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Biomedical subjects

J A Low

Publications and source records attributed to J A Low.

At least 19 recordsLinked to original sources

Specialist community palliative care services--a survey of general practitioners' experience in Eastern Sydney.

The role of the general practitioner (GP) in providing palliative care in the community is of increasing importance. Concomitantly, there is more interaction between the palliative care support services and the GP. Even when there is input from the palliative care support services, there can be barriers that impede effective delivery of palliative care by the GP. These include poor communication between the GP and the supporting team, inaccessibility of the service and inadequate after-hours coverage. We carried out a postal survey to assess what experiences and perceptions GPs working within the Eastern Sydney Area had of our palliative care support service. The response was generally favourable, with most GPs finding the level of communication, accessibility, usefulness of advice given and degree of follow-up visits by the service to be adequate. However, an important number felt that we tended to over-hospitalise our patients.

Community Health Services↗

Increased stromal expression of murine urokinase plasminogen activator in a human breast cancer xenograft model following treatment with the matrix metalloprotease inhibitor, batimastat.

The matrix metalloprotease (MMP) family of enzymes and the urokinase plasminogen activator (uPA) pathway have both been implicated in tumor invasion and metastasis and in poor prognosis of cancer. We have previously shown that treatment with batimastat, a synthetic MMP inhibitor, leads to significant retardation but not regression of tumor growth in a human breast cancer xenograft model. In addition, batimastat treatment did not inhibit local tumor invasion, nor did it encourage stromal encapsulation of the tumor, suggesting the additional involvement of non-MMP proteolytic mechanisms. To investigate the presence of an alternative extracellular matrix protease whose activity is known to be important in breast cancer, but which is not inhibited by batimastat, expression of murine and human uPA were examined by in situ hybridization and ELISA. No differences were observed between untreated and batimastat-treated tumors regarding human uPA mRNA and protein. In contrast, murine uPA mRNA expression was increased at the tumor-stromal junction in batimastat-treated tumors in comparison with the control tumors. In agreement with these results, batimastat treatment was shown to significantly induce murine uPA protein content in the tumors. Inoculating MDA435/LCC-6 cells into immunodeficient, uPA-deficient mice resulted in tumor growth retardation as compared to tumor growth in littermate wild-type controls, while addition of batimastat treatment to uPA-/- mice did not result in further growth inhibition. The increased expression of stromal uPA may represent a cellular response to MMP inhibition and may demonstrate a new level of plasticity in the malignant progression of the disease. These results may have important implications for the clinical applications of MMP inhibitors, as well as for development of other anti-invasion drugs.

Animals↗

The prediction and prevention of intrapartum fetal asphyxia in term pregnancies.

OBJECTIVE: This study was undertaken to examine the roles of clinical risk scoring, electronic fetal heart rate monitoring, and fetal blood gas and acid-base assessment in the prediction and prevention of intrapartum fetal asphyxia in term pregnancies. STUDY DESIGN: The outcomes of 166 term pregnancies with biochemically confirmed fetal asphyxia (umbilical artery base deficit at delivery, >12 mmol/L) were examined. This population included 83 pregnancies delivered abdominally matched with 83 pregnancies delivered vaginally. Antepartum and intrapartum clinical risk factors and neonatal complications were documented. Fetal assessments included fetal heart rate patterns in the fetal heart rate record and fetal capillary blood gas and acid-base assessments. Fetal asphyxia was classified as mild, moderate, or severe on the basis of umbilical artery base deficit (cutoff >12 mmol/L) and neonatal encephalopathy and other organ system complications. RESULTS: Fetal asphyxial exposures were as follows: mild, 140; moderate, 22; and severe, 4. Intervention and delivery during the first or second stage of labor occurred in 98 of the 166 pregnancies. Predictive fetal heart rate patterns were the primary indication leading to intervention and delivery during the first or second stage of labor. Clinical risk factors when present were secondary indications in the clinical decision to intervene. Fetal blood gas and acid-base assessment was a useful supplementary test in 41 pregnancies. Intervention and delivery may have prevented the progression of mild asphyxia in 78 pregnancies and may have modified the degree of moderate or severe asphyxia in 20 pregnancies. CONCLUSION: Although fetal heart rate patterns will not discriminate all asphyxial exposures, continuous fetal heart rate monitoring supplemented by fetal blood gas and acid-base assessment can be a useful fetal assessment paradigm for intrapartum fetal asphyxia. Such an assessment paradigm will not prevent all cases of moderate or severe fetal asphyxia. However, prediction and diagnosis with intervention and delivery during the first or second stage of labor could prevent the progression of mild asphyxia to moderate or severe asphyxia in some cases.

