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Biomedical subjects

C P Lee

Publications and source records attributed to C P Lee.

At least 19 recordsLinked to original sources
PubMed2002

Factors affecting outcomes of prenatally-diagnosed tumours.

OBJECTIVE: The outcomes of prenatally-diagnosed tumours affect obstetrical management and parental decisions. The present study reviews the factors affecting outcomes for fetuses with prenatally-diagnosed tumours. METHODS: Medical records of all fetuses referred to our institutions with antenatally-diagnosed tumours were reviewed for the type and location of the tumours, results of treatment and/or causes of death. RESULTS: From January 1994 to May 2001, there were 15 fetuses with antenatally- diagnosed tumours: mesoblastic nephroma (MN) (n=2); neuroblastoma (NB) (n=2); cystic hygroma (CH) (n=3); intracranial germ cell tumour (IGCT) (n=2); sacrococcygeal teratoma (SCT) (n=3) and haemangioma (liver, n=2; limb, n=1). One mother had termination of pregnancy for her fetal SCT. Three mothers had Caesarean section for large fetal heads (CH, n=2; IGCT, n=1). Three fetuses died; two with IGCT and one with SCT, who died of heart failure. Two newborns with CH needed emergency intubation and, later, one of them had tracheostomy. One baby had cardiac failure resulting from a lower limb haemangioma and needed drug therapy. All solid tumours (MN, NB, SCT) of the live births had no recurrence after surgery with or without adjuvant chemotherapy. CONCLUSION: Prenatally-diagnosed tumours without any other associated abnormality cause morbidity and mortality because of their location and vascularity. Solid tumours are relatively benign.

Adult↗
PubMed2001

Appearance of shortened Bcl-2 and Bax proteins and lack of evidence for apoptosis in rat forebrain after severe experimental traumatic brain injury.

To investigate whether apoptosis plays a role in traumatic brain injury (TBI), we examined the expression of Bcl-2 and Bax proteins and the release of mitochondrial cytochrome c in rat brains using Western blot analysis. Bcl-2 at the predicted 26 kDa was not detected in controls and TBI groups. However, at 1 h post-TBI, a shortened Bcl-2 protein with a molecular size of approximately 14.5 kDa was detected in the injured hemisphere (R). At 4 and 12 h post TBI, an additional bcl-2 band ( approximately 10 kDa) was detected in R. Both bands disappeared at 14 days post-injury. The predicted 21-kDa band of Bax was detected in both controls and TBI animals. In addition, two shortened Bax proteins ( approximately 18 kDa) were detected after TBI. The time course of appearance was similar to that of Bcl-2 described above. In the present study, neither cytochrome c release from mitochondria nor DNA fragmentation was detected in the forebrains of sham and TBI groups. Treatment of animals with an antioxidant N-acetylcysteine administered ip greatly diminished the levels of shortened Bcl-2 and Bax proteins. These findings suggest that the induction of shortened Bcl-2 and Bax proteins in rat brains may be associated with reactive oxygen species generated after TBI.

Acetylcysteine↗
PubMed2001

Azepanone-based inhibitors of human and rat cathepsin K.

The synthesis, in vitro activities, and pharmacokinetics of a series of azepanone-based inhibitors of the cysteine protease cathepsin K (EC 3.4.22.38) are described. These compounds show improved configurational stability of the C-4 diastereomeric center relative to the previously published five- and six-membered ring ketone-based inhibitor series. Studies in this series have led to the identification of 20, a potent, selective inhibitor of human cathepsin K (K(i) = 0.16 nM) as well as 24, a potent inhibitor of both human (K(i) = 0.0048 nM) and rat (K(i,app) = 4.8 nM) cathepsin K. Small-molecule X-ray crystallographic analysis of 20 established the C-4 S stereochemistry as being critical for potent inhibition and that unbound 20 adopted the expected equatorial conformation for the C-4 substituent. Molecular modeling studies predicted the higher energy axial orientation at C-4 of 20 when bound within the active site of cathepsin K, a feature subsequently confirmed by X-ray crystallography. Pharmacokinetic studies in the rat show 20 to be 42% orally bioavailable. Comparison of the transport of the cyclic and acyclic analogues through CaCo-2 cells suggests that oral bioavailability of the acyclic derivatives is limited by a P-glycoprotein-mediated efflux mechanism. It is concluded that the introduction of a conformational constraint has served the dual purpose of increasing inhibitor potency by locking in a bioactive conformation as well as locking out available conformations which may serve as substrates for enzyme systems that limit oral bioavailability.

