Biomedical subjects

J A Low

Publications and source records attributed to J A Low.

At least 37 records · Page 2Linked to original sources

PubMed1999

Posterior cerebral artery territory infarct presenting as acute psychosis.

An 82-year-old man with a past medical history of hypertension was admitted to a psychiatric hospital for sudden onset of acute psychosis. He was then transferred to an acute geriatric unit for further evaluation. During the admission the patient was noted to be very restless, agitated and noisy and was shouting and screaming incessantly. This was interspersed with occasional short periods of calm and quiet. Clinically, no obvious focal neurological deficits were detected. A CT scan of the brain was performed and it revealed an acute infarct involving the area supplied by the left posterior cerebral artery. This was a rather atypical presentation for an infarct involving this area.

Aged↗

PubMed1999

Phylogenetic signals from point mutations and polymorphic Alu insertions.

Allelic frequency data derived from five polymorphic Alu insertion loci and five point mutation polymorphic loci were compared to determine their ability to infer phylogenetic relationships among human populations. While point mutation polymorphisms inferred a monophyletic Caucasian clade that is corroborated by other studies, these data failed to support the generally accepted monophyly of Orientals with native Americans. In addition, there is less statistical bootstrap support for the maximum-likelihood tree derived from the point mutation polymorphisms as compared to those generated from either the Alu insertion data or the combined Alu insertion + point mutation data. The Alu data and the combined Alu insertion + point mutation data inferred a monophyletic relationship among the Oriental and native American populations. The Alu insertion data and the combined Alu insertion + point mutation data also displayed two separate, well defined, tight clusters of the Caucasian and the Oriental + native American populations which was not inferred from the point mutation data. These findings indicate greater phylogenetic information contained in Alu insertion frequencies than in allelic frequencies derived from point-mutations.

Alleles↗

PubMed1998

A descriptive study of the demography, symptomology, management and outcome of the first 300 patients admitted to an independent hospice in Singapore.

The aims of this study were: 1) to describe the demography, symptomology, investigations conducted, non-pharmacological interventions and outcome of patients admitted to an inpatient hospice and 2) to identify the nursing and medical needs of terminally ill patients. Case-notes of the first 300 patients admitted to Dover Park Hospice were studied retrospectively. There were 159 men and 141 women making up 325 admissions. The racial distribution was: Chinese 95.0%, Malays 3.0%, Indians 1.3% and Others 0.6%. Two-thirds of the men (64.2%) had spouses while 44.7% of the women were widowed. The mean age was 64.7 years. The 3 most common cancers were lung (21.7%), colorectal (14.6%) and hepatobiliary (12.5%). A proportion of patients (39.5%) were not known to have any metastases. Most patients were referred from hospitals and the home-care based Hospice Care Association. The commonest reason for admission was for "terminal care" (57.2%). At admission, only 38% of the patients were aware of their diagnoses and prognosis while 30% did not know either. The average length of stay was 25 days with 7.7% of patients having more than one admission. The most common symptoms were pain, anorexia, breathlessness, insomnia, constipation and dry skin. Non-pharmacological interventions ranged from manual evacuation of the rectum to transfers to tertiary hospitals for surgery and other more invasive interventions. Many patients also attended day-care activities (23.1%). Outcome of the 325 admissions were as follows: went home 20%, died in the hospice 73.2%, went home to die 4.9% and others 1.8%.

Adult↗

PubMed1998

Care of elderly patients with DNR orders in Singapore--a descriptive study.

OBJECTIVE: To describe the demographic profile of a cohort of elderly patients with a 'do-not-resuscitate' (DNR) order at death and to study the specific supportive measures instituted or withdrawn during the DNR period and those in force at the time of death. METHODS: The case notes of patients who died between October 1996 and March 1997 in the Department of Geriatrics, Alexandra Hospital were studied retrospectively by a single observer. RESULTS: Only 95 out of an eligible 102 patients' case notes could be retrieved. Seventy-two (75.8%) patients had a DNR status at death. The racial distribution was as follows: 90.3% Chinese, 5.6% Indians, 2.8% Malays and 1.4% Others while their pre-admission domicile were: own home 79.2%, nursing home 19.4% others 1.4%. Those bedbound constituted 48.6% of the cohort while 29.2% had dementia and 43.1% were totally dependent for their activities of daily living. The commonest cause of death was pneumonia while the average duration patients were on the DNR status was 5.1 days before death. The commonest measures instituted during DNR period were as follows: oxygen therapy (38.9%), nasogastric tube insertion and feeding (30.6% and 33.3% respectively), intravenous fluid administration (33.3%), blood investigations (33.3%), opioid use (33.3%) and antibiotic use (29.2%). Measures withdrawn were intravenous fluid administration (36.1%), hourly monitoring of parameters (22.2%), antibiotics (13.9%), high dependency care (12.5%) and nasogastric tube feeding (6.9%). CONCLUSION: The DNR status is decided late in the course of a patient's illness when he may have been too ill to partake in the decision making process. Even if a DNR status was ordered, a patient might still be subjected to CPR at death.

