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1.
S Afr Med J ; 107(10): 882-886, 2017 Sep 22.
Article in English | MEDLINE | ID: mdl-29022533

ABSTRACT

BACKGROUND: Namibia regards hepatitis B virus (HBV) infection as a public health problem and introduced hepatitis B vaccinations for infants during 2009. However, information on HBV infection in the country remains limited, and effective public health interventions may be compromised in the absence of adequate evidence-based data. Available data from the World Health Organization (WHO) estimate that 15 - 60% of the normal population in many African countries may be positive for one or more of the HBV serological markers. OBJECTIVE: To investigate the distribution of HBV infection in Namibia, using available laboratory data for 2013. METHODS: A cross-sectional descriptive study was conducted using pre-existing electronic laboratory data on HBV infection. The data were retrieved from the central Namibia Institute of Pathology laboratory in Windhoek during January - December 2013. Tests were done on the following three main groups: (i) pregnant women during routine antenatal care (ANC) visits; (ii) patients with HIV/AIDS during antiretroviral therapy clinic visits; and (iii) any other individual suspected of having HBV infection. RESULTS: Of a total of 77 238 hepatitis B surface antigen test results retrieved countrywide, 9 087 (11.8%) were positive. Of the positive results, 246/9 087 (2.7%) were in children aged 0 - 14 years, with the sexes equally affected. HBV infections increased markedly, particularly among females, in the age group 15 - 39 years, reaching a peak in the age group 30 - 34 years. Routine screening of pregnant women for HBV during ANC visits was found to be systematically conducted in only two regions, Ohangwena and Khomas. CONCLUSIONS: This study showed high proportions of positive results in pregnant women, patients with HIV/AIDS and individuals suspected of having HBV infection. The Ministry of Health and Social Services and stakeholders may wish to consider improving the routine and surveillance reporting systems for viral hepatitis and uptake of screening for pregnant women in all regions, and expanding HBV screening to other population groups. Population-based or similar studies are therefore required to determine the HBV prevalence and risk factors. This will assist Namibia in developing appropriate national viral hepatitis strategies as per WHO recommendations.

2.
Article in English | AIM (Africa) | ID: biblio-1271138

ABSTRACT

Background. Namibia regards hepatitis B virus (HBV) infection as a public health problem and introduced hepatitis B vaccinations for infants during 2009. However, information on HBV infection in the country remains limited, and effective public health interventions may be compromised in the absence of adequate evidence-based data. Available data from the World Health Organization (WHO) estimate that 15 - 60% of the normal population in many African countries may be positive for one or more of the HBV serological markers.Objective. To investigate the distribution of HBV infection in Namibia, using available laboratory data for 2013.Methods. A cross-sectional descriptive study was conducted using pre-existing electronic laboratory data on HBV infection. The data were retrieved from the central Namibia Institute of Pathology laboratory in Windhoek during January - December 2013. Tests were done on the following three main groups: (i) pregnant women during routine antenatal care (ANC) visits; (ii) patients with HIV/AIDS during antiretroviral therapy clinic visits; and (iii) any other individual suspected of having HBV infection.Results. Of a total of 77 238 hepatitis B surface antigen test results retrieved countrywide, 9 087 (11.8%) were positive. Of the positive results, 246/9 087 (2.7%) were in children aged 0 - 14 years, with the sexes equally affected. HBV infections increased markedly, particularly among females, in the age group 15 - 39 years, reaching a peak in the age group 30 - 34 years. Routine screening of pregnant women for HBV during ANC visits was found to be systematically conducted in only two regions, Ohangwena and Khomas.Conclusions. This study showed high proportions of positive results in pregnant women, patients with HIV/AIDS and individuals suspected of having HBV infection. The Ministry of Health and Social Services and stakeholders may wish to consider improving the routine and surveillance reporting systems for viral hepatitis and uptake of screening for pregnant women in all regions, and expanding HBV screening to other population groups. Population-based or similar studies are therefore required to determine the HBV prevalence and risk factors. This will assist Namibia in developing appropriate national viral hepatitis strategies as per WHO recommendations


Subject(s)
Hepatitis B virus , Namibia , Pregnant Women , Prenatal Care , Risk Factors
3.
Food Control ; 35(1): 260-266, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24882947