Administration, Oral↗
PubMed2001

In vivo magnetic resonance (MR) study of fatty liver: importance of intracellular ultrastructural alteration for MR tissue parameters change.

Fatty liver is thought to have a shorter T1 relaxation time than normal liver tissue, due to the accumulation of triglyceride. Previous studies regarding T1 and T2 relaxation times, however, show widely different results. In order to elucidate the mechanism responsible for the changes and diversity of relaxation times in fatty liver, we created two animal models in 14 rabbits, one acute form (N = 6) and the other chronic form (N = 8). Four rabbits were taken as a control group. Tissue relaxation times and the magnetization transfer (MT) effect of the liver tissue in these two models were measured. The results were correlated with biochemical analysis of water and fat content and histological examination, including findings in light microscopy and electron microscopy. Although the fatty ratio in both forms of fatty liver was similar, their tissue relaxation rate and MT effect were significantly different. The acute form showed prolongation of both T1 and T2 relaxation times (512 +/- 51 msec vs. 710 +/- 95 msec and 39 +/- 1.8 msec vs. 48 +/- 3.7 msec, respectively) and a decrease of the MT effect (50 +/- 5.1% vs. 38 +/- 6.3%), compared to those of the control group and preinduction liver. The chronic form showed shorter T1 and T2 values (526 +/- 36 msec vs. 406 +/- 56 msec and 36 +/- 1.6 msec vs. 33 +/- 2.3 msec, respectively) and a stronger MT effect (21 +/- 0.9% vs. 26 +/- 2.3%). In acute form fatty liver, electron microscopic examination revealed dramatic subcellular changes, such as vesicular transformation, a markedly increased amount of smooth endoplasmic reticulum (SER), and disruption of the crista. These changes were not found in the chronic form fatty liver. From this study, we concluded that the ultrastructural alteration in the subcellular organelles of hepatocyte might play a crucial role for the chameleonic presentation of MR tissue parameters in fatty liver.

Animals↗
PubMed2001

The effect of fetal gender on nuchal translucency at 10-14 weeks of gestation.

Recent data have suggested that fetal nuchal translucency (NT) is affected by fetal gender. We investigated the size of this effect in 12 189 unselected pregnancies with known normal outcomes that had undergone NT measurements between 10 and 14 weeks of gestation. NT increased with gestation and was converted to multiples of the median (MoM) for the gestational day. The median NT MoM (95% CI) for female fetuses was 0.98 (0.97-0.99). This was significantly lower than that of the male fetuses (1.03; range 1.02-1.04) (p<0.0005; Wilcoxon rank-sum test). The gender difference was not observed at 10 weeks but was observed from 11 weeks onwards. There is no obvious explanation for the above findings.

Adult↗
PubMed2001

Universal antenatal human immunodeficiency virus testing in Hong Kong: consensus statement.

Following the recommendations of the Advisory Council on AIDS, Hong Kong, the Hospital Authority announced plans to introduce universal antenatal screening for human immunodeficiency virus infection and hence, a consensus conference was held to discuss strategies for implementing such screening in Hong Kong. This paper reports the discussions of the consensus conference. The consensus meeting group consisted of 15 clinicians and scientists from Hong Kong, Macau, and Thailand. Seven commonly asked questions concerning mother-to-child transmission of human immunodeficiency virus were selected for discussion by the participating panellists. Information on the laboratory diagnosis of human immunodeficiency virus infection and the efficacy of preventive measures in reducing mother-to-child transmission of human immunodeficiency virus were reviewed. Data from local studies was also presented and discussed. The timing, potential problems, and cost issues involved in testing all pregnant women in Hong Kong for human immunodeficiency virus were then considered.

Adult↗
PubMed2000

Acceptability of serum screening as an alternative to cytogenetic diagnosis of down syndrome among women 35 years or older in Hong Kong.