Acid-Base Imbalance↗

Role for the adenovirus IVa2 protein in packaging of viral DNA.

Although it has been demonstrated that the adenovirus IVa2 protein binds to the packaging domains on the viral chromosome and interacts with the viral L1 52/55-kDa protein, which is required for viral DNA packaging, there has been no direct evidence demonstrating that the IVa2 protein is involved in DNA packaging. To understand in greater detail the DNA packaging mechanisms of adenovirus, we have asked whether DNA packaging is serotype or subgroup specific. We found that Ad7 (subgroup B), Ad12 (subgroup A), and Ad17 (subgroup D) cannot complement the defect of an Ad5 (subgroup C) mutant, pm8001, which does not package its DNA due to a mutation in the L1 52/55-kDa gene. This indicates that the DNA packaging systems of different serotypes cannot interact productively with Ad5 DNA. Based on this, a chimeric virus containing the Ad7 genome except for the inverted terminal repeats and packaging sequence from Ad5 was constructed. This chimeric virus replicates its DNA and synthesizes Ad7 proteins, but it cannot package its DNA in 293 cells or 293 cells expressing the Ad5 L1 52/55-kDa protein. However, this chimeric virus packages its DNA in 293 cells expressing the Ad5 IVa2 protein. These results indicate that the IVa2 protein plays a role in viral DNA packaging and that its function is serotype specific. Since this chimeric virus cannot package its own DNA, but produces all the components for packaging Ad7 DNA, it may be a more suitable helper virus for the growth of Ad7 gutted vectors for gene transfer.

Adenoviridae↗

Maturation of fetal heart rate and body movement in 24-33-week-old fetuses threatening to deliver prematurely.

Maturation of spontaneous cardiac and body movement behavior from 24 to 33 weeks gestational age was characterized prospectively in 168 high-risk fetuses threatening to deliver prematurely. Forty-eight, low-risk fetuses delivering as healthy full-term infants served as a comparison group. Fetuses were classified on the basis of gestational age at time of testing and newborn outcome following delivery (high-risk: premature compromised, premature healthy, term healthy infant; low-risk term healthy). In the high-risk group, the average fetal heart rate was greater and decreased over gestation from 148 to 140 bpm, regardless of outcome. In the low-risk group, it decreased from 145 to 138 bpm. In high- and low-risk groups, the average number of heart rate accelerations greater than or = 15 bpm increased over gestation from 2-3 to 8 while the average number of maternally perceived movements decreased. It was concluded that maturational changes in spontaneous fetal heart rate and maternally perceived body movements in fetuses threatening to deliver prematurely parallel those of low-risk fetuses.

Analysis of Variance↗

End-of-life issues--preferences and choices of a group of elderly Chinese subjects attending a day care centre in Singapore.

INTRODUCTION: This was an exploratory study that was intended to provide a descriptive analysis of the choices and preferences of a group of elderly Chinese subjects attending a day care centre in Singapore with regard to end-of-life issues. MATERIALS AND METHODS: A semi-structured one-to-one interview was conducted to collect data from the subjects. Qualitative techniques were used to analyse the data. RESULTS: Forty-three subjects were interviewed. The median age was 71 years. There were more women than men (58.1% vs. 41.9%). The predominant religion was Buddhism/Taoism. 83.7% and 76.7% of the subjects preferred to be told of the diagnosis and prognosis of a terminal illness, respectively. The person most preferred to reveal the diagnosis was the attending doctor (60.5%). About 83.7% of the subjects have never heard of the Advanced Medical Directive Act, while 37.2% agreed that making an advanced directive would be necessary. Twenty-three (53.5%) would choose the doctor, while 15 (34.9%) would choose a family member as a surrogate decision-maker. Twenty-two (51.2%) thought that euthanasia should be allowed, while 15 (34.9%) disagreed. With regard to supportive measures at the end of life, 67.4% wanted cardiopulmonary resuscitation, 62.8% wanted artificial ventilation, 55.8% wanted nasogastric feeding, 65.1% wanted intravenous hydration and 41.9% wanted renal dialysis. CONCLUSION: There is a need for closer communication between older persons and their carers with regard to end-of-life care. The attending doctor appears to have an important role in this respect.