ABSTRACT

Reducing human Campylobacter cases has become a priority for the UK Government. However the public's views on acceptability of interventions to reduce Campylobacter in poultry production are poorly understood in the UK and in other countries around the world. The objective of the study was to investigate how increasing awareness and knowledge changes consumer acceptability of interventions that reduce human campylobacteriosis in the poultry food chain. This approach is readily applicable to other risks and associated interventions. It involved a survey of the views of consumers in the Grampian region in North East Scotland. This found that better hygiene practices on farm, freezing chicken meat and vaccination of chickens were acceptable to the majority of participants (95%, 53% & 52% respectively) whilst irradiation and chemical wash of chicken meat were acceptable to <50%. Increasing consumer awareness by providing information on the Campylobacter disease burden in humans increased the number of participants finding them acceptable. However, chemical wash and irradiation remained the least acceptable interventions, although highly effective at reducing Campylobacter, and were found to be never acceptable to >50% of respondents. It was found on average that food poisoning concern, previous awareness of Campylobacter and living in rural or urban areas had either no or little effect effect on the acceptability of interventions. Further, previous awareness of Campylobacter did not influence consumer concern of harmful bacteria on chicken meat. Overall, findings indicate that increasing consumer acceptability of the most effective interventions is likely to be a difficult process.

4.
J Perinatol ; 33(8): 581-5, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23538645

ABSTRACT

Members of the genus Cronobacter are an emerging group of opportunist Gram-negative pathogens. This genus was previously thought to be a single species, called Enterobacter sakazakii. Cronobacter spp. typically affect low-birth-weight neonates, causing life-threatening meningitis, sepsis and necrotizing enterocolitis. Outbreaks of disease have been associated with contaminated infant formula, although the primary environmental source remains elusive. Advanced understanding of these bacteria and better classification has been obtained by improved detection techniques and genomic analysis. Research has begun to characterize the virulence factors and pathogenic potential of Cronobacter. Investigations into sterilization techniques and protocols for minimizing the risk of contamination have been reviewed at national and international forums. In this review, we explore the clinical impact of Cronobacter neonatal and pediatric infections, discuss virulence and pathogenesis, and review prevention and treatment strategies.


Subject(s)
Cronobacter/pathogenicity , Enterobacteriaceae Infections/microbiology , Enterocolitis, Necrotizing/microbiology , Food Microbiology , Meningitis, Bacterial/microbiology , Sepsis/microbiology , Anti-Bacterial Agents/therapeutic use , Child , Enterobacteriaceae Infections/drug therapy , Humans , Infant , Infant Formula , Infant, Newborn , Opportunistic Infections/microbiology , Sterilization , Virulence Factors
5.
Epidemiol Infect ; 141(5): 976-86, 2013 May.
Article in English | MEDLINE | ID: mdl-22877359

ABSTRACT

A questionnaire survey was undertaken to determine the exposure of a study population to campylobacteriosis source risk factors (environmental, water, food) and results were stratified by age, population density and deprivation. Data were gathered using an exposure assessment carried out by telephone in the Grampian region of Scotland. Univariate analysis showed that children aged 5-14 years, living in low population density (0-44.4 persons/km2) and affluent areas had elevated exposure to environmental and water risk factors. Multivariate logistic regression analysis revealed that younger age groups and lower population density were significant indicators for most environmental risk factors. The results compared to reported disease incidence in Grampian showed that greater exposure to risk factors does not necessarily coincide with greater disease incidence for age groups, particularly for the 0-4 years age group. Further research is required to explain the relationship between exposure and disease incidence.


Subject(s)
Campylobacter Infections/epidemiology , Campylobacter Infections/microbiology , Campylobacter/isolation & purification , Adolescent , Adult , Aged , Animals , Child , Child, Preschool , Data Collection , Female , Food Microbiology , Humans , Infant , Male , Middle Aged , Population Density , Risk Factors , Scotland/epidemiology , Surveys and Questionnaires , Water Microbiology , Young Adult , Zoonoses
6.
Epidemiol Infect ; 140(8): 1414-29, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21943778

ABSTRACT

E. coli O157 can be transmitted to humans by three primary (foodborne, environmental, waterborne) and one secondary (person-to-person transmission) pathways. A regression model and quantitative microbiological risk assessments (QMRAs) were applied to determine the relative importance of the primary transmission pathways in NE Scotland. Both approaches indicated that waterborne infection was the least important but it was unclear whether food or the environment was the main source of infection. The QMRAs over-predicted the number of cases by a factor of 30 and this could be because all E. coli O157 strains may not be equally infective and/or the level of infectivity in the dose-response model was too high. The efficacy of potential risk mitigation strategies to reduce human exposure to E. coli O157 using QMRAs was simulated. Risk mitigation strategies focusing on food and environment are likely to have the biggest impact on infection figures.