Aged↗

PubMed1997

Threshold of metabolic acidosis associated with newborn complications.

OBJECTIVE: Our purpose was to determine the threshold of metabolic acidosis at delivery associated with newborn complications. STUDY DESIGN: This study was a matched case-control study of 174 term newborn infants. Three groups defined by umbilical artery base deficit at birth were 4 to 8 mmol/L, 8 to 12 mmol/L, and 12 to 16 mmol/L. Newborn complications during the 5 days after birth were documented. A composite complication score defined the magnitude of all complications in each neonate. RESULTS: Moderate and severe newborn encephalopathy and respiratory complications and composite complication scores >3 were increased in the group with an umbilical artery base deficit of 12 to 16 mmol/L. Moderate or severe newborn complications occurred in 10% of newborns in the same group, whereas such complications occur in 40% of neonates with an umbilical artery base deficit >16 mmol/L at birth. CONCLUSION: The threshold of fetal metabolic acidosis at delivery when moderate or severe newborn complications may occur is in an umbilical artery base deficit of 12 mmol/L. Thereafter, increasing metabolic acidosis is associated with a progression of severity of newborn complications.

Acidosis↗

PubMed1997

Intrapartum fetal asphyxia: definition, diagnosis, and classification.

Evidence of a significant metabolic acidosis, an umbilical artery base deficit > 12 mmol/L, confirms that an asphyxial exposure has occurred. This is observed at delivery in approximately 2% of all pregnancies. Classification of the severity of the asphyxial exposure is difficult because the duration and nature of the exposure and the characteristics of the fetal cardiovascular response to the asphyxia in the affected fetus is usually not known. A classification is proposed in which the exposure to asphyxia is confirmed by a blood gas and acid-base assessment with evidence of a significant metabolic acidosis and the severity is defined by newborn encephalopathy and other organ system complications. Outstanding issues that may enhance this classification are identified.

Acid-Base Equilibrium↗

PubMed1997

Intrapartum fetal asphyxia and the occurrence of minor deficits in 4- to 8-year-old children.

Term newborn infants, 48 of whom had mild intrapartum fetal asphyxia, and 43 controls were assessed between 4 and 8 years of age for evidence of selective brain damage and minor deficits. Measures of motor and cognitive development were obtained at 4 and at 6 to 8 years of age. Memory tests, including the Alternation Test and determinations of Extended Digit Span, Spatial Memory, and Paired Associate Learning, were given annually between 4 and 8 years of age. Assessments of the family, child health, and child behaviour were obtained. There were no differences between the asphyxia and control groups for motor or cognitive development or the serial tests of memory. The two groups did not differ in regard to family characteristics, child health, or child behaviour. These findings indicate that term newborn infants exposed to mild intrapartum fetal asphyxia do not have minor motor and cognitive deficits later in childhood.

Acidosis↗

PubMed1996

Severe fetal asphyxia associated with neuropathology.

Studies of fetal monkeys and lambs have demonstrated the association between a single prolonged episode of severe fetal hypoxia and the occurrence of neurologic abnormality. This case represents a single episode of fetal hypoxia with severe metabolic acidosis at delivery accounting for neurologic abnormality on postmortem examination that closely parallels the results of experimental studies.

Acidosis↗

PubMed1996

Metabolic acidosis and fetal reserve.