Advance Directives↗

A pitfall to avoid when starting a patient on transdermal fentanyl.

BACKGROUND: A woman with advanced carcinoma of the ovary developed fentanyl toxicity while being changed from oral morphine to transdermal fentanyl. OBJECTIVE: To explain the reason for the toxicity and ways to avoid it. DISCUSSION: The transdermal fentanyl patch is proving to be a safe, well tolerated and effective treatment modality in the control of cancer pain, but care has to be exercised when using this drug, especially at the time of initiation, as the consequences may be disastrous for the patient.

Administration, Cutaneous↗

Predictive value of electronic fetal monitoring for intrapartum fetal asphyxia with metabolic acidosis.

OBJECTIVE: To determine the predictive value of each fetal heart rate (FHR) variable and of patterns of FHR variables for fetal asphyxia during labor. METHODS: This matched case-control study included an asphyxia group of 71 term infants with umbilical artery base deficit greater than 16 mmol/L and a control group of 71 term infants with umbilical artery base deficit less than 8 mmol/L. Each FHR record available for the 4 hours before delivery was scored in 10-minute cycles for each FHR variable. Selected patterns of important FHR variables were examined during the last hour before delivery for their predictive value for fetal asphyxia. RESULTS: The FHR variables associated with fetal asphyxia included absent and minimal baseline variability and late and prolonged decelerations. Fetal heart rate patterns with absent baseline variability were the most specific but identified only 17% of the asphyxia group. The sensitivity of this test increased to 93% with the addition of less specific patterns. The estimated positive predictive value ranged from 18.1% to 2.6%, and the negative predictive value ranged from 98.3% to 99.5%. CONCLUSION: A narrow 1-hour window of FHR patterns including minimal baseline variability and late or prolonged decelerations will predict fetal asphyxial exposure before decompensation and newborn morbidity. Thus, with careful interpretation, predictive FHR patterns can be a useful screening test for fetal asphyxia. However, supplementary tests are required to confirm the diagnosis and to identify the large number of false-positive patterns to avoid unnecessary intervention.

Acidosis↗

Maturation of body and breathing movements in 24-33 week-old fetuses threatening to deliver prematurely.

Maturation of spontaneous fetal body and breathing movements of 24- to 33-week-old fetuses in 168 pregnancies threatening to deliver prematurely were examined on the basis of newborn outcome (premature compromised, premature healthy, term healthy). Maturation of fetuses in 60 low-risk pregnancies delivering as healthy full-term infants served as a normative comparison group. Each fetus was observed for 30 min; the amount of body and breathing movements were noted and an estimation of amniotic fluid volume was made. The pattern of behavioural maturation was similar for all outcome groups; with advancing gestation there was a decrease in body movements and an increase in breathing movements. Both reduced activity levels and advanced behaviours were observed in the high-risk outcome groups. The high-risk fetuses had reduced levels of body movements which increased with better outcome and, an earlier onset of increased amounts of breathing, occurring at 30 weeks in contrast to 33 weeks for the comparison group. In the presence of ruptured membranes, those high-risk fetuses who were born prematurely had less breathing compared to those who delivered at term. Similar maturation patterns among high- and low-risk outcome groups suggests normal/typical functional development in the high-risk fetal groups. The observed differential behaviours were associated with prematurity and most likely associated with events leading to premature labour.

Amniotic Fluid↗

Intrapartum Fetal Surveillance. Is It Worthwhile?

