Peak insulin drip rate associated with decreased infections post-solid organ transplant.

Infection and rejection outcomes were retrospectively analyzed in patients following liver transplant and separately following heart transplant with patients being stratified by their severity of immediate postoperative insulin resistance as measured by the peak insulin drip rate that was required to reduce glucose levels. For each group, these peak insulin drip rates were divided into quartiles (Q). In liver transplant patients (n = 207), those in Q4 (highest infusion rate) had significantly fewer infections up to 6 months post-transplant (42.3% vs. 60.0%, p = .036) and borderline fewer rejection episodes (25.0% vs. 40.0%, p = .066) compared to Q1-Q3 patients. To confirm these unexpected results, a subsequent similar analysis in heart transplant (n = 188) patients again showed that Q4 patients had significantly fewer infections up to 6 months (19.1% vs. 53.9%, p < .0001) compared to Q1-Q3 patients. Logistic regression in a subset of 103 cardiac transplant patients showed that the maximum glucose during surgery, prior MI, and hypertension were associated with severe insulin resistance (SIR) status, while the presence of pre-existing diabetes and BMI were not. We hypothesize that patients are who are able to mount a more robust counter-regulatory response that causes the insulin resistance may be healthier and thus able to mount a better response to infections.

Can drawing instruction help students with low visuospatial ability in learning anatomy?

Visuospatial skills are considered important attributes when learning anatomy and there is evidence suggesting that this ability can be improved with training techniques including drawing. The Mental Rotations Test (MRT) has been routinely used to assess visuospatial ability. This study aimed to introduce students to drawing as a learning strategy for anatomy. Undergraduate speech science anatomy students took part in a drawing tutorial (n = 92), completed an MRT test, pre- and post-tutorial tests, and surveys regarding their use and attitudes toward drawing as a study tool. The impact on their examination performance was then assessed. Regardless of MRT score or attitude to drawing, students who participated in the drawing tutorial demonstrated immediate improvement in post-tutorial test scores. Students in the drawing group performed better in most anatomy components of the examination, but the result did not reach statistical significance. There was only a positive correlation between MRT score and one type of anatomy question (non-image-based) and speech physics questions (r = 0.315, p = 0.002). The unexpected finding may relate to the MRT which assesses spatial rather than object visualization skills. Students who liked drawing also performed significantly better in word-based and speech physics questions. It is likely that the style of identification question did not require the mental manipulation ability assessed in the MRT. This study demonstrated that students with lower MRT scores are not outperformed in all aspects of anatomy assessment. The study highlights the importance of a more nuanced understanding of visuospatial skills required in anatomy.

Fetal hypoxia and hyperglycemia in the formation of phenytoin-induced cleft lip and maxillary hypoplasia.

OBJECTIVE: Phenytoin exposure during the first trimester of pregnancy increases the risk of maxillary hypoplasia and cleft lip. The etiology of phenytoin embryopathy is unknown. Interestingly, phenytoin is also known to induce hyperglycemia in humans as well as rats. This study uses a rat model of fetal phenytoin syndrome to examine the role of hyperoxia, hyperglycemia, and arachidonic acid deficiency in the development of cleft lip and maxillary hypoplasia. METHODS: Pregnant rats were dosed with phenytoin during the critical period of lip development (day 11 of pregnancy) with or without supplemental oxygen, insulin, or arachidonic acid. The fetuses from all studies were examined at term. RESULTS: The frequency of cleft lip and maxillary hypoplasia was reduced by treating dams at the time of phenytoin exposure with either increased oxygen or insulin. However, in fetuses from phenytoin-treated dams dosed with arachidonic acid, the incidence of severe lip deformities remained the same although there was an increase in normal and mildly affected fetuses. Interestingly, this occurred in embryos from hyperglycemic dams. SIGNIFICANCE: Together, the results from these experiments suggest phenytoin-induced malformations may be a multifactorial process as malformations were not solely linked to a hyperglycemic state of the dam.

Calls to a Major Teratogen Information Service Regarding Exposures During Breastfeeding.

