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Biomedical subjects

W W Lee

Publications and source records attributed to W W Lee.

At least 37 records · Page 2Linked to original sources
PubMed1996

A recent case of congenital malaria in Singapore.

We report a case of congenital malaria in a 2-month-old baby girl, born in Singapore of a Singaporean mother, who presented with fever for one week, gross hepatosplenomegaly and anaemia (haemoglobin 5.6 g/dL) and thrombocytopenia. Peripheral blood films showed Plasmodium vivax. There was no local transmission at that time, but the mother had spent the first 6 months of her pregnancy in Pakistan, where she had been treated for prolonged fever at 4 months amenorrhoea with ibuprofen alone. The mother and 2 siblings were asymptomatic and repeatedly tested negative on blood films for malaria parasites, but the mother tested positive for antibodies to Plasmodium on the Fluorescent Antibody Test. The child was treated with oral chloroquine and made an uneventful recovery. We postulate that this is believed to be the first recent case of congenital malaria in Singapore since it was declared malaria free in 1982. The diagnosis should be considered in babies of mothers who have travelled to places where malaria is endemic, as maternal infection may be unrecognised, and the child may be asymptomatic at birth.

Antimalarials↗
PubMed1995

A study of the test-retest reliability of ten olfactory tests.

Ten tests of olfactory function (including tests of odor identification, detection, discrimination, memory, and suprathreshold odor intensity and pleasantness perception) were administered on two test occasions to 57 subjects ranging in age from 18 to 83 years. The stability of the average test scores was determined across the two test sessions for 14 measures derived from these 10 tests and for subcomponents of the Japanese T&T olfactometer threshold test. In addition, the test-retest reliability (Pearson r) of each test measure was established. With the exception of a response bias measure, the average test scores did not differ significantly across the two test sessions. Statistically, the reliability coefficients of the primary test measures fell into three general classes bound by the following r values: 0.43-0.53; 0.67-0.71; 0.76-0.90. Detection threshold values were more reliable than recognition threshold values; those based upon a single ascending presentation series were much less reliable than those based upon a staircase procedure. The relationship between test length and reliability was examined for several of the tests and mathematically modeled. For example, within the staircase series incorporating the odorant phenyl ethyl alcohol, reliability was related (R2 = 0.984) to the number of reversals included in the threshold estimate by a function derived from the Spearman-Brown formula; namely, reliability = 0.455* # reversals/[1 + 0.455 (# reversals - 1)]. Reversal location, per se, had little influence on reliability. Overall, this study suggests that (i) considerable variation is present in the reliability of olfactory tests, (ii) reliability is a function of test length, and (iii) caution is warranted in comparing results from nominally different olfactory tests in applied settings since the findings may, in some instances, simply reflect the differential reliability of the tests.

Adolescent↗
PubMed1995

The auditory brain stem response in patients with brain stem or cochlear pathology.

OBJECTIVE: The purpose of this study was to determine the value, based on true-positive and false-positive rates, of various auditory brain stem response (ABR) indices in discriminating patients with brain stem lesions from patients with cochlear lesions. DESIGN: A factorial design was used in this retrospective study. Receiver operating characteristics (ROC) curves were constructed to analyze the performance of 32 patients with brain stem lesions and 33 patients with cochlear involvement for the absolute latency of wave V; the I-III, III-V, and I-V interwave intervals; the interaural latency difference and the V/I amplitude ratio. Analyzed in the same manner were four combinations of ABR indices. RESULTS: Based on the ROC curves, the clinically most valuable index was the I-V interval, but overall the individual indices showed only moderate sensitivity to brain stem pathology. By combining several indices, the sensitivity to brain stem involvement was improved. However, as expected, the overall false-positive rate also increased. CONCLUSIONS: There is a diagnostic advantage to using more than one ABR index in evaluating patients suspected of having brain stem involvement.

Adolescent↗
PubMed1995

Spirometry in the Lung Health Study: II. Determinants of short-term intraindividual variability.

The Lung Health Study (LHS) is a randomized clinical trial designed to determine whether a smoking intervention program and use of an inhaled bronchodilator (BD) can reduce the rate of decline of FEV1 in cigarette smokers with airflow limitation. During recruitment, spirometry was performed at second and third screening visits, a mean of 21 d apart. A total of 5,887 smokers, 35 to 60 yr of age and of whom 63% were men, met the study eligibility requirements. Smokers taking physician-prescribed BDs or with an FEV1 < 50% or > 90% predicted were excluded, as were those whose FEV1/FVC ratio was greater than 70%. Two inhalations of isoproterenol were given to determine BD response during the second visit. A serial dilution methacholine challenge test was done during the third visit to determine nonspecific airway reactivity. Ninety-five percent of the differences between FEV1 measured at the two visits were within 240 ml for women and within 320 ml for men (coefficients of repeatability). The best independent predictors of the mean short-term (between visit) intraindividual FEV1 variability were factors indicating intrinsic airway reactivity of the participants: bronchodilator response, methacholine reactivity, and the presence of wheezing; as well as factors influenced by the quality of spirometry testing: the difference between the highest and second highest FEV1s and peak flows during baseline spirometry, and the time to reach peak flow (PEFT).

