Ja-Liang Lin

Environmental Exposure to Lead and Progression of Chronic Renal Diseases: A Four-Year Prospective Longitudinal Study

Previous retrospective research suggests that low-level environmental lead exposure is associated with an acceleration of age-related impairment of renal function. For elucidating the long-term relationship between low-level environmental lead exposure and progression of chronic renal diseases in patients without diabetes, 121 patients who had chronic renal insufficiency, a normal body lead burden (BLB), and no history of exposure to lead were observed prospectively for 48 mo. Associations of both BLB and blood lead level (BLL) with renal function were evaluated, with reference to other covariates. The primary end point was an increase in the serum creatinine level to double the baseline value. Sixty-three patients had BLB > or =80 microg and < 600 microg (high-normal group), and 58 patients had BLB < 80 microg (low-normal group). The primary end point occurred in 17 patients. Fifteen of them had high-normal BLB, whereas two patients had low-normal BLB (hazard ratio [95% confidence interval]: 1.01 [1.00 to 1.01] for each increment of 1 microg; P = 0.002). The BLB and BLL at baseline were the most important risk factors to predict progression of renal insufficiency. Each increase of 10 microg in the BLB or 1 microg/dl in the BLL reduced the GFR by 1.3 (P = 0.002) or 4.0 ml/min (P = 0.01) during the study period. In conclusion, low-level environmental lead exposure is associated with accelerated deterioration of renal insufficiency. Even at levels far below the normal ranges, both increased BLL and BLB predict accelerated progression of chronic renal diseases.

Acute Poisoning with the Neonicotinoid Insecticide Imidacloprid in N-Methyl Pyrrolidone

Background: Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, CAS 138261-41-3] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals because they have resistant nicotinic receptor subtypes compared to insects, as well as protection of the central nervous system by the blood brain barrier. Despite wide usage, human exposure experience resulting in toxicity is quite limited. Case Report: Here, we report a case of acute ingestion of an insecticide formulation containing 9.7% imidacloprid, <2 % surfactant, and the balance as solvent, N-methyl pyrrolidone. Clinical manifestation included drowsiness, disorientation, dizziness, oral and gastroesophageal erosions, hemorrhagic gastritis, productive cough, fever, leukocytosis, and hyperglycemia. The patient recovered without complication with supportive treatment and was discharged 4 days after ingestion. Follow-up barium upper gastrointestinal examination 1 month later was normal. Because moderate to high dose imidacloprid in animals causes central nervous system activation similar to nicotine, including tremors, impaired pupillary function, and hypothermia, it is unclear whether imidacloprid had a causal role in the patients initial drowsiness and dizziness. It is more likely that the formulation ingredients, particularly N-methyl pyrrolidone, caused most of the clinical symptoms including minor central nervous system depression, gastrointestinal irritation, and hyperglycemia.

Food safety involving ingestion of foods and beverages prepared with phthalate-plasticizer-containing clouding agents

In May 2011, the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food scandal has caused shock and panic among the majority of Taiwanese people and has attracted international attention. Phthalate exposure is assessed by ambient monitoring or human biomonitoring. Ambient monitoring relies on measuring chemicals in environmental media, foodstuff and consumer products. Human biomonitoring determines body burden by measuring the chemicals, their metabolites or specific reaction products in human specimens. In mammalian development, the fetus is set to develop into a female. Because the female phenotype is the default, impairment of testosterone production or action before the late phase may lead to feminizing characteristics. Phthalates disrupt the development of androgen-dependent structures by inhibiting fetal testicular testosterone biosynthesis. The spectrum of effects obtained following perinatal exposure of male rats to phthalates has remarkable similarities with the human testicular dysgenesis syndrome. Epidemiological studies have suggested associations between phthalate exposure and shorter gestational age, shorter anogenital distance, shorter penis, incomplete testicular descent, sex hormone alteration, precocious puberty, pubertal gynecomastia, premature thelarche, rhinitis, eczema, asthma, low birth weight, attention deficit hyperactivity disorder, low intelligence quotient, thyroid hormone alteration, and hypospadias in infants and children. Furthermore, many studies have suggested associations between phthalate exposure and increased sperm DNA damage, decreased proportion of sperm with normal morphology, decreased sperm concentration, decreased sperm morphology, sex hormone alteration, decreased pulmonary function, endometriosis, uterine leiomyomas, breast cancer, obesity, hyperprolactinemia, and thyroid hormone alteration in adults. Finally, the number of phthalate-related scientific publications from Taiwan has increased greatly over the past 5 years, which may reflect the health effects from the illegal addition of phthalate plasticizer to clouding agent in foodstuff over the past two decades.

Scrub typhus: a frequently overlooked cause of acute renal failure.

