads to hydrolytically stable, monocharged ligands, with 83- and 233-fold decreases in potency, respectively. This loss in binding affinity can be partially compensated for by incorporating large lipophilic groups at the inhibitor N-terminus. These groups provide up to 13-fold increases in potency depending on the nature of the phosphate replacement. The discovery of potent (2-3 microM), hydrolytically stable dipeptide derivatives, bearing only two charges at physiological pH, represents a significant step toward the discovery of compounds with cellular activity and the development of novel therapeutics for conditions associated with undesired T-cell proliferation.

Crystallography, X-Ray↗
PubMed1999

Phosphotyrosine-containing dipeptides as high-affinity ligands for the p56lck SH2 domain.

Src homology-2 (SH2) domains are noncatalytic motifs containing approximately 100 amino acid residues that are involved in intracellular signal transduction. The phosphotyrosine-containing tetrapeptide Ac-pYEEI binds to the SH2 domain of p56lck (Lck) with an affinity of 0.1 microM. Starting from Ac-pYEEI, we have designed potent antagonists of the Lck SH2 domain which are reduced in peptidic character and in which the three carboxyl groups have been eliminated. The two C-terminal amino acids (EI) have been replaced by benzylamine derivatives and the pY + 1 glutamic acid has been substituted with leucine. The best C-terminal fragment identified, (S)-1-(4-isopropylphenyl)ethylamine, binds to the Lck SH2 domain better than the C-terminal dipeptide EI. Molecular modeling suggests that the substituents at the 4-position of the phenyl ring occupy the pY + 3 lipophilic pocket in the SH2 domain originally occupied by the isoleucine side chain. This new series of phosphotyrosine-containing dipeptides binds to the Lck SH2 domain with potencies comparable to that of tetrapeptide 1.

Binding, Competitive↗
PubMed1999

Glycine improves survival after hemorrhagic shock in the rat.

This study investigated the effect of glycine on hemorrhagic shock in the rat. Rats were bled to maintain mean arterial pressure at 30-35 mm Hg for 1 h and subsequently resuscitated with 60% shed blood and lactated Ringer's solution. Only 20% of rats receiving saline just prior to resuscitation survived 72 h after shock. Survival was increased by glycine (11.2-90.0 mg/kg, i.v.) in a dose-dependent manner (half-maximal effect = 25 mg/kg) and reached maximal values of 78% at 45 mg/kg. Eighteen hours after resuscitation, creatinine phosphokinase increased 23-fold, transaminases increased 33-fold, and creatinine was elevated 2.4-fold, indicating injury to the heart, liver, and kidney, respectively. Pulmonary edema, leukocyte infiltration, and hemorrhage were also observed. In the kidney, proximal tubular necrosis, leukocyte infiltration, and severe hemorrhage in the outer medullary area occurred in rats receiving saline. Glycine reduced these pathological alterations significantly. It has been reported that oxidative stress and tumor necrosis factor(TNF)-alpha-production are involved in the pathophysiology of multiple-organ injury after shock. In this study, free radical production was increased 4-fold during shock, an effect blocked largely by glycine. Increases in intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by endotoxin were elevated significantly by hemorrhagic shock, alterations which were totally prevented by glycine. Taken together, it is concluded that glycine reduces organ injury and mortality caused by hemorrhagic shock by preventing free radical production and TNF-alpha formation.

Animals↗
PubMed1999

Dietary glycine and renal denervation prevents cyclosporin A-induced hydroxyl radical production in rat kidney.

Cyclosporin A (CsA) nephrotoxicity is associated with renal hypoxia and increases in free radicals in the urine. This study was designed to elucidate the mechanism of radical production caused by CsA. Pretreatment of rats with CsA (25 mg/kg, i.g.) for 5 days decreased glomerular filtration rates by 65%, an effect largely prevented by both dietary glycine (5%) or renal denervation. CsA dissolved in olive oil produced a 6-line alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN)/free radical signal in the urine, which partitioned predominantly into the aqueous phase after chloroform extraction (i.e., it is water soluble). Dimethyl sulfoxide (DMSO) is attacked by the hydroxyl radical to produce a methyl radical; administration of CsA with [(12)C]DMSO produced two radical species in urine, one with hyperfine coupling constants similar to the 4-POBN/methyl radical adduct found in aqueous solution. CsA given with [(13)C]DMSO produced a 12-line spectrum, confirming the formation of hydroxyl radicals. The methyl radical produced by the hydroxyl radical represented 62% of radicals detected in urine but only 15% in bile. Therefore, hydroxyl radicals are produced largely in the kidney. Free radicals in urine were increased about 5-fold by CsA, an effect completely blocked by the inhibitory neurotransmitter, glycine, or by renal denervation. CsA infusion for 30 min increased efferent renal nerve activity 2-fold, and dietary glycine (5%) totally blocked this phenomenon. Taken together, these data are consistent with the hypothesis that CsA increases hydroxyl radical formation by increasing renal nerve activity resulting in vasoconstriction and hypoxia-reoxygenation. Glycine blunts the effect of CsA on the renal nerve, which explains, in part, prevention of nephrotoxicity.

Animals↗
PubMed1998

Antiviral activity of a selective ribonucleotide reductase inhibitor against acyclovir-resistant herpes simplex virus type 1 in vivo.

The present study reports the activity of BILD 1633 SE against acyclovir (ACV)-resistant herpes simplex virus (HSV) infections in athymic nude (nu/nu) mice. BILD 1633 SE is a novel peptidomimetic inhibitor of HSV ribonucleotide reductase (RR). In vitro, it is more potent than ACV against several strains of wild-type as well as ACV-resistant HSV mutants. Its in vivo activity was tested against cutaneous viral infections in athymic nude mice infected with the ACV-resistant isolates HSV type 1 (HSV-1) dlsptk and PAAr5, which contain mutations in the viral thymidine kinase gene and the polymerase gene, respectively. Following cutaneous infection of athymic nude mice, both HSV-1 dlsptk and PAAr5 induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. A 10-day treatment regimen with ACV given topically four times a day as a 5% cream or orally at up to 5 mg/ml in drinking water was partially effective against HSV-1 PAAr5 infection with a reduction of the area under the concentration-time curve (AUC) of 34 to 48%. The effects of ACV against HSV-1 dlsptk infection were not significant when it was administered topically and were only marginal when it was given in drinking water. Treatment under identical conditions with 5% topical BILD 1633 SE significantly reduced the cutaneous lesions caused by both HSV-1 dlsptk and PAAr5 infections. The effect of BILD 1633 SE against HSV-1 PAAr5 infections was more prominent and was inoculum and dose dependent, with AUC reductions of 96 and 67% against infections with 10(6) and 10(7) PFU per inoculation site, respectively. BILD 1633 SE also significantly decreased the lesions caused by HSV-1 dlsptk infection (28 to 51% AUC reduction). Combination therapy with topical BILD 1633 SE (5%) and ACV in drinking water (5 mg/ml) produced an antiviral effect against HSV-1 dlsptk and PAAr5 infections that was more than the sum of the effects of both drugs. This is the first report that a selective HSV RR subunit association inhibitor can be effective against ACV-resistant HSV infections in vivo.

Acyclovir↗