The effect of hypoxic ischemic encephalopathy towards multi-organ complications and its early outcome at a Malaysian district hospital.

INTRODUCTION: Hypoxic ischemic encephalopathy (HIE) is a clinically defined syndrome of disturbed neurologic function in the newborn with evidence of perinatal asphyxia. Stages of HIE are categorised into mild, moderate or severe based on the Sarnat classification. Neurological dysfunction constitutes a part of the wide spectrum of hypoxic ischemic insult as affected infants can have co-existing multi-organ dysfunction which further contributes to morbidities and mortality. This study aims to determine the relationship between the severity of HIE with multi-organ complications and early clinical outcomes. MATERIALS AND METHODS: All neonates who were admitted to the NICU at Hospital Sultan Abdul Halim between January 2018 to December 2022, who fulfilled the inclusion criteria were included. Demographic data, clinical course and investigation results were retrospectively obtained from the medical records. RESULTS: From a total of 90 infants (n = 90) who fulfilled our inclusion criteria, 31 (34%) were mild, 31 (34%) were moderate and 28 (31%) were severe HIE. The mean maternal age was 27 years. Common antenatal issues include diabetes mellitus (37.8%) and anaemia (22.2%). The Apgar scores at 1 and 5 minutes, initial resuscitation requiring intubation, chest compression and adrenaline were associated with higher severity of HIE (p < 0.05). Coagulation dysfunction was the most common complication (79.7%), followed by respiratory dysfunction (33.3%), cardiac dysfunction (28.9%), renal dysfunction (16.1%), haematological dysfunction (15.6%) and hepatic dysfunction (12%). Respiratory and haematological dysfunctions were significantly associated with higher mortality (p < 0.05). There was a significant longer hospital stay (p = 0.023), longer duration of ventilation (p < 0.001) and increase in frequency of seizures (p < 0.001) when comparing moderate and severe HIE patients to mild HIE patients. With increasing severity of HIE, there was also statistically significant higher mortality (p < 0.001). CONCLUSIONS: There is a significant relationship between multiorgan dysfunction, the severity of HIE and mortality. Early anticipation of multi-organ injury is crucial for optimal early management which would reduce the mortality and improve the neurological outcome of the patients.

A seven-year retrospective analysis of the clinicopathological and mycological manifestations of fungal rhinosinusitis in a single-centre tropical climate hospital.

OBJECTIVE: To evaluate the clinicopathological and mycological manifestations of fungal rhinosinusitis occurring in the Tengku Ampuan Rahimah Hospital, in Klang, Malaysia, which has a tropical climate. METHODS: Records of patients treated from 2009 to 2016 were analysed retrospectively. Data from the records were indexed based on age, gender, clinical presentations, symptom duration, clinical signs and mycological growth. RESULTS: Of 80 samples, 27 (33.75 per cent) had fungal growth. Sixteen patients were classified as having non-invasive fungal rhinosinusitis and 11 as having invasive fungal rhinosinusitis. The commonest clinical presentation was nasal polyposis in non-invasive fungal rhinosinusitis patients (p < 0.05) and ocular symptoms in invasive fungal rhinosinusitis patients (p < 0.05). The commonest organism was aspergillus sp. (p < 0.05) in non-invasive fungal rhinosinusitis and mucorales in invasive fungal rhinosinusitis. CONCLUSION: There is an almost equal distribution of both invasive and non-invasive fungal rhinosinusitis, as seen in some Asian countries. Invasive fungal rhinosinusitis, while slightly uncommon when compared to non-invasive fungal rhinosinusitis, is potentially life threatening, and may require early and extensive surgical debridement. The clinical presentation of nasal polyposis was often associated with non-invasive fungal rhinosinusitis, whereas ocular symptoms were more likely to be associated with invasive fungal rhinosinusitis.

Oxygen consumption is increased relative to work rate in patients with McArdle's disease.

