A retrospective analysis of glycol and toxic alcohol ingestion: utility of anion and osmolal gaps.

BACKGROUND: Patients ingesting ethylene glycol, isopropanol, methanol, and propylene glycol ('toxic alcohols') often present with non-specific signs and symptoms. Definitive diagnosis of toxic alcohols has traditionally been by gas chromatography (GC), a technique not commonly performed on-site in hospital clinical laboratories. The objectives of this retrospective study were: 1) to assess the diagnostic accuracy of the osmolal gap in screening for toxic alcohol ingestion and 2) to determine the common reasons other than toxic alcohol ingestion for elevated osmolal gaps. METHODS: Electronic medical records from an academic tertiary care medical center were searched to identify all patients in the time period from January 1, 1996 to September 1, 2010 who had serum/plasma ethanol, glucose, sodium, blood urea nitrogen, and osmolality measured simultaneously, and also all patients who had GC analysis for toxic alcohols. Detailed chart review was performed on all patients with osmolal gap of 9 or greater. RESULTS: In the study period, 20,669 patients had determination of serum/plasma ethanol and osmolal gap upon presentation to the hospitals. There were 341 patients with an osmolal gap greater than 14 (including correction for estimated contribution of ethanol) on initial presentation to the medical center. Seventy-seven patients tested positive by GC for one or more toxic alcohols; all had elevated anion gap or osmolal gap or both. Other than toxic alcohols, the most common causes for an elevated osmolal gap were recent heavy ethanol consumption with suspected alcoholic ketoacidosis, renal failure, shock, and recent administration of mannitol. Only 9 patients with osmolal gap greater than 50 and no patients with osmolal gap greater than 100 were found to be negative for toxic alcohols. CONCLUSIONS: Our study concurs with other investigations that show that osmolal gap can be a useful diagnostic test in conjunction with clinical history and physical examination.

Tolloid-like 1 is negatively regulated by stress and glucocorticoids.

Glucocorticoids affect a variety of tissues to enable the organism to adapt to the stress. Hippocampal neurons contain glucocorticoid receptors and respond to elevated glucocorticoid levels by down-regulating the HPA axis. Chronically, however, stress is deleterious to hippocampal neurons. Chronically elevated levels of glucocorticoids result in a decrease in the number of dendritic spines, reduced axonal growth and synaptogenesis, and decreased neurogenesis in the hippocampus. Tolloid-like 1 (Tll-1) is a metalloprotease that potentiates the activity of the bone morphogenetic proteins (BMPs). Neurogenesis in the hippocampus of both developing and adult mammals requires BMPs. In this study, we demonstrate that Tll-1 expression is increased in mice that have increased neurogenesis. The Tll-1 promoter contains glucocorticoid response elements which are capable of binding to purified glucocorticoid receptor. Glucocorticoids decrease Tll-1 expression in vitro. Finally, prenatal stress leads to a decrease in Tll-1 mRNA expression in the hippocampus of adult female mice that is not observed in adult male mice indicating that Tll-1 expression is differentially regulated in males and females. The results of this study indicate that Tll-1 is responsive to glucocorticoids and this mechanism might influence neurogenesis in the hippocampus.

Impact of the new Bethesda System 2001 on specimen adequacy of conventional cervicovaginal smears.

The Bethesda System (TBS) 2001 workshop addressed the issue of specimen adequacy by recommending the elimination of the "satisfactory but limited by" category and its replacement by a semiquantitative method for assessing squamous cellularity. The purpose of this study is to compare the rate of unsatisfactory specimens of conventional cervicovaginal smears (CVS) before and after the implementation of the TBS 2001 recommendations. TBS 2001 recommendations were implemented in our laboratory on January 1st, 2002. Data were compared from conventional CVS evaluated 6 mo prior and 6 mo after the implementation of TBS 2001. The total number of conventional CVS for the second half of 2001 was 5,808, 21 of which were considered unsatisfactory for evaluation (0.36%). Fourteen of these 21 cases had a repeat CVS, one case was diagnosed as low-grade squamous intraepithelial lesion (LSIL), and one was inadequate. In contrast, there were 288 unsatisfactory CVS out of 5,459 cases (5.3%) in the first half of 2002. Of these, 154 CVS were repeated, five cases were designated as ASCUS, and three were LSIL. Twenty-one cases had a second inadequate diagnosis, eight of these were repeated and all were negative for intraepithelial lesion or malignancy. In our laboratory, the use of the new Bethesda System guidelines yielded more than a 10-fold increase in the rate of unsatisfactory conventional CVS. This led to numerous additional office visits to obtain a repeat CVS. Only eight repeat CVS identified epithelial cell abnormalities. The implications of our findings are that TBS 2001 guidelines regarding satisfactory conventional CVS result in increased healthcare cost without identifying a significant number of new epithelial cell abnormalities.