Dr Bailey, Director of the National Institute of Neurological Diseases and Blindness, Bethesda, Maryland, introduced the 1956 symposium on 'Neurological and psychological deficits of asphyxia neonatorum' by saying. 'Medical research in regard to cerebral palsy and other neurological disabilities has been relatively neglected. For a truly comprehensive attack on this problem we must focus a sharper scientific search for greater knowledge of those adverse biological factors which operate in the perinatal period. The proper point of departure in such a search is through controlled animal observations, for which purpose monkeys are best suited' (Windle, 1958). Our understanding of the significance of asphyxia is built on the foundation of the laboratory research that has followed upon this initiative. Laboratory studies in fetal monkeys and fetal lambs have clearly demonstrated that the fetus can initially compensate for an asphyxial insult and protect the vital organs. However, if the hypoxaemia progresses to a severe metabolic acidosis and cardiovascular decompensation with hypotension, brain damage will occur. There is a growing body of clinical evidence that supports the contention that the human fetus responds in a similar manner. The varied nature of hypoxic and ischaemic insults has been well demonstrated in animal studies. Total anoxia and isolated cerebral ischaemia are uncommon events in the human fetus. The common insult, particularly during labour, is a degree of hypoxia present over a variable period of time. This is fortunate in that such insults are associated with a period of fetal compensation that may last several hours, during which time a diagnosis of a developing metabolic acidosis can be made. This is the clinician's window of opportunity, when a definitive diagnosis of an asphyxial insult can be made and if necessary intervention made before the threshold of decompensation has been reached. A consensus on the threshold of decompensation has yet to be achieved. However, there is a growing body of evidence that the threshold is in the range of an umbilical artery base deficit of 12-16 mmol/l. Since the aim of the obstetrician during labour is the prevention of asphyxial morbidity and mortality, the determination of this threshold is important to provide criteria for clinical action. A blood gas and acid-base assessment with the determination of a metabolic acidosis is the best measure of an asphyxial insult that may be of clinical significance. The definition of the threshold of metabolic acidosis requiring intervention will continue to be clarified with future clinical research. However, there are many factors that will influence the fetal response to an asphyxial insult, which may require that a range of threshold be acknowledged. The effect upon the fetus will be influenced by whether the asphyxial event is the first or the last of a series of asphyxial episodes, and the duration of the asphyxial episode. The characteristics of the fetus, i.e. maturity (pre-term versus term), and fetal growth small for gestational age (SGA) or appropriate for gestational age (AGA) may influence the fetal response to an asphyxial insult. Improved understanding of these issues will provide a better rationale for clinical management.

Acidosis↗

PubMed1996

The matrix metalloproteinase inhibitor batimastat (BB-94) retards human breast cancer solid tumor growth but not ascites formation in nude mice.

Matrix metalloproteinases (MMPs) are thought to play a significant role in tumor invasion and metastasis as well as angiogenesis. Batimastat, also known as BB-94, acts as an inhibitor of metalloproteinase activity by binding the zinc ion in the active site of MMPs. In our study, the hormone-independent MDA435/LCC6 human breast cancer cell line was used to seed solid tumors s.c. into the region of the mammary fat pad in athymic nude mice. Mice were treated with 50 mg/kg batimastat i.p. Tumor volume measurements showed a statistically significant decrease in tumor size between batimastat-treated and control animals. In contrast, we also used the same MDA435/LCC6 cell line to propagate a malignant ascites in nude mice, which yielded a very different response to batimastat. Batimastat, in previously published literature, had been shown to prolong the life of mice bearing ovarian ascites tumors. Treatment with batimastat in our ascites model produced no increase in survival or significant suppression of ascites formation. However, treated animals showed dramatic tumor cell consolidation and less dispersed ascites cells compared with control animals. Two potential targets of batimastat, gelatinase A and B (MMP-2 and -9, respectively), were examined in both tumor sites. These metalloproteinases were present in both solid tumor and ascites fluid and in both cases were host derived and not produced by the tumor. We conclude that batimastat may have different effects on tumor progression and growth depending on the site of tumor implantation.

Animals↗

PubMed1995

Limitations in the clinical prediction of intrapartum fetal asphyxia.

OBJECTIVE: Our purpose was to demonstrate the predictive value of clinical risk scoring and fetal assessment for intrapartum fetal asphyxia. STUDY DESIGN: Intrapartum fetal asphyxia was defined by an umbilical artery buffer base < 34 mmol/L. The predictive value of 20 antepartum and intrapartum risk factors was examined in 1909 consecutive pregnancies. The predictive value of clinical risk factors with periodic fetal assessment was examined in a second population of 100 consecutive pregnancies with biochemically determined intrapartum fetal asphyxia. RESULTS: The incidence of intrapartum was 2.3%. Two problems were apparent in these studies. A significant proportion of intrapartum fetal asphyxia occurred in pregnancies with no risk factors. The positive predictive value of clinical risk factors was low, 3%, resulting in a large number of false positives requiring clarification. CONCLUSION: Screening and fetal assessment methods must be improved to ensure the early recognition of intrapartum fetal asphyxia that may require intervention during labor to avoid morbidity and mortality.