BACKGROUND: Patients with McArdle's disease suffer exercise incapacity as a result of myophosphorylase deficiency, and for a given work rate have excessive circulatory and ventilatory responses. We hypothesized that the rate of increase of oxygen consumption with work rate (DeltaVO2-DeltaWR slope) would also be elevated in such patients as a result of these excessive responses. PATIENTS AND METHODS: Five patients with McArdle's disease and five matched controls carried out a maximal incremental cardiopulmonary exercise test. Controls then carried out a second test matched to the maximal test of a paired patient. Venous blood was sampled at rest, peak exercise and recovery. RESULTS: During the matched test, the DeltaVO2-DeltaWR slope was higher in the patients than in the controls [19.9 (15.0-24.6) vs. 11.7 (9.2-13.5) mL min(-1) W(-1); mean (range); P = 0.022], and the peak-achieved VO2 was also greater in the patient group [1201 (890-1575) vs. 918 (599-1248) mL min(-1); P = 0.003]. A similar pattern was observed for heart rate [173 (165-182) vs. 108 (105-134) b.p.m.; P = 0.001] and plasma norepinephrine levels [12.6 (9.2-19.9) vs. 2.9 (2.2-4.9) nmol l(-1); P = 0.003]. CONCLUSION: There is an increased rate of rise in VO2 relative to work rate during exercise in patients with McArdle's disease. There is also a greater rise in catecholamines, which may be the result of a physiological response to substrate starvation, and is likely to contribute to the increase in VO2.

Biological monitoring of kidney function among workers occupationally exposed to trichloroethylene.

AIMS: To investigate the nephrotoxic potential of trichloroethylene in a currently exposed population using sensitive urinary markers of kidney toxicity. METHODS: Renal dysfunction was monitored in a cross-sectional study of 70 workers currently exposed to trichloroethylene. An age and sex matched control population of 54 individuals was drawn from hospital and administrative staff. RESULTS: The mean exposure to trichloroethylene, estimated from urinary trichloroacetic acid concentrations, was 32 ppm (range 0.5-252 ppm) with an average duration of exposure of 4.1 years (range 1-20 years). Significant differences between the exposed and control populations were found for nephrotoxicity markers N-acetylglucosaminidase (NAG) and albumin, and for the mode of action marker, formic acid. However, neither NAG nor albumin showed a significant correlation with either the magnitude or duration of exposure to trichloroethylene. There was a significant correlation between urinary formic acid and trichloroacetic acid concentrations. Within the exposed population there were dose dependent increases in urinary methylmalonic acid concentrations and urinary glutathione S-transferase alpha activity. Although still within the control range, these changes were clearly dose dependent and consistent with one of the proposed mechanisms of trichloroethylene induced kidney toxicity. CONCLUSION: Although there was no evidence of kidney toxicity within the population studied, the results suggest that kidney damage could occur at exposure concentrations higher (>250 ppm) than those encountered in this study.

Can salivary lead be used for biological monitoring of lead exposed individuals?

BACKGROUND: Measurement of blood lead (BPb) is the usual method for biomonitoring of persons exposed to inorganic lead. AIM: To explore the use of salivary lead (SPb) as an alternative. METHODS: BPb and SPb levels were measured in a group of 82 lead exposed adults. RESULTS: The mean BPb of the workers was 26.6 microg/dl (SD 8.6, range 10-48) and the mean SPb level 0.77 microg/dl, or 3% of the BPb level. As the SPb distribution was skewed, logarithmic transformation was performed to normalise the distribution. A bivariate scattergram of BPb and logSPb (r = 0.41, p = 0.00) had a line of best fit expressed as BPb = 29.7 + 8.95logSPb. The relation of logSPb and BPb was stronger among non-smokers (r = 0.42) compared to smokers (r = 0.3); and among those without a medical condition (r = 0.44). Multiple linear regression analysis (fitting smoking and medical condition into the model) yielded an R of 0.54, and an adjusted R(2) of 0.26. CONCLUSION: The study findings do not support the use of SPb for biomonitoring at BPb levels ranging from 10 to 50 microg/dl.

Renal dysfunction in workers exposed to inorganic lead.