Acute renal failure associated with scrub typhus infection is not rare as previously thought. The possibility of scrub typhus should be borne in mind when patients present with fever and varying degrees of acute renal failure, particularly if an eschar exists, along with a history of environmental exposure in an area like Taiwan, where scrub typhus is endemic. Prompt diagnosis and the use of appropriate antibiotics can rapidly alter the clinical course of the disease and prevent the development of serious or fatal complications. To illustrate the above point, this study reports 3 cases of scrub typhus associated with acute renal failure. They were seen at Chang Gung Memorial Hospital in a 2-year interval. Case 1 was referred from district hospital with clinical features of multiple organ dysfunctions, including shock, fever, acute respiratory failure, acute renal failure, and acute hepatitis. Case 2 was admitted with the chief problems of shock, fever, acute renal failure, and DIC. Case 3 visited our outpatient clinic due to fever, maculopapular rash and acute renal failure. In all these patients, the diagnosis was confirmed using immunofluorescence techniques, which showed that Orientia tsutsugamushi had an IgM titer of 1:80 or greater. Notably, despite having varying degrees of acute renal deterioration, the patients responded very well to doxycycline therapy and recovered completely. Additionally, a total of 4 similar cases of scrub typhus associated with acute renal failure were reviewed from th past literature.

Environmental lead exposure and urate excretion in the general population

PURPOSE Chronic occupational exposure to lead is related to low urate excretion and a high incidence of gout in lead workers. However, whether chronic low-level environmental lead exposure influences urate excretion in the general population remains unknown. SUBJECTS AND METHODS We studied 111 healthy subjects with normal renal function (serum creatinine level < or =1.4 mg/dL) and no previous lead exposure or systemic diseases. All subjects had their blood lead levels measured, received ethylenediaminetetraacetic acid mobilization tests to assess their body lead burdens, and were investigated for renal function and urate excretion to assess the relation between lead and urate excretion. We studied urate excretion before and after lead chelation therapy in 24 subjects with high-normal body lead burden (>78 mg and <600 mg). RESULTS Healthy subjects with gout (n = 27) manifested a higher body lead burden (84 +/- 42 mg vs. 45 +/- 30 mg, P <0.0001) and lower urate clearance (3.7 +/- 1.2 mL/min/1.73 m(2) vs. 6.0 +/- 2.8 mL/min/1.73 m(2), P <0.0001) than did those without gout (n = 84). Blood lead levels and body lead burden of all subjects were within the safe range. In analyses that adjusted for age, sex, body mass index, protein intake, and creatinine clearance, blood lead level was significantly related to serum urate level (beta coefficient [+/- SE] = 0.23 +/- 0.11, P = 0.03), and body lead burdens were related to all indices of urate excretion (serum urate: beta coefficient = 0.023 +/- 0.005, P <0.0001; daily urate excretion: beta coefficient = -1.55 +/- 0.40, P = 0.0002; urate clearance: beta coefficient = -0.030 +/- 0.006, P <0.0001; fractional urate excretion: beta coefficient= -0.034 +/- 0.006, P <0.0001). Following lead chelation therapy, urate clearance increased after body lead burden was reduced (3.4 +/- 1.2 mL/min/1.73 m(2) vs. 4.9 +/- 1.4 mL/min/1.73 m(2), P <0.005). CONCLUSION Chronic low-level environmental lead exposure may inhibit urate excretion in the general population, and lead chelation therapy reduces this inhibition. These findings support efforts to reduce sources of environmental lead exposure and suggest alternative approaches to hyperuricemia and gout in the general population.

Cadmium level in seminal plasma may affect the pregnancy rate for patients undergoing infertility evaluation and treatment

This study evaluated the relationship between pregnancy rate and semen cadmium concentration. This prospective and nonrandomized clinical study analyzed 341 male partners of infertile couples undergoing infertility evaluation and management. Semen samples were collected to analyze semen quality and cadmium concentrations. The main outcome was pregnancy during 60-day infertility treatment. Simple linear regression analysis revealed an association between semen cadmium concentration NS sperm count (r=-0.150, P=0.0416) in nonsmoking subjects (n=184). In both smokers and nonsmokers, semen cadmium concentrations were significantly higher in non-pregnant patients than in pregnant patients. In nonsmokers, Cox multi-variable fertility ratio analysis demonstrated an association between semen cadmium concentration and fertility (fertility ratio of log semen cadmium=0.24; 95% confidence intervals (CI)=0.12-0.47, P<0.0001) after adjusting for related variables. Each tenfold increase in semen cadmium concentration was associated with a 4.17-fold increase in infertility ratio in nonsmoking patients. In smokers, Cox multi-variable fertility ratio analysis demonstrated that sperm count and semen cadmium concentration are associated with fertility (fertility ratio of log semen cadmium=0.17; 95% CI=0.04-0.63, P=0.0085) after adjusting for related variables. In smokers, each tenfold increase in semen cadmium concentration was associated with a 5.88-fold increase in infertility ratio. In conclusion, low levels of cadmium accumulation in semen may contribute to male infertility by reducing sperm quality.