Subject(s)
Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli O157/isolation & purification , Food Microbiology , Water Microbiology , Animals , Cattle , Feces/microbiology , Humans , Meat/microbiology , Risk Factors , Scotland/epidemiology , Sheep , Time Factors
7.
Philos Trans R Soc Lond B Biol Sci ; 366(1573): 1999-2009, 2011 Jul 12.
Article in English | MEDLINE | ID: mdl-21624920

ABSTRACT

Here, we bring together and contrast lay (accessible primarily through social science methodologies) and technical (via risk assessment and epidemiological techniques) views of the risk associated with the Escherichia coli O157 pathogen using two case study areas in the Grampian region of Scotland, and North Wales. Epidemiological risk factors of contact with farm animals, visiting farms or farm fields and having a private water supply were associated with postcode districts of higher than average disease incidence in the human population. However, this was not the case for the epidemiological risk factor of consumption of beef burgers, which was independent of disease incidence in the postcode district of residence. The proportion of the population expressing a high knowledge of E. coli O157 was greatest in high-incidence disease districts compared with low-incidence areas (17% cf. 7%). This supports the hypothesis that in high-disease-incidence areas, residents are regularly exposed to information about the disease through local cases, the media, local social networks, etc. or perhaps that individuals are more likely to be motivated to find out about it. However, no statistically significant difference was found between high- and low-incidence postcode districts in terms of the proportion of the population expressing a high likelihood of personal risk of infection (10% cf. 14%), giving a counterintuitive difference between the technical (epidemiological and quantitative microbiological risk assessment (QMRA)) and the lay assessment of E. coli O157 risk. This suggests that lay evaluations of E. coli O157 risk reflect intuitive and experience-based estimates of the risk rather than probabilistic estimates. A generally strong correspondence was found in terms of the rank order given to potential infection pathways, with environment and foodborne infection routes dominating when comparing public understanding with technical modelling results. Two general conclusions follow from the work. First, that integrative research incorporating both lay and technical views of risk is required in order that informed decisions can be made to handle or treat the risk by the groups concerned (e.g. the public, policy makers/risk managers, etc.). Second, when communicating risk, for example, through education programmes, it is important that this process is two-way with risk managers (e.g. including Food Standards Agency officials and communications team, public health infection control and environmental health officers) both sharing information with the public and stakeholder groups, as well as incorporating public knowledge, values and context (e.g. geographical location) into risk-management decisions.


Subject(s)
Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli O157/pathogenicity , Health Knowledge, Attitudes, Practice , Animals , Escherichia coli Infections/transmission , Feces/microbiology , Food Microbiology , Humans , Incidence , Risk Factors , Scotland/epidemiology , Soil Microbiology , Wales/epidemiology , Water Microbiology , Zoonoses
8.
Comput Methods Biomech Biomed Engin ; 14(12): 1071-7, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21424951

ABSTRACT

Lower back pain due to intervertebral disc (IVD) degeneration is a prevalent problem which drastically affects the quality of life of millions of sufferers. Healthy IVDs begin with high populations of notochordal cells in the nucleus pulposus, while by the second stage of degeneration, these cells will be replaced by chondrocyte-like cells. Because the IVD is avascular, these cells rely on passive diffusion of nutrients to survive. It is thought that this transition in cell phenotype causes the shift of the IVD's physical properties, which impede the flow of nutrients. Our computational model of the IVD illustrates its ability to simulate the evolving chemical and mechanical environments occurring during the early ageing process. We demonstrate that, due to the insufficient nutrient supply and accompanying changes in physical properties of the IVD, there was a resultant exponential decay in the number of notochordal cells over time.