INTRODUCTION: We studied the relationship between renal dysfunction and occupational lead exposure in a local factory. MATERIALS AND METHODS: A cross-sectional study with a cohort component was conducted with 55 male workers of a factory producing PVC stabilisers as subjects. Workers from this factory have been followed up with 6-monthly blood lead measurements since 1982. Two indices of overall lead exposure, i.e. the number of times a worker's blood lead exceeded 40 micrograms/dL (PbB40) and cumulative blood lead index (PbBint), were obtained from this data. Recent blood lead concentration (PbB) was measured. 4-hour creatinine clearance and various other urinary and serum markers of renal dysfunction were used as effect indices. RESULTS: There was no relationship between PbB and any of the renal markers. However, creatinine clearance decreased significantly (P < 0.001) with increasing PbB40 and PbBint after adjustment for age and smoking habits. Urinary albumin (Ualb), urinary alpha-1 microglobulin (U alpha 1m), urinary beta-2 microglobulin (U beta 2m) and urinary retinol-binding protein (URBP) increased significantly with both increasing PbB40 and PbBint. Total urinary activity of N-acetyl-beta-D-glucosaminidase (NAG-T) and its heat-stable isoenzyme (NAG-B) increased significantly with increasing PbB40. A significant difference in renal parameters occurred when PbB40 was 1 or more. CONCLUSIONS: We have found a positive association between overall lead exposure and renal dysfunction. The renal parameters were significantly higher among those who had at least one episode of blood lead above 40 micrograms/dL. Our findings also strengthen the case for the use of Ualb, U alpha 1m, U beta 2m, URBP, NAG-T and NAG-B as early markers of lead nephropathy.

Are salivary immunoglobulin A and lysozyme biomarkers of stress among nurses?

Salivary immunoglobulin A (IgA) and lysozyme have been studied as possible biomarkers of stress. This study examined the stress levels among female nurses in various units and the relationship between these stress levels and salivary IgA and lysozyme secretion. One hundred ninety-five (43%) of 457 eligible female nurses from surgical wards/operating theaters (SURG), medical wards (MED), and outpatient clinics/day-surgery theaters (OPD) completed a self-administered questionnaire. From this group of 195 nurses, 124 provided a salivary sample accumulated over 5 minutes. Stress levels were assessed with a ten-point Stress Assessment Score (SAS) for Asians and a direct question on perceived life stress. Enzyme-linked immunosorbent assay and lyso-plate methods were used to determine salivary IgA and lysozyme levels. Forty-five percent of SURG, 35% of MED, and 17% of OPD nurses scored at least four points on the SAS. SURG nurses had the lowest IgA secretion (geometric mean; 95% confidence interval [CI]) rates (43 micrograms/min; 36 to 51 micrograms/min). The other groups had significantly higher salivary IgA secretion rates: MED (96 micrograms/min; 80 to 116 micrograms/min) and OPD (77 micrograms/min; 60 to 98 micrograms/min) Findings for salivary lysozyme (microgram/min) were similar; SURG (9 micrograms/min; 6 to 13 micrograms/min) MED (19 micrograms/min; 12 to 28 micrograms/min) and OPD (16 micrograms/min; 9 to 28 micrograms/min). The salivary IgA (Spearman's r = -0.22, P = 0.01) but not the lysozyme (Spearman's r = -0.01, P = 0.9) secretion rate correlated negatively with SAS. Nurses working in various units under different conditions experienced dissimilar levels of stress. Salivary IgA, but not lysozyme, correlated inversely with self-reported levels of stress. It may thus be a potential biomarker in future studies on stress.

High-performance liquid chromatographic determination of dehydroabietic and abietic acids in traditional Chinese medications.

In Asia, there is still a high usage of traditional Chinese medicament by the general population. Some patients with contact dermatitis to these medicaments have been found to be sensitive to colophony on patch testing. Dehydroabietic acid (DHAA) and abietic acid (AA) are the main components of colophony and believed to be the agents responsible for skin sensitization. This paper describes a reliable high-performance liquid-chromatographic method for determining these two resin acids in ointment samples. The samples were either pretreated with diethyl ether or treated with acetonitrile directly by ultrasonication for 30 min. One volume of this sample was added to an equal volume of water and purified by solid-phase extraction. The mobile phase used was methanol-water-phosphoric acid (87:13:0.02, v/v) and the flow-rate was 1 ml/min. DHAA and AA were detected at 4.3 and 6.3 men with ultraviolet detection at wavelength 200 and 239 nm, respectively. However, fluorimetric detection with an excitation wavelength of 225 nm and emission wavelength of 285 nm, provided more selective determination of DHAA. The detection limits for DHAA and AA were 1 ng. Analytical recovery generally exceeded 90%. We analyzed nine types of commonly used topical Chinese medicaments and two types of Western medical ointments in Singapore. The results showed that most of these medicaments contain colophony below 5 ppm (micrograms g-1). Only one Chinese medicament contained > 70 ppm of both allergens and one of the Western medical ointments contained 0.2% of DHAA and 2.2% of AA.