Spectrum of toxic hepatitis following intentional paraquat ingestion: analysis of 187 cases

This retrospective observational study examined the clinical features, the degrees of toxic hepatitis, physiological markers and clinical outcomes after intentional paraquat poisoning and sought to determine what association, if any, might exist between these findings.

Effect of Long-Term Low-Dose Aluminum-Containing Agents on Hemoglobin Synthesis in Patients with Chronic Renal Insufficiency

To investigate the possible toxic effects of long-term low-dose exposure to A1-containing agents in 55 patients with chronic renal insufficiency (CRI), 37 patients received A1(OH)3 1 tablet 3 times per day (about 302 mg/day of elemental A1) for 3 months and another 18 were used as a control group. The hematological, iron status and A1 data were measured before and after the study. CRI patients who had ingested A1-containing agents for 3 months had significant decreases in hematological parameters and increases in serum A1 and daily urinary A1 excretion. Serum ferritin negatively correlated with serum A1 (r = -0.586, p < 0.0005), and hemoglobin (Hb) positively correlated with renal A1 clearance (r = 0.573, p < 0.0005) and logarithmic transformation of serum A1 (r = -0.437, p < 0.01) in these patients, despite no significant correlations between initially basal hematological and A1 parameters. But there were no significant differences between variables of A1 and hematological parameters before and after 3 months of follow-up in the control group. All factors correlating with Hb were measured with stepwise regression analysis; renal A1 clearance, creatinine clearance (Ccr) and serum iron were the most significant correlation factors with Hb. After Ccr and serum iron had been adjusted, Hb (b = 0.069 +/- 0.02; p < 0.05) still positively correlated with renal A1 clearance. Comparing patients who had reduced Hb (at least 0.5 g/dl) and those who did not, the response group had a lower basal (Ccr, a higher serum A1 and a lower renal A1 clearance after A1 loading for 3 months. In conclusion, A1 does play a role in the significant reduction of Hb and hematocrit in CRI patients after A1 loading for 3 months, and patients with a lower Ccr may easily develop A1-induced hematologically toxic effects. A1-containing agents should be used with care in long-term therapies of CRI patients.

Sequential organ failure assessment score can predict mortality in patients with paraquat intoxication.

Introduction Paraquat poisoning is characterized by multi-organ failure and pulmonary fibrosis with respiratory failure, resulting in high mortality and morbidity. The objective of this study was to identify predictors of mortality in cases of paraquat poisoning. Furthermore, we sought to determine the association between these parameters. Methods A total of 187 patients were referred for management of intentional paraquat ingestion between January 2000 and December 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and acute kidney injury network (AKIN) scores were collected, and predictors of mortality were analyzed. Results Overall hospital mortality for the entire population was 54% (101/187). Using a multivariate logistic regression model, it was found that age, time to hospitalization, blood paraquat level, estimated glomerular filtration rate at admission (eGFR first day), and the SOFA48-h score, but not the AKIN48-h score, were significant predictors of mortality. For predicting the in-hospital mortality, SOFA48-h scores displayed a good area under the receiver operating characteristic curve (AUROC) (0.795±0.033, P<0.001). The cumulative survival rate differed significantly between patients with SOFA48-h scores <3 and those ≥3 (P<0.001). A modified SOFA (mSOFA) score was further developed by using the blood paraquat level, and this new score also demonstrated a better AUROC (0.848±0.029, P<0.001) than the original SOFA score. Finally, the cumulative survival rate also differed significantly between patients with mSOFA scores <4 and ≥4 (P<0.001). Conclusion The analytical data demonstrate that SOFA and mSOFA scores, which are based on the extent of organ function or rate of organ failure, help to predict mortality after intentional paraquat poisoning.

Carbofuran-Induced Delayed Neuropathy

Background: Although carbamates have been widely used in the world for many years, carbamate-induced delayed neuropathy is rare. We report what appears to be delayed neuropathy caused by poisoning with carbofuran, a cholinesterase-inhibiting carbamate, although the certainty of diagnosis is somewhat limited by the lack of a sural nerve biopsy and spinal fluid examination. Case Report: A 23-year-old man attempted suicide by ingesting 100 mL of carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate). After recovering from acute cholinergic toxicity, he had notable paresthesia in his lower limbs and difficulty walking. Electrophysiologic findings revealed sensorimotor neuropathy. Recovery began at 1 week and continued for 4 months. A similar delayed neuropathy has been described with carbamate, 1-naphthyl N-methylcarbamate, and m-tolyl methylcarbamate, but not with carbofuran insecticides.