Subject(s)
Aging/pathology , Intervertebral Disc Degeneration/physiopathology , Intervertebral Disc/physiopathology , Models, Biological , Notochord/physiopathology , Apoptosis , Computer Simulation , Humans , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/pathology , Notochord/pathology
9.
J Biomech Eng ; 132(4): 041004, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20387967

ABSTRACT

Identification of intervertebral disc (IVD) dynamics is important in understanding the spine mechanism and behavior. This paper experimentally identifies the dynamics of the bovine caudal IVD using experimental modal analysis and the inverse receptance coupling method. Experimental modal analysis was performed on free-free mounted bovine caudal vertebrae joined by an IVD and a fused IVD joint. Shear, rotational, and axial dynamics of the joints are identified by curve fitting of the frequency response functions, and identifying the damping ratio, stiffness, and modal frequency in each axis. The identified dynamics are compared with the IVD joints with and without fusion. Results provide important insight into IVD dynamics and fused IVD dynamics. This method can be extended to identify human IVD joint dynamics.


Subject(s)
Intervertebral Disc Displacement/physiopathology , Intervertebral Disc Displacement/surgery , Intervertebral Disc/physiopathology , Intervertebral Disc/surgery , Models, Biological , Spinal Fusion/methods , Animals , Compressive Strength , Computer Simulation , Humans , Range of Motion, Articular
10.
Am J Physiol Regul Integr Comp Physiol ; 298(3): R700-6, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20071614

ABSTRACT

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a critical response to perinatal hypoxia. Recent data show that adenosine appears to inhibit baseline levels of fetal cortisol and to restrict the increase in ACTH and cortisol during moderate hypoxia. Because adenosine increases substantially during profound asphyxia, it is possible, but untested, that counterintuitively it might restrict the HPA response to more severe insults. It is unclear which receptors mediate the effects of adenosine on the HPA axis; however, adenosine A(1) receptor activation is important for adaptation to hypoxia. We therefore investigated whether adenosine A(1) receptor blockade modulates ACTH and cortisol levels in fetal sheep at 118 to 126 days gestation, randomly allocated to receive an intravenous infusion of either vehicle (vehicle-occlusion, n = 7) or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, an A(1) receptor antagonist, DPCPX-occlusion, n = 7) infused 60 min before and during 10 min of umbilical cord occlusion, or infusion of DPCPX for 70 min without occlusion (DPCPX-sham, n = 6). Experiments were terminated after 72 h. Fetal ACTH levels increased significantly (P < 0.01) during occlusion, but not sham occlusion, and returned to baseline values by 60 min after occlusion. In the vehicle-occlusion group, fetal cortisol and cortisone plasma levels increased significantly (P < 0.05) 60 min after the occlusion and returned to baseline values by 24 h. In contrast, there was a marked increase in both fetal cortisol and cortisone during DPCPX infusion before occlusion to a level greater even than the maximum rise seen after occlusion alone. This increase was sustained after occlusion, with increased cortisol levels compared with occlusion alone up to 72 h. In conclusion, fetal cortisol concentrations are suppressed by adenosine A(1) receptor activity, largely though a direct adrenal mechanism. This suppression can be partially overcome by supraphysiological stimuli such as asphyxia.


Subject(s)
Asphyxia/physiopathology , Hypothalamo-Hypophyseal System/physiology , Pituitary-Adrenal System/physiology , Receptor, Adenosine A1/metabolism , Adenosine A1 Receptor Antagonists , Adrenocorticotropic Hormone/blood , Animals , Carbon Dioxide/blood , Female , Gestational Age , Hydrocortisone/blood , Oxygen/blood , Pregnancy , Sheep , Umbilical Cord , Xanthines/pharmacology
11.
J Perinatol ; 28 Suppl 1: S14-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18446170

ABSTRACT

INTRODUCTION: Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are neonatal intestinal emergencies that affect premature infants. Although most cases of early NEC can be successfully managed with medical therapy, prompt surgical intervention is often required for advanced or perforated NEC and FIP. METHODS: The surgical management and treatment of FIP and NEC are discussed on the basis of literature review and our personal experience. RESULTS: Surgical options are diverse, and include peritoneal drainage, laparotomy with diverting ostomy alone, laparotomy with intestinal resection and primary anastomosis or stoma creation, with or without second-look procedures. CONCLUSIONS: The optimal surgical therapy for FIP and NEC begins with prompt diagnosis and adequate fluid resuscitation. It appears that there is no significant difference in patient outcome based on surgical management alone. However, the infant's weight, comorbidities, surgeon preference and timing of intervention should be taken into account before operative intervention.