Serum DDT and DDE levels in Singapore general population.

A simple and fast method was used to determine 1,1'-(2,2,2-trichloroethylene)-bis(4-chlorobenzene) (DDT) and 1,1'-(2,2-dichloroethylidene)-bis(4-chlorobenzene) (DDE) in blood serum. Serum samples pre-treated with formic acid were extracted with n-hexane and determined by gas chromatography (GC-ECD), using PTE-5 capillary column. Detection limits for DDT and DDE were 0.5 ppb. Recovery with a fortified pooled sample at 1 ppb level was 107.0% for DDT and 106.0% for DDE. At 10 ppb level, the recoveries for DDT and DDE were 96.1% and 92.7%, respectively. Eighty-nine random blood samples collected from volunteers were analyzed. The geometric mean (GM) serum level of DDT was 1.9 ppb (0.2-8.9 ppb) and that of DDE was 10.8 ppb (1.5-88.1 ppb). There was a positive correlation between DDE and DDT level (r = 0.33, P < 0.01). The serum DDE level was positively correlated with age (r = 0.49, P < 0.01) and DDT x Age (r = 0.62, P < 0.01). No correlation was observed between DDT and age. These results suggest that DDE, a metabolite of DDT, is cumulative in the body. Therefore blood DDE could be used as a cumulative exposure marker for DDT, whereas blood DDT may be used to reflect its recent exposure.

Determination of serum and urinary aluminum by HPLC with fluorometric detection of Al-lumogallion complex.

We describe a simple and sensitive HPLC method for quantifying aluminum (Al) in biological fluids by measuring the fluorescence of the Al-lumogallion complex (excitation wavelength 500 nm, emission wavelength 575 nm). Serum samples are deproteinized with 0.83 mol/L perchloric acid and centrifuged; the supernates are mixed with lumogallion reagent. Urine samples are pretreated with sodium hydroxide (2 mol/L) and methanol, kept for 1 h at -20 degrees C, and then centrifuged; the precipitate is resuspended in perchloric acid and mixed with lumogallion reagent, as for serum. The maximal fluorescence complex is formed after 1 h at pH 5 +/- 0.5. The HPLC mobile phase consists of (per liter) 100 mL, of 0.2 mol/L potassium hydrogen phthalate, 220 mL of acetonitrile, and distilled deionized water. The flow rate is 1 mL/min, and the injection volume is 5 microliters. The major aluminum species is eluted at 3.5 min, the lowest detection limit being 0.45 pg. We validated the method with samples collected from normal subjects and from workers occupationally exposed to aluminum. Comparing the results with those by traditional atomic absorption spectrometry of urinary aluminum suggests that the proposed method is reliable.

Biomarkers of exposure to low concentrations of benzene: a field assessment.

OBJECTIVE: To carry out a comprehensive field investigation to evaluate various conventional and recently developed biomarkers for exposure to low concentrations of benzene. METHODS: Analyses were carried out on environmental air, unmetabolised benzene in blood and urine, urinary trans, transmuconic acid, and three major phenolic metabolites of benzene: phenol, catechol, and hydroquinone. Validations of these biomarkers were performed on 131 never smokers occupationally exposed to the time weighed average benzene concentration of 0.25 ppm (range, 0.01 to 3.5 ppm). RESULTS: Among the six biomarkers studied, unmetabolised benzene in urine correlated best with environmental benzene concentration (correlation coefficient, r = 0.76), followed by benzene in blood (r = 0.64). When urinary metabolites were compared with environmental benzene, trans, trans-muconic acid showed a close correlation (r = 0.53) followed by hydroquinone (r = 0.44), and to a lesser extent with urinary phenol (r = 0.38). No correlation was found between catechol and environmental benzene concentrations. Although unmetabolised benzene in urine correlates best with benzene exposure, owing to serious technical drawbacks, its use is limited. Among the metabolites, trans, trans-muconic acid seems to be more reliable than other phenolic compounds. Nevertheless, detailed analyses failed to show that it is specific for monitoring benzene exposures below 0.25 ppm. CONCLUSION: The overall results suggest that most of the currently available biomarkers are unable to provide sufficient specificity for monitoring of low concentrations of benzene exposure. If a lower occupational exposure limit for benzene is to be considered, the reliability of the biomarker and the technical limitations of measurements have to be carefully validated.