Adult↗
PubMed1994

Gender difference in airway hyperresponsiveness in smokers with mild COPD. The Lung Health Study.

Methacholine bronchoprovocation challenge testing was successfully completed in 5,662 participants (3,556 men and 2,106 women) at the time they were randomized into the Lung Health Study, a multicenter trial designed to evaluate early intervention in chronic obstructive pulmonary disease (COPD). All participants were smokers between the ages of 35 and 60 yr who had mild COPD. The male:female prevalence of a positive challenge (PC20FEV1) was 25%:48% and 63%:87% at a PC20FEV1 of < or = 5 mg/ml (AHR5) and < or = 25 mg/ml (AHR25), respectively. This analysis explores these marked gender differences in airway hyperresponsiveness (AHR). Relative risks (RR) for predictors of AHR and the 95% confidence intervals (95% CI) were estimated using semiparametric Cox proportional-hazards models. The initial model controlled for age, gender, smoking history, height, and weight. The RR (95% CI) for female gender was 1.75 (1.60, 1.92). When the measured baseline FEV1 was added to the model as a surrogate for airway caliber, the RR for female gender decreased to 1.06 (0.96, 1.18). Thus, in this population of middle-aged smokers with mild COPD, the high prevalence of AHR appears to be associated with a decrease in airway caliber. The higher prevalence of AHR noted in women is due to their having a smaller airway caliber than their male counterparts.

Adult↗
PubMed1994

Categorization response time with multidimensional stimuli.

Categorization response time (RT) was examined in three separate experiments, in each of which exemplars varied on two physical dimensions. Three different types of stimuli were used: (1) horizontal and vertical line segments of varying length that were joined at an upper left corner, (2) rectangles of varying width and height, and (3) circles or semicircles of varying size with a radial arm of varying orientation. No evidence was found that stimulus familiarity or the category prototypes played any special role in determining categorization RT. Instead, RT decreased with distance from the stimulus to the categorization decision bound.

Decision Making↗
PubMed1992

The lung health study: airway responsiveness to inhaled methacholine in smokers with mild to moderate airflow limitation. The Lung Health Study Research Group.

As part of a multicenter clinical trial (Lung Health Study), methacholine inhalation challenge testing was performed in 5,877 current cigarette smokers, ages 35 to 59 yr (mean 48.5 +/- 6.8 yr), with borderline to moderate airflow limitation (FEV1/FVC ratio 63.0 +/- 5.5). The test was successfully completed in 96.4% of subjects, of whom 63% were male and 95.9% were white. Symptomatic reactions to methacholine were rarely severe enough to require evaluation by a trial physician. Nonspecific airways hyperresponsiveness (AHR) was defined as a greater than or equal to 20% decline in FEV1 from the post-diluent control value after inhalation of less than or equal to 25 mg/ml methacholine. AHR was noted in a significantly higher percentage of women (85.1%) than men (58.9%). Moreover, nearly twice as many women as men (46.6 and 23.9%, respectively) responded to less than or equal to 5 mg/ml of methacholine. In both men and women, baseline degree of airways obstruction and clinical center were strongly associated with AHR (p less than 0.001), whereas age was not. Additional associations with AHR were analyzed in men and women separately using logistic regression after adjustment for baseline lung function, age, and center-to-center differences. In men, AHR was significantly related to symptoms of wheeze, chronic cough and/or sputum, and a history of asthma or hay fever (p less than 0.004), but not to current or lifetime tobacco use. By contrast, among women, AHR was not significantly associated with chronic cough and/or phlegm (p greater than 0.05) or a past history of asthma or hay fever (p greater than 0.1) and was only weakly related to wheeze and current asthma (p = 0.04), as well as to cigarette pack-years (p = 0.044). These results indicate that most continuing smokers with functional evidence of early chronic obstructive pulmonary disease have nonspecific AHR that is strongly related to gender and baseline lung function and, to a lesser extent, to respiratory symptoms. The reason for the striking effect of gender on AHR in early chronic obstructive pulmonary disease is unclear but cannot be attributed to male-female differences in age, cigarette use, presence of asthma, or baseline degree of airflow obstruction.

Adult↗
PubMed1992

Enterogenous cyst of the fourth ventricle: case report.