Subject(s)
Enterocolitis, Necrotizing/surgery , Evidence-Based Medicine , Infant, Premature, Diseases/surgery , Infant, Very Low Birth Weight , Intestinal Perforation/surgery , Professional Competence , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/mortality , Gestational Age , Humans , Infant, Newborn , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/mortality , Intestinal Perforation/diagnosis , Intestinal Perforation/mortality , Randomized Controlled Trials as Topic , Resuscitation , Survival Rate
12.
J Perinatol ; 28 Suppl 1: S9-S13, 2008 May.
Article in English | MEDLINE | ID: mdl-18446181

ABSTRACT

INTRODUCTION: Necrotizing enterocolitis (NEC) has been recognized for over 40 years as a cause of inflammation and necrosis of the small and large intestine of infants born at less than 36 weeks of gestation. NEC remains a significant health problem for infants born prematurely and may become the leading cause of morbidity and mortality among these infants worldwide. The sequence of events leading to NEC is complex and multifactorial, although damage to the intestinal epithelium and invasion by bacteria are known to play central roles in disease pathogenesis. STUDY DESIGN: Bacteria initiate a cascade of inflammation that may progress to intestinal necrosis and perforation with sepsis and death. RESULT: Treatment of infants at risk for NEC with probiotic bacteria may be an area of great potential, as probiotic bacteria may promote maturation of the epithelial barrier and function to exclude bacterial pathogens from critical niches in the intestine, thereby disrupting a primary pathway in disease pathogenesis. CONCLUSION: Understanding how probiotic bacteria, or other novel therapies, prevent or limit disease propagation in NEC will be paramount in limiting the impact of disease in a growing population of premature newborns.


Subject(s)
Enterocolitis, Necrotizing/prevention & control , Evidence-Based Medicine , Infant, Premature, Diseases/prevention & control , Probiotics/therapeutic use , Professional Competence , Anti-Bacterial Agents/therapeutic use , Diagnosis, Differential , Enterocolitis, Necrotizing/diagnostic imaging , Enterocolitis, Necrotizing/etiology , Humans , Infant, Newborn , Infant, Premature, Diseases/diagnostic imaging , Infant, Premature, Diseases/etiology , Intensive Care, Neonatal , Intestinal Perforation/diagnostic imaging , Intestinal Perforation/etiology , Intestinal Perforation/prevention & control , Radiography , Randomized Controlled Trials as Topic , Resuscitation
13.
Emerg Med J ; 23(3): 179-82, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16498152

ABSTRACT

INTRODUCTION: Lactic acidosis portends a poor prognosis in trauma, sepsis, and other shock states and is useful for triaging and resuscitating emergency department (ED) patients. The authors sought to determine whether the AG is a reliable screen for lactic acidosis when applied specifically in the ED setting. METHODS: The authors performed a retrospective cohort study over a seven month period. Subjects were all ED patients that had a serum lactate obtained. Sensitivity analyses of the AG for detecting presence of lactic acidosis were calculated for the traditional AG normal value (AG <12) and for the lower AG normal value when using newer ion selective electrode assays (AG <6). RESULTS: Serum lactate levels were ordered in the ED on 440 occasions. 137 samples were excluded by protocol. Using an AG cutoff of 12, the sensitivity for detecting lactic acidosis was 58.2%, specificity was 81.0%, and the negative predictive value was 89.7%. Using the AG cutoff of 6, the sensitivity was 93.2%, the specificity was 17.3%, and the negative predictive value was 91.8%. CONCLUSIONS: The traditional definition of AG >12 was insensitive for the presence of lactic acidosis. Using the revised AG of >6 is more sensitive but non-specific for lactic acidosis. The authors conclude that employing the AG as a screen for LA may be inappropriate in ED patients. Instead, they recommend ordering a serum lactate immediately upon suspicion of a shock state. A prospective study to confirm these findings is needed.


Subject(s)
Acidosis, Lactic/diagnosis , Anions/analysis , Lactic Acid/blood , Adult , Aged , Cohort Studies , Emergency Service, Hospital , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Sensitivity and Specificity
14.
J Physiol ; 572(Pt 1): 131-9, 2006 Apr 01.
Article in English | MEDLINE | ID: mdl-16484307