Background: MotherSafe is a free telephone-based counseling service for Australian consumers and health care providers concerned about drug exposures during pregnancy and breastfeeding. Calls relating to breastfeeding are relatively common and a source of significant distress to the breastfeeding mother, particularly if there is a lack of clarity regarding possible adverse effects of drug exposure on the infant. This study seeks to identify the medication exposures of concern for breastfeeding mothers and the information available to address these concerns. Aims: To review calls to MotherSafe about breastfeeding drug exposures during the 19-year period from 2000 to 2018 and to highlight drugs of concern and counseling issues. Materials and Methods: A retrospective descriptive assessment of a prospectively collected Access database was undertaken. Phone counseling records identified the medication (and other) exposures of concern regarding breastfeeding. The information about medication exposures via breastfeeding provided in consumer and product information (PI) was also reviewed. Results: Of a total of 315,158 calls received at MotherSafe between 2000 and 2018, 116,876 (37.1%) were regarding drug exposure via breastfeeding; 30% of these calls related to nonsteroidal anti-inflammatory drugs, antihistamines, antidepressants, simple analgesics, and antibiotics, and 5% were regarding an exposure specifically contraindicated when breastfeeding. Conclusions: Queries about medication exposures via breastfeeding represent a significant proportion of all the counseling calls to MotherSafe. This study demonstrates the inconsistent and often misleading information about breastfeeding exposures found in consumer and PI sheets and online and highlights the important role of Teratogen Information Services like MotherSafe in providing evidence-based information to both consumers and health care providers.

Using the Jigsaw Method to Teach Abdominal Anatomy.

This study evaluates a cooperative learning approach for teaching anatomy to health science students incorporating small group and peer instruction based on the jigsaw method first described in the 1970's. Fifty-three volunteers participated in abdominal anatomy workshops. Students were given time to become an "expert" in one of four segments of the topic (sub-topics) by allocating groups to work-stations with learning resources: axial computerized tomography (CT) of abdominal structures, axial CT of abdominal blood vessels, angiograms and venograms of abdominal blood vessels and structures located within abdominal quadrants. In the second part of workshop, students were redistributed into "jigsaw" learning groups with at least one "expert" at each workstation. The "jigsaw" learning groups then circulated between workstations learning all sub-topics with the "expert" teaching others in their group. To assess abdominal anatomy knowledge, students completed a quiz pre- and post- workshop. Students increased their knowledge with significant improvements in quiz scores irrespective of prior exposure to lectures or practical classes related to the workshop topic. The evidence for long-term retention of knowledge, assessed by comparing end-semester examination performance of workshop participants with workshop nonparticipants, was less convincing. Workshop participants rated the jigsaw workshop highly for both educational value and enjoyment and felt the teaching approach would improve their course performance. The jigsaw method improved anatomy knowledge in the short-term by engaging students in group work and peer-led learning, with minimal supervision required. Reported outcomes suggest that cooperative learning approaches can lead to gains in student performance and motivation to learn. Anat Sci Educ 00: 000-000. © 2018 American Association of Anatomists.

Hyperglycemia in the Posttransplant Period: NODAT vs Posttransplant Diabetes Mellitus.

OBJECTIVE: To characterize the types of hyperglycemia that occur up to 1 year following liver transplant and to clarify the nomenclature for posttransplant hyperglycemia. DESIGN: We analyzed 1-year glycemic follow-up data in 164 patients who underwent liver transplant and who had been enrolled in a randomized controlled trial comparing moderate to intensive insulin therapy to determine if patients had preexisting known diabetes, transient hyperglycemia, persistent hyperglycemia, or new-onset diabetes after transplantation (NODAT). RESULTS: Of 119 patients with posttransplant hyperglycemia following hospital discharge, 49 had preexisting diabetes, 5 had insufficient data for analysis, 48 had transient hyperglycemia (16 resolved within 30 days and 32 resolved between 30 days and 1 year), 13 remained persistently hyperglycemic out to 1 year and most likely had preexisting diabetes that had not been diagnosed or insulin resistance/insulinopenia prior to transplant, and 4 had NODAT (i.e., patients with transient hyperglycemia after transplant that resolved but then later truly developed sustained hyperglycemia, meeting criteria for diabetes). CONCLUSIONS: Distinct categories of patients with hyperglycemia following organ transplant include known preexisting diabetes, persistent hyperglycemia (most likely unknown preexisting diabetes or insulin resistance/insulinopenia), transient hyperglycemia, and NODAT. Those with preexisting diabetes for many years prior to transplant may well have very different long-term outcomes compared with those with true NODAT. Therefore, it would be prudent to classify patients more carefully. Long-term outcome studies are needed to determine if patients with true NODAT have the same poor prognosis as patients with preexisting diabetes (diagnosed and undiagnosed) undergoing transplant.

Validation of data from electronic data warehouse in diabetic ketoacidosis: Caution is needed.

