Occupational use was associated with an increased risk of prostate cancer in a Canadian case-control study8 and in the AHS, which reported a significant trend for aggressive cancers after adjustment ...for other pesticides.9 In mice, malathion increased hepatocellular adenoma or carcinoma (combined).10 In rats, it increased thyroid carcinoma in males, hepatocellular adenoma or carcinoma (combined) in females, and mammary gland adenocarcinoma after subcutaneous injection in females.4 Malathion is rapidly absorbed and distributed. Red meat and processed meat Monograph Working Group Members A Blair (USA)--Meeting Chair; L Fritschi (Australia); J McLaughlin; C M Sergi (Canada); G M Calaf (Chile); F Le Curieux (Finland); I Baldi (France); F Forastiere (Italy); H Kromhout (Netherlands); A 't Mannetje (New Zealand); T Rodriguez unable to attend (Nicaragua); P Egeghy unable to attend, G D Jahnke; C W Jameson; M T Martin; M K Ross; I Rusyn; L Zeise (USA) Invited Specialists C Portier (Switzerland) Representatives M E Gouze, for the French Agency for Food, Environment and Occupational Health and Safety (France); J Rowland, for the US Environmental Protection Agency (USA) Observers M K Boye Jensen, for Cheminova (Denmark); B Fervers, for the Léon Bérard Centre (France); E Giroux, for University Jean-Moulin Lyon 3 (France); T Sorahan, for Monsanto Company (USA); C Strupp, for the European Crop Protection Association (Belgium); P Sutton, for the University of California, San Francisco (USA) IARC/WHO Secretariat L Benbrahim-Tallaa; R Carel; F El Ghissassi; Sonia El-Zaemey; Y Grosse; N Guha; K Z Guyton; C Le Cornet; M Leon; D Loomis; H Mattock; C Scoccianti; A Shapiro; K Straif; J Zavadil For the Preamble to the IARC Monographs see http://monographs.iarc.fr/ENG/Preamble/index.php For declarations of interests see http://monographs.iarc.fr/ENG/Meetings/vol112-participants.pdf We declare no competing interests.
It has previously been demonstrated that the risk of hypoglycemia is low among otherwise healthy elderly fasted patients with type 2 diabetes taking oral sulfonylurea medications. Nevertheless, these ...agents do cause hypoglycemia in clinical practice, suggesting that accompanying factors must typically be present for hypoglycemia to occur. Ethanol is one putative risk factor that has not been evaluated as a mechanism for low blood glucose among sulfonylurea users. We hypothesized that low concentrations of ethanol would reduce blood glucose concentrations in elderly type 2 diabetic patients receiving sulfonylureas during a short-term fast.
A total of 10 type 2 diabetic patients, aged 68 +/- 3 years and receiving 20 mg glyburide daily, participated in a prospective double-blind placebo-controlled in-patient study consisting of two 24-h fasts at least 1 week apart. During hours 14 and 15 of the fasting studies, subjects received intravenous infusions of either 4.35 mmol.kg-1.h-1 ethanol (equivalent to one or two alcoholic beverages) or saline placebo in random order. Ethanol, plasma glucose, insulin, and counterregulatory hormones were assessed very 30-60 min during the final 10 h of the fast.
Blood ethanol levels peaked at 17 +/- 2 mmol/l (the lower legal limit of intoxication in New Mexico) during the ethanol study. Plasma glucose concentrations did not differ at baseline (placebo 8.5 +/- 1.8 vs. ethanol 8.7 +/- 1.7 mmol/l; P = 0.50), but nadir plasma glucose was lower after the ethanol infusion compared with placebo (4.4 +/- 1.2 vs. 5.0 +/- 1.4 mmol/l; P = 0.01), and the absolute decline in plasma glucose was also greater during the ethanol study than the placebo study (4.7 +/- 0.9 vs. 3.6 +/- 1.2 mmol/l; P = 0.01). Counterregulatory hormone levels were increased during the ethanol study and nonesterified fatty acid concentrations were suppressed compared with the placebo study.
Low doses of ethanol predispose fasted elderly type 2 diabetic patients to low blood glucose during a short-term fast. This may be one of several mechanisms by which sulfonylurea-induced hypoglycemia occurs in elderly patients.
Lispro is a new rapidly absorbed insulin analog. At present, there are no recommendations for the optimal injection time of lispro insulin in hyperglycemic patients. In contrast to normoglycemic ...patients with diabetes, we hypothesized that injection of lispro insulin 15-30 min before meal ingestion would improve postprandial glucose excursion in hyperglycemic diabetic subjects.
In 48 randomized overnight studies, 12 healthy adult type 1 diabetic patients received lispro insulin 0.15 U/kg admixed with human ultralente 0.2 U/kg (as background insulin) subcutaneously at minutes (-30, -15, 0, and +15) relative to the ingestion of an American Diabetes Association breakfast of 8.6 kcal/kg. Pre-breakfast hyperglycemia of 10.2 +/- 0.2 mmol/l was established before the study by continuous overnight infusion of intravenous insulin, which was stopped 30 min before lispro insulin injection. Glucose and insulin levels were measured every 30 min for 5 h after breakfast.
Results demonstrated that postprandial glucose excursion was reduced when lispro insulin was administered 15 or 30 min before the meal compared with lispro insulin injected at the meal (P < 0.002). The postprandial glucose excursion (millimoles per liter per hour) was -6.4 +/- 3 for the -30-min group, -5.1 +/- 2.9 for the -15-min group, 3.4 +/- 4.1 for the 0-min group, and 5.7 +/- 4.4 for the +15-min group. Although injecting lispro insulin at 30 min before the meal resulted in a significant reduction in postprandial glycemia, it was accompanied by loss of glucose control at 4 h postmeal in two subjects.