The authors present an intracranial enterogenous cyst of the fourth ventricle in a Chinese woman having symptoms of headache, dizziness and vertigo for approximately six months. A computerized tomography study of the brain disclosed a low density lesion within the fourth ventricle. A cystic tumor was completely removed and a histopathological examination diagnosed it is an enterogenous cyst; a rare lesion. During the post-operative follow-up, her symptoms gradually resolved and she was free of complaints within two years.

Brain Diseases↗
PubMed1991

Predicting similarity and categorization from identification.

In this article, the relation between the identification, similarity judgment, and categorization of multidimensional perceptual stimuli is studied. The theoretical analysis focused on general recognition theory (GRT), which is a multidimensional generalization of signal detection theory. In one application, 2 Ss first identified a set of confusable stimuli and then made judgments of their pairwise similarity. The second application was to Nosofsky's (1985b, 1986) identification-categorization experiment. In both applications, a GRT model accounted for the identification data better than Luce's (1963) biased-choice model. The identification results were then used to predict performance in the similarity judgment and categorization conditions. The GRT identification model accurately predicted the similarity judgments under the assumption that Ss allocated attention to the 2 stimulus dimensions differently in the 2 tasks. The categorization data were predicted successfully without appealing to the notion of selective attention. Instead, a simpler GRT model that emphasized the different decision rules used in identification and categorization was adequate.

Adult↗
PubMed1991

Structure-activity relationships for tumour radiosensitization by analogues of nicotinamide and benzamide.

Nicotinamide has been shown in our laboratory and those of other investigators to be an effective radiosensitizer of a variety of mouse tumours, while producing little or no radiosensitization of normal tissues. Its mechanism of action is different from classical electron-affinic compounds and appears to be the result of improved tumour oxygenation. In this study we have synthesized 29 analogues of nicotinamide and benzamide and characterized them for their tumour radiosensitization and acute toxicity in mice. The data show that a wide range of additions to the nicotinamide and benzamide ring produce tumour radiosensitization similar to that produced by equimolar doses of misonidazole, but that substitutions of the amide tend to reduce radiosensitization. Other structure-activity relationships are evident. Although some compounds produce similar tumour radiosensitization to nicotinamide at equimolar doses, and are comparably low in acute toxicity, none appears sufficiently superior to supplant nicotinamide itself as a candidate for clinical trials. Thus these data provide evidence that nicotinamide, because of the extensive experience with its use in man, is likely to be the best drug in the benzamide-nicotinamide series for development as a radiosensitizer of human tumours.

Animals↗
PubMed1990

Estimation of the coefficient of variation from laboratory analysis of split specimens for quality control in clinical trials.

An explicit statistical model is proposed for the coefficient of variation for laboratory analyses of constituents of blood, serum, saliva, or other specimens. A method for computing the maximum likelihood estimate of the key parameter is described, and compared with two simpler noniterative estimates. Validity of the model is explored by analysis of data from the central laboratory of a large cooperative clinical trial. Simulation studies are employed to compare the accuracy of the three estimators of the coefficient of variation. For most laboratory measurements for which the model is valid, one of the two noniterative estimates is nearly as accurate and unbiased as the maximum likelihood estimate.

Clinical Trials as Topic↗
PubMed1989

Structure-activity relationships for benzotriazine di-N-oxides.

SR 4233 (3-amino-1,2,4-benzotriazine 1,4-dioxide) is a bioreductive agent that selectively kills and radiosensitizes hypoxic mammalian cells in vitro and murine tumors in vivo. In an attempt to better understand the mechanism of action of the drug, and to determine whether a superior analog may exist, 15 benzotriazine-di-N-oxide analogs of SR 4233 have been evaluated to date for the following properties: hypoxic and aerobic toxicity toward CHO cells in vitro, drug-induced stimulation of oxygen consumption by incubation with respiration-inhibited cells, and acute LD50 evaluated in BALB/c mice. We noted several correlations between these biological properties of the drugs and some of their physicochemical characteristics. Both the hypoxic cytotoxicity and stimulation of oxygen consumption by respiration-inhibited cells were positively correlated with E1/2, the polarographic half-wave reduction potential, and a measure of electron affinity. The air-to-nitrogen differential cytotoxicity reached a maximum (corresponding to SR 4233) and then declined with increasing E1/2. The acute LD50 of each analog in mice decreased with increasing E1/2. One new compound, SR 4482, was found to be more toxic to hypoxic cells in vitro, but less toxic to mice, than SR 4233. It is similar in structure to SR 4233, but lacks any substituent in the 3-position of the triazine ring. This promising drug may represent a member of a new subseries of 1,2,4-benzotriazines with different structure-activity relationships.

Animals↗
PubMed1986

Preferential tumor radiosensitization by analogs of nicotinamide and benzamide.