ABSTRACT

Secondary cerebral hypoperfusion is common following perinatal hypoxia-ischaemia. However, it remains unclear whether this represents a true failure to provide sufficient oxygen and nutrients to tissues, or whether it is simply a consequence of reduced cerebral metabolic demand. We therefore examined the hypothesis that cerebral oxygenation would be reduced during hypoperfusion after severe asphyxia, and further, that the greater neural injury associated with blockade of the adenosine A(1) receptor during the insult would be associated with greater hypoperfusion and deoxygenation. Sixteen near-term fetal sheep received either vehicle or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) for 1 h, followed by 10 min of severe asphyxia induced by complete occlusion of the umbilical cord. Infusions were discontinued at the end of the occlusion and data were analysed for the following 8 h. A transient, secondary fall in carotid artery blood flow and laser Doppler flow was seen from approximately 1-4 h after occlusion (P < 0.001), with no significant differences between vehicle and DPCPX. Changes in laser Doppler blood flow were highly correlated with carotid blood flow (r(2)= 0.81, P < 0.001). Cortical metabolism was suppressed, reaching a nadir 1 h after occlusion and then resolving. Cortical tissue P(O(2)) was significantly increased at 1, 2 and 3 h after occlusion compared to baseline, and inversely correlated with carotid blood flow (r(2)= 0.69, P < 0.001). In conclusion, contrary to our initial hypothesis, delayed posthypoxic hypoperfusion was associated with suppression of cerebral metabolism and increased tissue P(O(2)), and was not significantly affected by preceding adenosine A1 blockade. These data suggest that posthypoxic hypoperfusion is actively mediated and reflects suppressed cerebral metabolism.


Subject(s)
Brain/blood supply , Brain/metabolism , Fetal Hypoxia/metabolism , Oxygen/metabolism , Receptor, Adenosine A1/metabolism , Reperfusion Injury/embryology , Reperfusion Injury/metabolism , Animals , Cerebrovascular Circulation , Female , Hypoxia, Brain/embryology , Hypoxia, Brain/metabolism , Oxygen Consumption , Pregnancy , Sheep
15.
Am J Physiol Regul Integr Comp Physiol ; 286(3): R576-83, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14604846

ABSTRACT

Renal impairment is common in preterm infants, often after exposure to hypoxia/asphyxia or other circulatory disturbances. We examined the hypothesis that this association is mediated by reduced renal blood flow (RBF), using a model of asphyxia induced by complete umbilical cord occlusion for 25 min (n = 13) or sham occlusion (n = 6) in chronically instrumented preterm fetal sheep (104 days, term is 147 days). During asphyxia there was a significant fall in RBF and urine output (UO). After asphyxia, RBF transiently recovered, followed within 30 min by a secondary period of hypoperfusion (P < 0.05). This was mediated by increased renal vascular resistance (RVR, P < 0.05); arterial blood pressure was mildly increased in the first 24 h (P < 0.05). RBF relatively normalized between 3 and 24 h, but hypoperfusion developed again from 24 to 60 h (P < 0.05, analysis of covariance). UO significantly increased to a peak of 249% of baseline between 3 and 12 h (P < 0.05), with increased fractional excretion of sodium, peak 10.5 +/- 1.4 vs. 2.6 +/- 0.6% (P < 0.001). Creatinine clearance returned to normal after 2 h; there was a transient reduction at 48 h to 0.32 +/- 0.02 ml.min(-1).g(-1) (vs. 0.45 +/- 0.04, P < 0.05) corresponding with the time of maximal depression of RBF. No renal injury was seen on histological examination at 72 h. In conclusion, severe asphyxia in the preterm fetus was associated with evolving renal tubular dysfunction, as shown by transient polyuria and natriuresis. Despite a prolonged increase in RVR, there was only a modest effect on glomerular function.


Subject(s)
Animals, Newborn/physiology , Asphyxia/physiopathology , Fetus/physiopathology , Polyuria/physiopathology , Renal Circulation/physiology , Algorithms , Animals , Asphyxia/complications , Asphyxia/pathology , Atrial Natriuretic Factor/blood , Blood Pressure/physiology , Creatinine/blood , Female , Heart Rate, Fetal/physiology , Hemodynamics/physiology , Immunohistochemistry , Kidney/pathology , Kidney Function Tests , Kidney Glomerulus/physiology , Polyuria/etiology , Potassium/metabolism , Pregnancy , Renin/blood , Sheep , Sodium/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism
16.
Tissue Eng ; 9(4): 667-77, 2003 Aug.
Article in English | MEDLINE | ID: mdl-13678445

ABSTRACT

An understanding of developmental biology can provide useful insights into how different tissue-engineered repairs might be designed. During embryogenesis of the intervertebral disk, the cells of the notochord play a critical role in initiating tissue formation, and may be responsible for development of the nucleus pulposus. In some species, including humans, these notochordal cells may eventually be lost, either through apoptosis or terminal differentiation, and are replaced by chondrocyte-like cells. However, there is some evidence that the notochordal cells may persist in at least some humans. This review discusses some of the potential applications of notochordal cells in tissue engineering of the nucleus pulposus.