Delivery, Obstetric↗

PubMed1995

Newborn complications after intrapartum asphyxia with metabolic acidosis in the preterm fetus.

OBJECTIVE: Our purpose was to determine the nature of the complications in preterm newborns after intrapartum fetal asphyxia with metabolic acidosis at delivery. STUDY DESIGN: Thirty-seven preterm fetuses with metabolic acidosis were matched with 37 preterm fetuses with normal blood gas measurements at delivery. A complication score expressed the magnitude of newborn complications during the 10 days after delivery. RESULTS: The mean complication score for the preterm newborns at 32 to 36 weeks in the asphyxia group, 9.6, was significantly greater than that for the control group, 3.1. Fetal asphyxia was associated with severe complications in all systems. The complication scores for the preterm newborns < 32 weeks in the asphyxia group were of the same order as the control group. This may be related in part to a short duration of the asphyxial insult. The Apgar score at 1 minute was a valuable predictor of newborn complications in both the asphyxia and control groups. CONCLUSIONS: Intrapartum fetal asphyxia with metabolic acidosis at delivery is an important factor in the occurrence of severe complications, particularly in the central nervous system, respiratory system, and kidney, of preterm newborns.

Acidosis↗

PubMed1995

Cerebral perfusion, metabolism, and outcome.

Factors contributing to brain damage and an adverse outcome are complex. Both severe hypoxia-ischemia and prolonged hypoxia of lesser severity may cause brain damage. Compromised cerebral perfusion leads to ischemia. Fetal brain damage may begin because of a redistribution rather than reduction of cerebral blood flow. Normal newborn cerebral blood flow is low; fetal asphyxia at birth causes delayed cerebral hyperperfusion in the neonate. The threshold of newborn cerebral blood flow that is associated with brain damage has not yet been established. Hypoxia-ischemia will disrupt cerebral metabolism. The fetus can compensate for hypoxia up to a point; however, decompensation will occur when acidosis becomes severe. Normal newborn cerebral oxygen consumption is low compared with that in the adult; however, asphyxia, causing brain damage, is associated with abnormal newborn cerebral metabolism. Supplementary glucose may have a protective effect in the newborn brain. Hypoxia-ischemia will cause brain damage in the human fetus and neonate. There is a threshold of fetal asphyxia at birth when brain damage may occur. Sustained neonatal hypotension and hypoxemia are associated with brain damage and an adverse outcome.

Animals↗

PubMed1995

Validity of newborn oscillometric blood pressure.

The objective of this study was to determine the validity of oscillometric blood pressure in relation to arterial blood pressure. Thirty-one newborns were studied. Clinical characteristics, complications, and treatment interventions were documented. Arterial pressure (every 2 sec) and oscillometric pressure (every 3 min) were concurrently recorded for 1-2 h. Serial observations of oscillometric pressure followed the trend of arterial pressure in the individual newborn. However, the study averaged oscillometric pressures were lower than the arterial pressures: systolic, by 1 mmHg; mean, by 5.3 mmHg (p < 0.0001); and diastolic, by 4.6 mmHg (p < 0.0001). The variance of individual, 15-min averaged, and 1-h averaged observations of oscillometric pressure in relation to arterial pressure was examined. Variance for individual observations may be large. The least variance of oscillometric pressure was in the 1-h averaged mean pressure, in which the difference was +/- 2 mmHg in 77% and +/- 4 mmHg in 95% of observations. Clinical characteristics, with the exception of birth weight and treatment interventions, did not affect the variance of oscillometric pressure. This study implies that the offset in relation to arterial pressure should be established for each oscillometric pressure monitoring system. Hourly averaged mean oscillometric pressure is satisfactory for many newborn assessments and management circumstances. However, arterial pressure may be necessary to accurately document transient hypertension or hypotension or an unstable blood pressure.

Birth Weight↗

PubMed1994

Newborn complications after intrapartum asphyxia with metabolic acidosis in the term fetus.