Potentially significant intrapartum fetal asphyxia occurs in approximately 20 per 1000 births. Moderate and severe fetal asphyxia exposure with newborn morbidity occurs in 3 to 4 1000 births, with brain damage and subsequent disability in at least 1 per 1000 births. Although the prevalence of moderate and severe asphyxia is modest, prevention is important because of the serious implications of this complication to the child, family, and society. Because of the limited predictive value of clinical risk factors, the interpretation of patterns in a fetal heart rate record has become the primary screening test for intrapartum fetal asphyxia. Despite extensive clinic experience and numerous clinical trials, the benefits of EFM as a screening test have not been established, and harm may occur owing to unnecessary intervention. This observation raises serious ethical issues. When an intervention is initiated by the clinician rather than the patient, the clinician under greater obligation to ensure that the benefits outweigh the harm. Several factors complicate the demonstration of benefits of EFM as a screening test. There is no consensus regarding a protocol of fetal surveillance for low-risk patient who account for approximately 25% of intrapartum fetal asphyxia. Moderate and severe asphyxia cannot be prevented when asphyxial exposure has occurred before labor or before the onset of fetal surveillance. Prediction of intrapartum fetal asphyxia cannot occur when the quality of the record does not permit interpretation. Interpretation of predictive fetal heart rate patterns cannot occur unless the record is consistently and carefully scored. Prediction of most cases of intrapartum fetal asphyxia on the basis of fetal heart rate patterns is possible but difficult. Because the goal of intrapartum fetal surveillance is the prevention of moderate and severe fetal asphyxia, prediction must be achieved before fetal decompensation. Prediction must occur before absent baseline fetal heart rate variability evident in the record, which is uniformly associated with cerebral dysfunction and, in some cases, brain damage. The possibility of fetal asphyxia must be considered when, within a 1-hour window of recording, there are two or more cycles of minimal baseline fetal heart rate variability and two or more cycles of late or prolonged decelerations or both. Because approximately 9 of 10 predictive fetal heart rate patterns are false-positive, supplementary tests to confirm the diagnosis and to identify false-positives to prevent unnecessary intervention are essential. Until such time as additional fetal assessment tests are validated, blood gas and acid-base assessment of fetal blood can provide a definitive diagnosis and identify false-positive predictions.

Cardiotocography↗

Is euthanasia compatible with palliative care?

There has been a gradual shift in the attitude of the medical community as well as the lay public towards greater acceptance of euthanasia as an option for care of the terminally ill and dying. There have also been calls by certain groups to actually legalize voluntary euthanasia and physician-assisted suicide for patients who meet certain conditions, some of which are as follows: that the patient be of a sound mind, suffering from an incurable or terminal illness, experiencing unbearable suffering and uncontrollable pain. The rationale for legalizing euthanasia is based on the principle of the patient's right of self-determination and the duty of doctors to relieve pain and suffering at all times. A few within the medical community quickly saw certain similarities in terms of goals and aims between euthanasia and palliative care and, thus, proposed that euthanasia be an option or choice for difficult palliative care cases. Some even went as far as to suggest that euthanasia and palliative care be part of the continuum of care for terminally ill patients. When palliative medicine fails to fully control pain and suffering for the patient, euthanasia can be the logical next step in the continuum of care. This article seeks to discuss why the rationale for legalizing euthanasia is flawed, why euthanasia goes against the fundamental principles of Medicine in general and why it is incompatible with the practice of palliative medicine.

Ethics, Medical↗

Ethnicity, obstructive sleep apnoea and ischaemic heart disease.

We studied the relationship between different ethnic groups, obstructive sleep apnoea (OSA) and ischaemic heart disease. Four hundred and thirty-two inpatients from the medical wards were interviewed. Limited overnight sleep studies were done in 129 of those who had habitual snoring, daytime sleepiness based on an Epworth sleepiness scale of 8 or more, or a large neck size of 40 cm or more. There were 315 Chinese (72.9%), 67 Malays (15.5%), 43 Indians (10%) and 3 from other races (1.4%). The prevalence of OSA was 19.7%, 30% and 12% among the Chinese, Malays and Indians, respectively. The prevalence ratio for OSA was 1.52 in Malays using Chinese patients as the baseline (P = 0.07). The median neck circumference was 37 cm in both racial groups. The median body mass index was 22.7 kg/m2 in Chinese compared to 23.6 kg/m2 in Malays. The median apnoea-hypopnoea index was 22.7, 19.0 and 26.9 events/hour among the Chinese, Malays and Indians, respectively. OSA was independently associated with the prevalence of IHD (adjusted prevalence ratio 1.68; 95% CI: 1.15, 2.46; P = 0.009). The prevalence of ischaemic heart disease (IHD) was 31%, 24% and 28% in Chinese, Malays and Indians, respectively. The prevalence ratio for IHD in Malays compared to Chinese was 0.77. After adjusting for OSA, there was an even greater reduction in the risk of IHD (adjusted prevalence ratio 0.70). This suggests that OSA is a confounder in the relationship between race and ischaemic heart disease.

Adult↗

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↗

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↗

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↗

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↗

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↗