Subject(s)
Intervertebral Disc/cytology , Notochord/cytology , Tissue Engineering , Animals , Dogs , Humans , Stem Cells , Swine
17.
Cancer Res ; 60(18): 5237-43, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-11016653

ABSTRACT

Prostate-specific membrane antigen (PSMA) is a well-characterized cell surface antigen expressed by virtually all prostate cancers (PCas). PSMA has been successfully targeted in vivo with (111)In-labeled 7E11 monoclonal antibody (mAb; ProstaScint; Cytogen, Princeton, NJ), which binds to an intracellular epitope of PSMA. This work reports the in vitro characterization of three recently developed mAbs that bind the extracellular domain of PSMA (PSMAext). Murine mAbs J415, J533, J591, and 7E11 were radiolabeled with 131I and evaluated in competitive and saturation binding studies with substrates derived from LNCaP cells. J415 and J591 were conjugated to 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid labeled with (111)In. The uptake and cellular processing of these antibodies were evaluated in viable LNCaP cells. All four mAbs could be labeled with 131I up to a specific activity of 350 MBq/mg with no or little apparent loss of immunoreactivity. Competition assays revealed that J415 and J591 compete for binding to PSMAext antigen. J533 bound to a region close to the J591 binding epitope, but J533 did not interfere with J415 binding to PSMA. mAb 7E11 did not inhibit the binding of J415, J533, or J591 (or vice versa), consistent with earlier work that these latter mAbs bind PSMAext whereas 7E11 binds the intracellular domain of PSMA. Saturation binding studies demonstrated that J415 and J591 bound with a similar affinity (Kds 1.76 and 1.83 nM), whereas J533 had a lower affinity (Kd, 18 nM). In parallel studies, all four mAbs bound to a similar number of PSMA sites expressed by permeabilized cells (1,000,000-1,300,000 sites/cell). In parallel studies performed with viable LNCaP cells, J415, J533, and J591 bound to a similar number of PSMA sites (i.e., 600,000-800,000 sites/cell), whereas 7E11 bound only to a subpopulation of the available PSMA sites (95,000 sites/cell). This apparent binding of 7E11 to viable cells can be accounted for by a 5-7% subpopulation of permeabilized cells produced when the cells were trypsinized and suspended. Up to five DOTA chelates could be bound to either J415 or J591 without compromising immunoreactivity. A comparison of the cellular uptake and metabolic processing of the 131I- and (111)In-labeled antibodies showed a rapid elimination of 131I from the cell and a high retention of (111)In. All four mAbs recognized and bound to similar numbers of PSMAs expressed by ruptured LNCaP cells (i.e., the exposed intracellular and extracellular domains of PSMA). By comparison to J415 and J591, J533 had a lower binding affinity. Both J415 and J591 recognized and bound to the same high number of PSMAs expressed by intact LNCaP. By contrast, 7E11 bound to fewer sites expressed by intact LNCaP cells (i.e., the exposed extracellular domain of PSMA). Both J415 and J591 are promising mAbs for the targeting of viable PSMA-expressing tissue with diagnostic and therapeutic metallic radionuclides.


Subject(s)
Antibodies, Monoclonal/immunology , Antigens, Neoplasm/immunology , Antigens, Surface/immunology , Carboxypeptidases/immunology , Immunoconjugates/immunology , Iodine Radioisotopes , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/pharmacokinetics , Antibody Specificity , Antigens, Neoplasm/metabolism , Antigens, Surface/metabolism , Binding, Competitive , Carboxypeptidases/metabolism , Cell Membrane/metabolism , Chelating Agents/pharmacokinetics , Drug Stability , Glutamate Carboxypeptidase II , Humans , Immunoconjugates/metabolism , Immunoconjugates/pharmacokinetics , Indium Radioisotopes , Iodine Radioisotopes/therapeutic use , Isotope Labeling , Kinetics , Male , Prostatic Neoplasms/immunology , Prostatic Neoplasms/metabolism , Protein Structure, Tertiary , Quality Control , Tumor Cells, Cultured
18.
J Appl Physiol (1985) ; 89(3): 1065-71, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10956352