AIMS: This study validated enterprise data warehouse (EDW) data for a cohort of hospitalized patients with a primary diagnosis of diabetic ketoacidosis (DKA). METHODS: 247 patients with 319 admissions for DKA (ICD-9 code 250.12, 250.13, or 250.xx with biochemical criteria for DKA) were admitted to Northwestern Memorial Hospital from 1/1/2010 to 9/1/2013. Validation was performed by electronic medical record (EMR) review of 10% of admissions (N = 32). Classification of diabetes type (Type 1 vs. Type 2) and DKA clinical status were compared between the EMR review and EDW data. RESULTS: Key findings included incorrect classification of diabetes type in 5 of 32 (16%) admissions and indeterminable classification in 5 admissions. DKA was not present, based on the review, in 11 of 32 (34%) admissions. DKA was not present, based on biochemical criteria, in 15 of 32 (47%) admissions. CONCLUSIONS: This study found that EDW data have substantial errors. Some discrepancies can be addressed by refining the EDW query code, while others, related to diabetes classification and DKA diagnosis, cannot be corrected without improving clinical coding accuracy, consistency of medical record documentation, or EMR design. These results support the need for comprehensive validation of data for complex clinical populations obtained through data repositories such as the EDW.

Risk assessment of the hospital discharge process of high-risk patients with diabetes.

OBJECTIVES: Describe the application of a risk assessment to identify failures in the hospital discharge process of a high-risk patient group, liver transplant (LT) recipients with diabetes mellitus (DM) and/or hyperglycaemia who require high-risk medications. DESIGN: A Failure Modes, Effects and Criticality Analysis (FMECA) of the hospital discharge process of LT recipients with DM and/or hyperglycaemia who required DM education and training before discharge was conducted using information from clinicians, patients and data extraction from the electronic health records (EHR). Failures and their causes were identified and the frequency and characteristics (harm, detectability) of each failure were assigned using a score of low/best (1) to high/worst (10); a Criticality Index (CI=Harm×Frequency) and a Risk Priority Number (RPN=Harm×Frequency×Detection) were also calculated. SETTING: An academic, tertiary care centre in Chicago, Illinois. PARTICIPANTS: Healthcare providers (N=31) including physicians (n= 6), advanced practice providers (n=12), nurses (n=6), pharmacists (n= 4), staff (n=3) and patients (n=6) and caregivers (n=3) participated in the FMECA; EHR data for LT recipients with DM or hyperglycaemia (N=100) were collected. RESULTS: Of 78 identified failures, the most critical failures (n=15; RPNs=700, 630, 560; CI=70) were related to variability in delivery of diabetes education and training, care coordination and medication prescribing patterns of providers. Underlying causes included timing of patient education, lack of assessment of patients' knowledge and industry-level design failures of healthcare products (eg, EHR, insulin pen). CONCLUSION: Most identified critical failures are preventable and suggest the need for the design of interventions, informed by the failures identified by this FMECA, to mitigate safety risks and improve outcomes of high-risk patient populations.

Early Gestational Hypoxia and Adverse Developmental Outcomes.

Hypoxia is a normal and essential part of embryonic development. However, this state may leave the embryo vulnerable to damage when oxygen supply is disturbed. Embryofetal response to hypoxia is dependent on duration and depth of hypoxia, as well as developmental stage. Early postimplantation rat embryos were resilient to hypoxia, with many surviving up to 1.5 hr of uterine clamping, while most mid-gestation embryos were dead after 1 hour of clamping. Survivors were small and many had a range of defects, principally terminal transverse limb reduction defects. Similar patterns of malformations occurred when embryonic hypoxia was induced by maternal hypoxia, interruption of uteroplacental flow, or perfusion and embryonic bradycardia. There is good evidence that high altitude pregnancies are associated with smaller babies and increased risk of some malformations, but these results are complicated by increased risk of pre-eclampsia. Early onset pre-eclampsia itself is associated with small for dates and increased risk of atrio-ventricular septal defects. Limb defects have clearly been associated with chorionic villus sampling, cocaine, and misoprostol use. Similar defects are also observed with increased frequency among fetuses who are homozygous for thalassemia. Drugs that block the potassium current, whether as the prime site of action or as a side effect, are highly teratogenic in experimental animals. They induce embryonic bradycardia, hypoxia, hemorrhage, and blisters, leading to transverse limb defects as well as craniofacial and cardiovascular defects. While evidence linking these drugs to birth defects in humans is not compelling, the reason may methodological rather than biological. Birth Defects Research 109:1358-1376, 2017.© 2017 Wiley Periodicals, Inc.