The addition of second trimester serum markers to maternal age increases the efficacy of screening for Down syndrome by maternal age alone. Among women aged 35 years or older, serum screening makes a large proportion of amniocentesis unnecessary. However, there are ethical and medicolegal concerns about serum screening in 'old' women, largely because some of the pregnancies affected by Down syndrome and other chromosomal abnormalities may not be detected. We investigated the acceptability of serum screening in women aged 35 years or older when it was offered as an alternative to prenatal cytogenetic diagnosis after detailed counselling. Women referred for prenatal diagnosis of Down syndrome because of advanced maternal age were given the options of cytogenetic diagnosis by chorionic villus sampling (CVS) or amniocentesis. As an alternative, they could choose to undergo second trimester serum human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) screening first before deciding on whether to undergo amniocentesis. Between January 1997 and October 1999, 3419 subjects were recruited. 1807 women (52. 9%) chose to undergo serum screening, 1516 women (44.3%) chose to have amniocentesis and 96 women chose to have CVS (2.8%). The proportion of women who chose serum screening rose steadily from 38. 8% in the year of 1997 to 63.4% in 1999. Significantly fewer Chinese women chose serum screening than non-Chinese. The decision as to whether to undergo an invasive diagnostic procedure or to be content with the relatively safer but less accurate screening test varies, being affected by the women's background and culture.

Adult↗
PubMed2000

Thermocoagulation for selective reduction of conjoined twins at 12 weeks of gestation.

Conjoined twins occur rarely. Most of the prenatally diagnosed cases are terminated either because of extensive organ sharing or because of the presence of major structural abnormalities. We present a case of omphalopagus conjoined twins diagnosed at 10 weeks of gestation with selective reduction performed at 12 weeks. The twins were conjoined at the umbilicus with vascular communication demonstrated at the conjunction. Twin A was normal but twin B was growth restricted and hydropic. Thermocoagulation of twin B was performed at 12 weeks by passing an insulated electric wire through a 18-gauge needle placed close to the fetal heart. Reassessment at 15 weeks showed that twin A was growing normally with a small dead twin B attached at its umbilicus. Twin B was subsequently sloughed off from this attachment and could be seen lying free in the amniotic cavity at 17 weeks. Twin A was delivered at term and was healthy. A small scar could be seen just above the umbilical cord insertion. This case represents the first antenatal example of selective reduction of conjoined twins by thermocoagulation.

Adult↗
PubMed2000

Impaired cerebral mitochondrial function after traumatic brain injury in humans.

OBJECT: Oxygen supply to the brain is often insufficient after traumatic brain injury (TBI), and this results in decreased energy production (adenosine triphosphate [ATP]) with consequent neuronal cell death. It is obviously important to restore oxygen delivery after TBI; however, increasing oxygen delivery alone may not improve ATP production if the patient's mitochondria (the source of ATP) are impaired. Traumatic brain injury has been shown to impair mitochondrial function in animals; however, no human studies have been previously reported. METHODS: Using tissue fractionation procedures, living mitochondria derived from therapeutically removed brain tissue were analyzed in 16 patients with head injury (Glasgow Coma Scale Scores 3-14) and two patients without head injury. Results revealed that in head-injured patients mitochondrial function was impaired, with subsequent decreased ATP production. CONCLUSIONS: Decreased oxygen metabolism due to mitochondrial dysfunction must be taken into account when clinically defining ischemia and interpreting oxygen measurements such as jugular venous oxygen saturation, arteriovenous difference in oxygen content, direct tissue oxygen tension, and cerebral blood oxygen content determined using near-infrared spectroscopy. Restoring mitochondrial function might be as important as maintaining oxygen delivery.

Adolescent↗
PubMed2000

Improvement in mitochondrial dysfunction as a new surrogate efficiency measure for preclinical trials: dose-response and time-window profiles for administration of the calcium channel blocker Ziconotide in experimental brain injury.