Urinary homovanillic acid and vanillylmandelic acid in workers exposed to carbon disulfide.

Homovanillic acid (HVA) and vanillylmandelic acid (VMA), two end products of dopamine metabolism, were measured in 60 workers exposed to carbon disulfide (CS(2)) in a rayon factory and in 48 unexposed workers. The airborne CS(2) concentrations in eight major exposure zones of the plant were measured monthly over a period of 4 years, from 1990 to 1994. In addition, the exposure concentrations and exposure history of each worker were integrated to estimate the overall lifetime exposure. Industrial hygiene data showed that the geometric mean concentrations of CS(2) in the plant ranged from 2.68 to 20.19 ppm, and more than 15% of the studied population had been repeatedly exposed to CS(2) at concentrations exceeding the ACGIH recommended time-weighted average of 10 ppm. The results showed that there was a significantly lower level and a higher proportion of CS(2) workers with decreased HVA and VMA excretion. However, there were no statistical correlations between the two dopaminergic metabolites and the mean CS(2) concentration, and years of employment. In contrast, significant dose-effect relationships were observed between these two metabolites and the integrated cumulative exposure (ICE) variable. The correlation coefficients for ICE and HVA, and ICE and VMA were -0.35 (p < 0.01) and -0.20 (p <0.05), respectively. These data suggest that chronic exposure to CS(2) was associated with measurable reduction in catecholamine metabolite concentrations. This finding is compatible with the earlier observations in laboratory animals that CS(2) exposures interfere with neurochemical metabolism.

Evaluation of biomarkers for occupational exposure to benzene.

OBJECTIVE: To evaluate the relations between environmental benzene concentrations and various biomarkers of exposure to benzene. METHODS: Analyses were carried out on environmental air, unmetabolised benzene in urine, trans, trans-muconic acid (ttMA), and three major phenolic metabolites of benzene; catechol, hydroquinone, and phenol, in two field studies on 64 workers exposed to benzene concentrations from 0.12 to 68 ppm, the time weighted average (TWA). Forty nonexposed subjects were also investigated. RESULTS: Among the five urinary biomarkers studied, ttMA correlated best with environmental benzene concentration (correlation coefficient, r = 0.87). When urinary phenolic metabolites were compared with environmental benzene, hydroquinone correlated best with benzene in air. No correlation was found between unmetabolised benzene in urine and environmental benzene concentrations. The correlation coefficients for environmental benzene and end of shift catechol, hydroquinone, and phenol were 0.30, 0.70, and 0.66, respectively. Detailed analysis, however, suggests that urinary phenol was not a specific biomarker for exposure below 5 ppm. In contrast, ttMA and hydroquinone seemed to be specific and sensitive even at concentrations of below 1 ppm. Although unmetabolised benzene in urine showed good correlation with atmospheric benzene (r = 0.50, P < 0.05), data were insufficient to suggest that it is a useful biomarker for exposure to low concentrations of benzene. The results from the present study also showed that both ttMA and hydroquinone were able to differentiate the background level found in subjects not occupationally exposed and those exposed to less than 1 ppm of benzene. This suggests that these two biomarkers are useful indices for monitoring low concentrations of benzene. Furthermore, these two metabolites are known to be involved in bone marrow leukaemogenesis, their applications in biological monitoring could thus be important in risk assessment. CONCLUSION: The good correlations between ttMA, hydroquinone, and atmospheric benzene, even at concentrations of less than 1 ppm, suggest that they are sensitive and specific biomarkers for benzene exposure.

Lead-induced nephropathy: relationship between various biological exposure indices and early markers of nephrotoxicity.