Counselling regarding paternal exposures: Can we do better?

BACKGROUND: MotherSafe is a free telephone-based counselling service for the general public and healthcare providers concerned about exposures during pregnancy and breastfeeding. Calls relating to paternal exposures are less common, but can cause distress to the person concerned. This review seeks to identify the key concerns and what information is available to address these concerns. AIMS: To review calls made to MotherSafe about paternal exposures to teratogens during the 16 year period, 2000-2015, and to document any patterns or changes in calls over the period. MATERIALS AND METHODS: A retrospective descriptive assessment of a prospectively collected database (2000-2015) was undertaken. Telephone counselling records identified the drugs of concern regarding paternal exposures. The information about paternal exposures provided in consumer and production information was also reviewed. RESULTS: Of a total of 253 103 calls received at MotherSafe between 2000 and 2015, 1072 calls (0.4%) were regarding paternal exposures. The majority of these calls related to immunomodifiers (19%), hair loss products (11%) and antidepressant medications. CONCLUSIONS: Paternal exposures represent a small proportion of all the counselling calls made to MotherSafe. The study highlighted the deficient and often misleading information about paternal exposures found in most consumer and product information sheets or via the internet. The study indicates the important role of Teratogen Information Services like Mothersafe in providing evidence-based information to both consumers and healthcare providers.

Glycemic Control Reduces Infections in Post-Liver Transplant Patients: Results of a Prospective, Randomized Study.

Context: Previous studies have shown a relationship between glycemic control and posttransplant morbidity. Objective: We conducted a prospective randomized controlled trial in postliver transplant patients to evaluate intensive inpatient glycemic control and effects on outcomes to 1 year. Research Design and Intervention: A total of 164 patients [blood glucose (BG) >180 mg/dL] were randomized into 2 target groups: 82 with a BG of 140 mg/dL and 82 with a BG of 180 mg/dL. Continuous insulin infusions were initiated and then converted to subcutaneous basal bolus insulin therapy by our glucose management service. Results: The inpatient mean BG level was significantly different (140 group, 151.4 ± 19.5 mg/dL vs 180 group, 172.6 ± 27.9 mg/dL; P < 0.001). Any infection within 1 year occurred in 35 of the 82 patients (42.7%) in the 140 group and 54 of 82 (65.9%) in the 180 group (P = 0.0046). In a time-to-first infection analysis, being in the 140 group resulted in a hazard ratio of 0.54 (95% confidence interval, 0.35 to 0.83; P = 0.004); the difference between the 2 groups was statistically significant at 1 month (P = 0.008). The number with adjudicated transplant rejection was similar between the 2 groups [17 of 82 (20.7%) and 20 of 82 (24.3%) in the 140 and 180 groups, respectively; P = not significant]. Severe hypoglycemia (BG ≤40 mg/dL) occurred in 3 patients (2 in the 140 group and 1 in the 180 group). However, more patients had moderate hypoglycemia (BG, 41 to 70 mg/dL) in the 140 group [27 of 82 (32.9%) vs 10 of 82 (12.2%) in the 180 group; P = 0.003]. Insulin-related hypoglycemia was not associated with the incidence of severe adverse outcomes. Conclusions: Glycemic control of 140 mg/dL safely resulted in a reduced incidence of infection after transplantation compared with 180 mg/dL, but with an increase in moderate hypoglycemia.

EVALUATION OF OUTCOMES AND COMPLICATIONS IN PATIENTS WHO EXPERIENCE HYPOGLYCEMIA AFTER CARDIAC SURGERY.