The effects of a range of different analogs of nicotinamide and benzamide on the X ray response of the EMT-6 tumor in vivo was investigated. Using an in vivo/in vitro survival assay, sensitization was seen at a dose of 2 mmole/kg for all but one of the analogs tested. The enhancement ratios (ER's) ranged from 1.0 to 1.5. Of particular interest were nicotinamide and SR-4350 which gave large ER's (1.5 and 1.4 respectively) at doses which were only about 12% of the LD50 values. In one normal tissue studied (skin reaction) a large single dose of nicotinamide (8 mmole/kg) only gave an ER of 1.1. These results will be discussed with reference to the mechanisms involved and the clinical implications.

Animals↗
PubMed1986

Radiosensitization by diamide analogs and arsenicals.

Several analogs of the glutathione (GSH) oxidizing reagent diamide [diazenedicarboxylic acid bis(N,N'-diethylamide)] were tested as radiosensitizers of aerobic cells. In general, radiosensitization correlates with the rate of reaction with cellular reducing agents and occurs only when the reductive capacity of the cell is exceeded. SR-4077, [diazenedicarboxylic acid bis(N,N-piperidide)], is particularly suitable for mechanistic studies, because it is less cytotoxic than diamide, but is equally reactive toward cellular GSH. SR-4077 sensitizes CHO cells to X rays under aerobic conditions, even when the drug is added after irradiation. Radiosensitization is expressed both as a change in the exponential slope of the radiation cell survival curve and as a decrease in the shoulder of the survival curve. Phenylarsine oxide, a dithiol-binding reagent, sensitizes aerobic CHO cells to X rays by modification of the shoulder of the survival curve. The results are consistent with the hypothesis that the shoulder-modifying effect of GSH oxidants is caused by the loss of protein thiols, which might be involved in the repair of X ray-induced DNA damage.

Animals↗
PubMed1986

SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells.

We have examined the effects of the benzotriazine di-N-oxide SR-4233 (3-amino-1,2,4-benzotriazine-1,4 dioxide) on a variety of aerobic and hypoxic cells in culture, and on tumors in mice. The cell lines used were Chinese hamster ovary (HA-1), mouse 10T1/2, RIF-1, and SCC VII cells, and the human cell lines HCT-8, AG1522, and A549. The effect of SR 4233 in combination with irradiation was also examined in the SCC VII tumor growing in the flank of C3H mice using clonogenic assay (tumors excised 24 hr after irradiation). We found SR-4233 to be a potent and selective killer of hypoxic cells. Cell killing as a function of time for the various cell lines was exponential, with no shoulder. Drug concentrations producing equivalent levels of cell killing were 75-200 fold lower in hypoxic than in aerobic cells for the mouse and hamster lines, and 15-50 fold lower for the human cells. In vivo experiments showed that the non-toxic dose of 0.3 mmole/kg of SR-4233 enhanced radiation-induced tumor cell kill when the drug was given between 1 hr before and 2 hr after the radiation dose. We have also shown that the drug metabolizes more rapidly under hypoxic than aerobic conditions, both in vitro and in vivo. The toxic product(s) is unknown, but could be the 1-electron reduction product, the radical anion, because the mono N-oxide (the 2-electron reduction product) did not display cytotoxicity or selective killing under hypoxic conditions. This compound could therefore be a useful tool in tumor biology, as well as being a new lead in the development of bioreductive cytotoxic agents for cancer therapy.

Animals↗
PubMed1983

Misonidazole neurotoxicity in mice decreased by administration with pyridoxine.

A series of toxicological and pharmacological experiments was performed to test the hypothesis that alterations of pyridoxine (Vitamin B6) metabolism may play an important role in the development of misonidazole (MISO) neurotoxicity. The formation of a Schiff's base between the final reduction product of MISO, 2-amino MISO (NH2-MISO), and pyridoxal-HCl in ethanol was demonstrated. Mice receiving daily intraperitoneal injections of MISO suffered significantly less toxicity (as determined by survival, weight gain and neurological tests) when large doses of pyridoxine-HCl (PYR) were delivered concomitantly, and consequently were able to tolerate administration of more than twice as many MISO injections. PYR did not alter the pharmacokinetics of MISO, either when given simultaneously or when given by multiple repeated daily injections prior to MISO. The administration of PYR also did not alter the radiosensitization by MISO in an in vivo-in vitro cloning assay with the EMT6 tumor in BALB/c mice. If depletion or altered metabolism of pyridoxine by reduced metabolites is also responsible for the neurotoxic effects of nitroimidazoles in humans, then concomitant administration of pyridoxine (in doses greater than the molar quantity of NH2-MISO formed) should inhibit the development of such symptoms and allow administration of larger doses of MISO than are currently clinically employable.

Animals↗