Lead nephropathy in adults is silent and insidious, characterized by the absence of proteinuria in its early phase. Of the early markers of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) appears to be the only one that is elevated in early lead nephropathy. However, the elevation in urinary NAG activity may be a response to a sharp increase in renal burden of lead. Its usefulness as a marker of chronic lead nephropathy is thus in doubt. There is a need, then, to identify a reliable early biological indicator of lead-induced kidney damage. Furthermore, there is also a need to identify suitable markers of chronic exposure to describe meaningful dose-response and dose-effect relationships. Traditionally, blood lead (PbB) was used, but the current blood lead level (PbBrec) is more an indicator of recent exposure. Time-integrated blood lead indices (PbBint) derived from repeated serial PbB measurements can be used as indices of chronic exposure. In 128 lead-exposed workers, the PbBint was the most important exposure variable in describing the variability in urinary alpha 1-microglobulin (U alpha 1 m), urinary beta 2-microglobulin (U beta 2m), and urinary retinol binding protein (URBP). U alpha 1m was the only marker that was significantly higher in the exposed group, with a good dose-response and dose-effect relationship with PbBint. The lack of dose-response and dose-effect relationships in other studies may be due to inappropriate exposure markers as well as less sensitive response markers. PbBint has a better correlation than PbBrec. Furthermore, U alpha 1m may be the most sensitive of the markers because of its higher molecular weight.

Glomerular function of lead-exposed workers.

Among lead-exposed workers, there is evidence of increased mortality from chronic renal diseases (nephritis and nephrosis). Epidemiological studies using early markers of nephropathy among lead-exposed workers failed to demonstrate early renal changes. This study is aimed at assessing the glomerular function of 137 lead-exposed subjects and at evaluating whether changes in markers of glomerular function are related to exposure indices derived from longitudinal blood lead data. A control group of 153 postal workers was also investigated. Several exposure indices were derived for the exposed workers, including a time-integrated index Pb in blood (PbB)int and the number of times the PbB was above critical values (PbB400, PbB500, PbB600). Through multiple linear regression analysis, PbBint was the best predictor of variation in serum beta 2-microglobulin (S beta 2m) and alpha 1-microglobulin (S alpha 1m) and urinary albumin (UA1b). A small but statistically significant difference in the mean beta 2m was found. S beta 2m was also the only marker showing a significantly higher prevalence rate ratio (PRR) of abnormalities among lead-exposed workers. Though there was no clear dose-response relationship with PbBint as the index of dose, all the 15 subjects with abnormal S beta 2m in the older age group were found in the highest PbBint group. Furthermore, of the 8 subjects with low 4-h creatinine clearance (CrCl4h), 6 had abnormal levels of beta 2m. Two subjects with CrCl4h of less than 75 ml/min/1.74 m2 had high PbBint values, thus suggesting that high blood lead levels over a prolonged time may be associated with decreased CrCl4h. Though the long-term significance of elevated S beta 2m and UA1b is unclear, their association with high PbBint and decreasing CrCl4h indicate a potentially adverse effect. Their relationship with PbB400 and PbB600 suggests that the threshold of 700 micrograms/l for PbB may not prevent the occurrence of lead nephropathy.

Determination of serum aluminium using an ion-pair reversed-phase high-performance liquid chromatographic-fluorimetric system with lumogallion.

An ion-pair reversed-phase high-performance liquid chromatographic method with fluorimetric detection, using lumogallion [4-chloro-3-(2,4-dihydroxyphenylazo)-2-hydroxybenzene-1-sulphonic acid] as a ligand, has been successfully applied to the determination of aluminium in human serum. The highly fluorescent aluminium-lumogallion complex (lambda ex 505 nm, lambda em 574 nm) was separated on a LiChrosorb RP-18 column with an eluent consisting of 30% acetonitrile, 70% 0.02 M potassium hydrogen phthalate and 10 microM lumogallion. The proposed system offers a simple, rapid, selective and sensitive method for the determination of aluminium in serum. The detection limit for aluminium was 0.05 microgram/l in aqueous solution and the limit of determination was 2.2 micrograms/l in serum. The recovery of the method is generally over 90%.