OBJECTIVES: Our purpose was to determine the newborn complications after respiratory or metabolic acidosis at delivery and to demonstrate the characteristics of an asphyxial insult predictive of these complications. STUDY DESIGN: Fifty-nine term fetuses with metabolic acidosis were matched with 59 fetuses with normal blood gas measures at delivery. Fifty-one fetuses with respiratory acidosis were also examined. A complication score expressed the magnitude of newborn complications during the 10 days after delivery. RESULTS: Newborn complications were not increased after respiratory acidosis. Newborn complications after metabolic acidosis increase in frequency and severity with the increasing severity and duration of the metabolic acidosis. Thirty-two of the 59 newborns in the metabolic acidosis group had a high complication score. The index values predictive of high scores were the duration of the metabolic acidosis and the Apgar score at 1 minute. CONCLUSIONS: Intrapartum fetal asphyxia with a severe metabolic acidosis accounts for complications in all newborn systems. The probability of a high complication score increases from 14% with favorable index values to 85% with unfavorable index values.

Acidosis↗

PubMed1994

Cerebral blood flow velocity in term newborns following intrapartum fetal asphyxia.

Twenty-six term newborns with intrapartum fetal asphyxia, determined biochemically (umbilical artery base deficit > 12 mmol/l), were compared with 59 normal newborns to determine the effect of intrapartum fetal asphyxia on newborn blood pressure and cerebral blood flow velocity following delivery. Cerebral blood flow velocity observations with concurrent measures of blood pressure and heart rate were obtained during the 24 h after delivery and after 24 h. After delivery, diastolic blood pressure in the newborns of the asphyxia group was significantly greater than that of the newborns of the normal group and this difference persisted after 24 h. Cerebral blood flow velocity in the newborns of the asphyxia group was of the same order as that of the newborns of the normal group during the 24 h after delivery. However, there was a significant increase in both peak systolic and end-diastolic blood flow velocity after 24 h. The duration of metabolic acidosis may be a factor in the occurrence of this delayed cerebral blood flow velocity response. Observations of cerebral blood flow velocity should be continued for more than 24 h following delivery to determine the effect of intrapartum fetal asphyxia.

Asphyxia Neonatorum↗

PubMed1993

The relationship of asphyxia in the mature fetus to long-term neurologic function.

Asphyxia may occur before or during labor in the preterm or term fetus. The development of neuropathologic lesions depends on the degree and duration of the asphyxia. Anoxia may occur, but because of the short duration of the fetal response, it usually will cause the death of the fetus. The common mechanism leading to neuropathologic lesions in the fetus is a significant degree of hypoxia present for a particular period of time. Antepartum asphyxia will cause such lesions and deficits in children. What is missing are measures to establish the prevalence of antepartum asphyxia in a large population and the epidemiologic studies to determine the association between the asphyxia so documented and the deficits in surviving children. The prevalence of intrapartum fetal asphyxia is of the order of 2%. Most of these children will have no evidence of brain damage. The key is the fetal cardiovascular compensatory response that maintains cerebral blood flow and oxygen metabolism. This compensatory phase, subject to the severity of the hypoxia, may continue for several hours. In the clinical setting during labor, this provides the "window of opportunity" when a specific blood gas and acid-base diagnosis can be made, and with appropriate intervention, brain damage can be avoided. However, if the hypoxia persists, a threshold will be reached when fetal cardiovascular decompensation will occur. The compromised cerebral oxygen metabolism will result in brain damage and deficits in the children who survive. The threshold at which brain damage may occur is when the acidosis is severe (pH, < 7.0). At this time, systemic hypotension may occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Asphyxia Neonatorum↗

PubMed1993

The association between preterm newborn hypotension and hypoxemia and outcome during the first year.

Ninety-eight newborn infants, less than 34 weeks at birth, were studied to examine the relationship between newborn hypotension and hypoxemia and brain damage. Heart rate, blood pressure and oxygen tension were recorded continuously during the 96 h following delivery. Outcome measures included neuropathology in children who died, and motor and cognitive development at one year corrected age in children who survived. There were 22 children with a minor and 27 with a major abnormal outcome. There was a relationship between newborn hypotension, newborn hypoxemia and low birth weight, and a major abnormal outcome. The probability of a major abnormal outcome increased from 8% in newborns with no hypotension or hypoxemia, to 53% in children with both hypotension and hypoxemia. These findings support the contention that combinations of sustained newborn hypotension and hypoxemia are important factors in the development of brain damage, accounting for a major abnormal outcome.

Acidosis↗