OBJECT: Determining the efficacy of a drug used in experimental traumatic brain injury (TBI) requires the use of one or more outcome measures such as decreased mortality or fewer neurological and neuropsychological deficits. Unfortunately, outcomes in these test batteries have a fairly large variability, requiring relatively large sample sizes, and administration of the tests themselves is also very time consuming. The authors previously demonstrated that experimental TBI and human TBI induce mitochondrial dysfunction. Because mitochondrial dysfunction is easy to assess compared with neurobehavioral endpoints, it might prove useful as an outcome measure to establish therapeutic time windows and dose-response curves in preclinical drug testing. This idea was tested in a model of TBI in rats. METHODS: Animals treated with the selective N-type voltage-sensitive calcium channel blocker Ziconotide (also known as SNX-111 and CI-1009) after cortical impact displayed significant improvement in brain mitochondrial function. When a single intravenous bolus injection of 4 mg/kg Ziconotide was given at different time intervals, ranging from 15 minutes before injury to 10 hours after injury, mitochondrial function was improved at all time points, but more so between 2 and 6 hours postinjury. The authors evaluated the effects on mitochondrial function of Ziconotide at different doses by administering 0.5 to 6 mg/kg as a single bolus injection 4 hours after injury, and found 4 mg/kg to be the optimum dose. CONCLUSIONS: The authors established these time-window profiles and dose-response curves on the basis of mitochondrial outcome measures in a total of 42 rats because there were such low standard deviations in these tests. Establishing similar time-window profiles and dose-response curves by using neurobehavioral endpoints would have required using 114 rats in much more elaborate experiments.

Animals↗
PubMed2000

Coexistent insulin dependent diabetes mellitus and hyperthyroidism in a patient with Down's syndrome.

The prevalence of thyroid disease is increased in Down's syndrome. Compared with adults, thyroid dysfunction in children with Down's syndrome is less frequently reported. Insulin dependent diabetes mellitus is also uncommon in Down's syndrome children. Coexistent insulin dependent diabetes mellitus and hyperthyroidism in Down's syndrome was only reported once previously in literature. We report an 8-year-old girl with Down's syndrome that had polyuria, polydipsia, abdominal pain and urinary incontinence one and half a month prior to admission. Physical examination revealed typical face of Mongolism and tachycardia. Thyroid glands were not palpable. Laboratory data revealed diabetic ketoacidosis with plasma glucose: 860 mg/dl. She had thyroid hyperfunction with TSH: < 0.1 microU/ml, T3: 219.7 ng/dl, T4: 15 micrograms/dl. Thyroid autoimmune antibodies were also increased. There was markedly increased radiotracer uptake in the bilateral thyroid glands in Tc-99 thyroid scan. We suggest that Down's syndrome children with insulin dependent diabetes mellitus should be evaluated carefully for thyroid function and autoimmune disease.

Child↗
PubMed1999

Prenatal ultrasonographic prediction of homozygous type 1 alpha-thalassemia at 12 to 13 weeks of gestation.

We determined the feasibility of prenatal prediction of type 1 homozygous alpha-thalassemia at 12 to 13 weeks of gestation by either abdominal or vaginal (or both) ultrasonographic examination to measure the fetal cardiothoracic ratio in 135 at-risk pregnancies. Forty-three fetuses were affected by homozygous type 1 alpha-thalassemia. The mean cardiothoracic ratio was significantly larger than that of the unaffected fetuses (0.54 vs 0.45, P <.0005), with no overlap between the 2 groups. A cardiothoracic ratio cutoff point of >/=0.5 was 100% sensitive and specific for disease.

Feasibility Studies↗
PubMed1999

Prediction of the intestinal absorption of endothelin receptor antagonists using three theoretical methods of increasing complexity.

PURPOSE: Three new computational strategies have been evaluated for their ability to predict intestinal membrane permeability to a series of endothelin receptor antagonists. METHODS: The three methods were evaluated using a set of ten nonpeptide endothelin receptor antagonists. The simplest method, "the rule of five", is based on 2D parameters such as the number of potential hydrogen bonds, molecular weight and calculated lipophilicity. A method based on molecular mechanics calculations is used to calculate 3D parameters such as polar and non-polar parts of the molecular surface area. The third method uses quantum mechanics to calculate molecular properties related to the valence region. RESULTS: Descriptors derived by the latter two methods correlated well with permeability coefficients of the endothelin receptor antagonists. On the other hand, the rule of five failed to discriminate between drugs with high and low permeability. CONCLUSIONS: Molecular surface descriptors and descriptors derived from quantum mechanics are potentially useful for the virtual screening of the permeability of the intestinal membrane to endothelin receptor antagonists.