Optimization of lispro insulin in hyperglycemic patients requires timing of the insulin injection at least 15 min before the meal.
Risks of Complication Following Thyroidectomy Burge, Mark R.; Zeise, Tanja‐Maria; Johnsen, Michael W. ...
Journal of general internal medicine,
January 1998, 1998, 1998-Jan, 1998-1-00, 19980101, Letnik:
13, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
OBJECTIVE:
Because hypoparathyroidism is a serious complication of thyroidectomy, we attempted to elucidate factors determining the risk of this postoperative outcome.
SETTING:
Four tertiary care ...hospitals in Albuquerque, New Mexico.
PATIENTS:
A retrospective study of 142 patients who underwent total or subtotal thyroidectomy between 1988 and 1995.
MEASUREMENTS AND MAIN RESULTS:
Permanent hypoparathyroidism was defined as hypocalcemic symptoms plus a requirement for oral vitamin D or calcium 6 months after thyroidectomy. Factors analyzed to determine their contribution to the risk of persistent postoperative hypoparathyroidism were the indication for thyroidectomy, performance of a preoperative thyroid needle biopsy, type of surgery, postoperative pathology, presence and stage of thyroid carcinoma, resident surgeon involvement, and specialty of the surgeon performing the procedure. Surgical specialty and stage of thyroid carcinoma were independent risk factors for persistent postoperative hypoparathyroidism by multivariate analysis. Nine (29%) of 31 patients who had thyroidectomy by otolaryngologists met criteria for permanent hypoparathyroidism, and 6 (5%) of 111 patients who had thyroidectomy by general surgeons met the same criteria ( p < .001). Adjustment for the effect of stage did not eliminate the effect of specialty ( p= .006), and adjustment for the effect of specialty did not eliminate the effect of stage ( p= .02), on the occurrence of postoperative hypoparathyroidism.
CONCLUSIONS:
We conclude from our data that patients undergoing thyroidectomy by an otolaryngologist may be at a higher risk of permanent postoperative hypoparathyroidism than patients who undergo thyroidectomy by a general surgeon. This may reflect differences in case selection or surgical approach or both.
KEY WORDS:
thyroidectomy; surgical complications; hypoparathyroidism; hypocalcemia; thyroid carcinoma.
Migrainous vertigo (MV) is an increasingly recognized cause of episodic vertigo. However, the pathophysiology of MV is still a matter of speculation and it is not known to what extent the dysfunction ...is located in the central or peripheral vestibular system. The aim of this prospective study was to describe the clinical spectrum of acute MV and to clarify which structures of the vestibular system are involved. Testing of 20 patients with acute MV included neuro-otological examination, recording of spontaneous and positional nystagmus with 3D video-oculography, and audiometry. Pathological nystagmus was observed in 70% of patients during acute MV: six had isolated spontaneous nystagmus, five had isolated positional nystagmus and three had a combination of the two. Only a few patients showed additional ocular motor deficits. Imbalance was observed in all patients except one. Hearing was not affected in any patient during the attack. The findings during acute MV point to central–vestibular dysfunction in 10 patients (50%) and to peripheral vestibular dysfunction in three patients (15%). In the remaining seven patients (35%) the site of involvement could not be determined with certainty. MV should be considered in the differential diagnosis of vertigo with spontaneous and positional nystagmus and can present both as a central and a peripheral vestibular disorder.
There are reports of developmental and reproductive health effects associated with the widely used biocide triclosan.
Apply the Navigation Guide systematic review methodology to answer the question: ...Does exposure to triclosan have adverse effects on human development or reproduction?
We applied the first 3 steps of the Navigation Guide methodology: 1) Specify a study question, 2) Select the evidence, and 3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the number and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-analysis on a subset of suitable data.
We found 4282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concentration outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-analysis. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-analysis of the human data. Through meta-analysis of the data for rats, we estimated for prenatal exposure a 0.09% (95% CI: −0.20, 0.02) reduction in thyroxine concentration per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estimated a 0.31% (95% CI: −0.38, −0.23) reduction in thyroxine per mg triclosan/kg-bw, also compared to control. Overall, we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a “moderate/low” quality rating to the body of evidence for human thyroid hormone alterations and a “moderate” quality rating to the body of evidence for non-human thyroid hormone alterations.
Based on this application of the Navigation Guide systematic review methodology, we concluded that there was “sufficient” non-human evidence and “inadequate” human evidence of an association between triclosan exposure and thyroxine concentrations, and consequently, triclosan is “possibly toxic” to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Additional endpoints may be identified as being of equal or greater concern as other data are developed or evaluated.
•The Navigation Guide was applied to evaluate adverse effects of triclosan.•There was inadequate human evidence of an association between triclosan and T4.•Meta-analysis indicated a triclosan-induced dose-dependent decrease in T4 in rats.•Triclosan was rated “possibly toxic” to reproductive and developmental health.
Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear.
To conduct a systematic review on the combined ...impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes.
We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES).
We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification.
We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.
Chloral hydrate is commonly used to sedate children for diagnostic or therapeutic procedures. The drug has been extensively used for many years, but there are remarkably few data on its long-term ...health effects. Concern in this regard is raised by recent studies showing chloral hydrate to be genotoxic, causing chromosome changes and other effects in vivo and in vitro. In addition, chloral hydrate is a reactive metabolite of trichloroethylene, a known carcinogen, and is structurally similar to other carcinogenic intermediates. Two carcinogenicity studies performed using the oral route of administration in mice indicate that the drug is potentially carcinogenic--in one case after a single dose lower than the typical dose used for sedation. Practitioners should be aware of chloral hydrate's genotoxicity and potential carcinogenicity. Discretion in its use seems appropriate until further studies clarify its long term health consequences.
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