ABSTRACT

The purpose of this study was to devise a means to use laser-Doppler flowmetry to measure cerebral perfusion before birth. The method has not been used previously, largely because of intrauterine movement artifacts. To minimize movement artifacts, a probe holder was molded from epoxy putty to the contour of the fetal skull. A curved 18-gauge needle was embedded in the holder. At surgery, the holder, probe, and skull were fixed together with tissue glue. Residual signals were recorded after fetal death and after maternal death 1 h later. These averaged <5% of baseline flow signals, indicating minimal movement artifact. To test the usefulness of the method, cerebral flow responses were measured during moderate fetal hypoxia induced by giving the ewes approximately 10% oxygen in nitrogen to breathe. As fetal arterial PO(2) decreased from 21.1 +/- 0.5 to 10.7 +/- 0.4 Torr during a 30-min period, cerebral perfusion increased progressively to 56 +/- 8% above baseline. Perfusion then returned to baseline levels during a 30-min recovery period. These responses are quantitatively similar to those spot observations that have been recorded earlier using labeled microspheres. We conclude that cerebral perfusion can be successfully measured by using laser-Doppler flowmetry with the unanesthetized, chronically prepared fetal sheep as an experimental model. With this method, relative changes of perfusion from a small volume of the ovine fetal brain can be measured on a continuous basis, and movement artifacts can be reduced to 5% of measured flow values.


Subject(s)
Cerebrovascular Circulation , Fetus/physiology , Laser-Doppler Flowmetry/methods , Animals , Artifacts , Equipment Design , Fetal Hypoxia/physiopathology , Fetal Movement , Laser-Doppler Flowmetry/instrumentation , Sheep
19.
Keio J Med ; 49 Suppl 1: A58-60, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10750339

ABSTRACT

Laser Doppler flowmetry (LDF) has been used to measure flow in various organs of the adult, but has not been applied to the mammalian fetus. The purpose of this study was to apply LDF to measure cerebral blood flow of the fetal sheep and to assess the possible errors and artifacts of the method caused by myometrial, fetal, and maternal movements. By three days after probe placement, the flow signal had decreased 55% from initial post surgical readings and thereafter it became stable. During fetal hypoxia, the signal increased 48% and during hypercarbia it increased 59%. After fetal death, the signal decreased to 48% of control level. After maternal death, it decreased to 9% and electrical zero could not be reached. LDF is useful to measure changes of fetal cerebral microvascular perfusion because it can provide continuous signals but care is required in data handling and probe fixation when used for the mammalian fetus.


Subject(s)
Cerebrovascular Circulation , Fetus/blood supply , Animals , Female , Fetal Hypoxia/physiopathology , Hypercapnia/physiopathology , Hypothermia/physiopathology , Laser-Doppler Flowmetry , Microcirculation/physiology , Pregnancy , Sheep
20.
J Comp Physiol B ; 170(1): 1-10, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10707319

ABSTRACT

The respiratory physiology, heart rates and metabolic rates of two captive juvenile male harbour porpoises (both 28 kg) were measured using a rapid-response respiratory gas analysis system in the laboratory. Breath-hold durations in the laboratory (12 +/- 0.3 s, mean +/- SEM) were shorter than field observations, although a few breath-holds of over 40 s were recorded. The mean percentage time spent submerged was 89 +/- 0.4%. Relative to similarly-sized terrestrial mammals, the respiratory frequency was low (4.9 +/- 0.19 breaths.min-1) but with high tidal volumes (1.1 +/- 0.011), enabling a comparatively high minute rate of gas exchange. Oxygen consumption under these experimental conditions (247 +/- 13.8 ml O2.min-1) was 1.9-fold higher than predicted by standard scaling relations. These data together with an estimate of the total oxygen stores predicted an aerobic dive limit of 5.4 min. The peak end-tidal O2 values were related to the length of the previous breath-hold, demonstrating the increased oxygen uptake from the lung for the longer dives. Blood oxygen capacity was 23.5 +/- 1.0 ml.100 ml-1, and the oxygen affinity was high, enabling rapid oxygen loading during ventilation.


Subject(s)
Porpoises/physiology , Animals , Diving , Heart Rate/physiology , Oxygen/blood , Oxygen Consumption/physiology , Porpoises/blood , Pulmonary Gas Exchange , Respiration , Respiratory Function Tests
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