Animals↗
PubMed1999

Cardiac blood flow studies in fetuses with homozygous alpha-thalassemia-1 at 12-13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 develop anemia as early as the first trimester. Our objective was to study hemodynamic indices in affected fetuses at 12-13 weeks of gestation to determine whether these would be useful in the prediction of anemia. DESIGN: Prospective observational study. SUBJECTS: Women referred before 14 weeks of gestation for the prenatal diagnosis of homozygous alpha-thalassemia-1. METHODS: Transabdominal and/or transvaginal Doppler sonography was performed to measure the flow velocities in the fetal ascending aorta and pulmonary artery at 12-13 weeks. The Doppler indices were compared between those that were subsequently confirmed to be affected by homozygous alpha-thalassemia-1 and those that were unaffected. RESULTS: Between June 1997 and April 1998, 60 eligible women were recruited. Doppler examination was successful in 58 fetuses. Of these, 22 were subsequently confirmed to be affected by homozygous alpha-thalassemia-1. The diagnosis was made by chorionic villus sampling and DNA analysis in two affected fetuses and by cordocentesis and hemoglobin evaluation in 20 affected fetuses. Hemoglobin concentrations could be measured in ten fetuses and these ranged from 4 to 8 g/dl. The affected fetuses had significantly higher peak velocities at the pulmonary valve and ascending aorta and a larger inner diameter of the pulmonary valve than that in unaffected fetuses. The total cardiac output was increased by one-third in affected fetuses and was mainly due to an increase of the right-side cardiac output. CONCLUSION: In the early stage of anemia, the fetus responds mainly by increasing its right-side cardiac output. However, there is extensive overlap of the values of cardiac output between the affected and the unaffected fetuses, precluding its use in the prediction of anemia.

Adult↗
PubMed1999

Prenatal sonographic features of spondylocostal dysostosis and diaphragmatic hernia in the first trimester.

Spondylocostal dysostosis is a congenital disorder characterized by multiple malformations of the vertebrae and ribs. We describe the sonographic features of an affected fetus at 12 and 14 weeks of gestation. The fetus had thoracic scoliosis, multiple vertebral and rib malformations and a grossly dilated stomach that had herniated into the chest through a left-sided diaphragmatic hernia. The stomach spanned the whole length of the fetal trunk.

Adult↗
PubMed1999

Nuchal translucency in fetuses affected by homozygous alpha-thalassemia-1 at 12-13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 are anemic in the first trimester. We studied their nuchal translucency (NT) measurements at 12-13 weeks of gestation. METHODS: Nuchal translucency was measured prospectively in fetuses at risk of homozygous alpha-thalassemia-1. Measurements of those fetuses subsequently confirmed to be affected by homozygous alpha-thalassemia-1 but with a normal karyotype were compared to those of 440 controls. The controls were from the general obstetric population who had NT measurements at 12 or 13 weeks with known normal outcome. All the NT measurements were expressed as multiples of the median (MoM) for the gestational day. RESULTS: Between 1996 and 1998, 94 at-risk pregnancies were studied. Of these, 32 were subsequently confirmed to be affected by homozygous alpha-thalassemia-1. Chromosome study was not carried out in three cases and these were excluded from the analysis. Nuchal translucency MoMs for cases and controls were found to fit a log Gaussian distribution. The log means (standard deviation) for case and control NT MoM were 0.075 (0.156) and -0.0019 (0.091), respectively. The median NT MoM (95% CI) for cases was 1.19 (1.08-1.62) and was significantly higher than that of the controls (p < 0.001). However, there was extensive overlap of NT between cases and controls. CONCLUSION: Overall, there was a 19% increase in NT MoM in fetuses affected by homozygous alpha-thalassemia-1. This represents a difference of only 0.3-0.4 mm, which is clinically insignificant. This finding indirectly suggests that the increased NT in trisomic fetuses cannot be explained by fetal anemia. Conversely, the presence of increased NT in a fetus at risk of homozygous alpha-thalassemia-1 should alert one to the possibility of chromosomal abnormality rather than being attributed to fetal anemia.

Adolescent↗