OBJECTIVE: The objective of the study was to elucidate 30-day and long-term outcomes in patients experiencing postoperative hypoglycemia. METHODS: We conducted a retrospective review of patients who underwent cardiac surgery between September 4, 2007, and April 30, 2011, at Northwestern Memorial Hospital who had intensive treatment of hyperglycemia postoperatively. Of 1,325 patients, 215 experienced a hypoglycemic episode (blood glucose <70 mg/dL) within the first 3 postoperative days. A total of 198 were propensity-score (PS) matched to 363 patients without hypoglycemia. The analysis consisted of a comparison of 30-day cardiac outcomes and long-term mortality between those who experienced a hypoglycemic event and those who did not. RESULTS: Between patients who experienced hypoglycemia compared to those that did not, there were no significant differences in mean glucose values while on insulin drips (119.8 ± 33.5 mg/dL vs. 120.9 ± 30.5 mg/dL; P = .69) or subcutaneous insulin (122.0 ± 38.0 mg/dL vs. 127.2 ± 35.5 mg/dL; P = .11) or postoperative surgical complication rates (30-day mortality: 3.5% vs. 1.7%; complications (any): 40% vs. 42%; 30-day re-admissions: 13% vs. 13%; all cardiac complications: 35% vs. 31%; and all infections: 8% vs. 5%). Over an average of 5.1 ± 2.2 years following index surgery, there was higher all-cause mortality among those PS-matched who had experienced hypoglycemia compared to those who had not (log-rank P = .031), primarily due to those (n = 32) experiencing more than one episode of hypoglycemia. CONCLUSION: Postoperative hypoglycemia did not negatively impact immediate surgical complication rates but was associated with a significant risk of increased postoperative morbidity and long-term all-cause mortality in patients experiencing multiple episodes of hypoglycemia. ABBREVIATIONS: BG = blood glucose BMI = body mass index CARD = Cardiovascular Research Database HR = hazard rate PS = propensity score.

INPATIENT HYPOGLYCEMIC EVENTS IN A COMPARATIVE EFFECTIVENESS TRIAL FOR GLYCEMIC CONTROL IN A HIGH-RISK POPULATION.

OBJECTIVE: Inpatient hypoglycemia (glucose ≤70 mg/dL) is a limitation of intensive control with insulin. Causes of hypoglycemia were evaluated in a randomized controlled trial examining intensive glycemic control (IG, target 140 mg/dL) versus moderate glycemic control (MG, target 180 mg/dL) on post-liver transplant outcomes. METHODS: Hypoglycemic episodes were reviewed by a multidisciplinary team to calculate and identify contributing pathophysiologic and operational factors. A subsequent subgroup case control (1:1) analysis (with/without) hypoglycemia was completed to further delineate factors. A total of 164 participants were enrolled, and 155 patients were examined in depth. RESULTS: Overall, insulin-related hypoglycemia was experienced in 24 of 82 patients in IG (episodes: 20 drip, 36 subcutaneous [SQ]) and 4 of 82 in MG (episodes: 2 drip, 2 SQ). Most episodes occurred at night (41 of 60), with high insulin amounts (44 of 60), and during a protocol deviation (51 of 60). Compared to those without hypoglycemia (n = 127 vs. n = 28), hypoglycemic patients had significantly longer hospital stays (13.6 ± 12.6 days vs. 7.4 ± 6.1 days; P = .002), higher peak insulin drip rates (17.4 ± 10.3 U/h vs. 13.1 ± 9.9 U/h; P = .044), and higher peak insulin glargine doses (36.8 ± 21.4 U vs. 26.2 ± 24.3 U; P = .035). In the case-matched analysis (24 cases, 24 controls), those with insulin-related hypoglycemia had higher median peak insulin drip rates (17 U/h vs. 11 U/h; P = .04) and protocol deviations (92% vs. 50%; P = .004). CONCLUSION: Peak insulin requirements and protocol deviations were correlated with hypoglycemia. ABBREVIATIONS: DM = diabetes mellitus ICU = intensive care unit IG = intensive glycemic control MELD = Model for End-stage Liver Disease MG = moderate glycemic control SQ = subcutaneous.

The Effect of Dofetilide on the Heart Rate of GD11 and GD13 Rat Embryos, in vivo, Using Ultrasound.

BACKGROUND: There are a wide range of drugs including antidepressants, anticonvulsants and antipsychotics that cause embryonic bradycardia in vitro but it is unknown if they have a similar effect in vivo. One way to verify whether these in vitro findings are replicated in vivo is by the use of ultrasound examination of dosed pregnant rats. We tested this by examining the effect of dofetilide on embryonic heart rate (HR) in vivo using ultrasound. METHODS: Rats were dosed with dofetilide (4 or 2.5 mg/kg) on GD11 or (5 or 2.5 mg/kg) on GD13 and embryonic HR assessed by ultrasound, 2 and 24 hr later. Fetuses were examined for malformations on GD20. RESULTS: HR of control rat embryos showed a wide range at each gestational day. Dosing with dofetilide on GD11 caused severe bradycardia (∼ 60% reduction) 2 hours after dosing with recovery after 24 h of >60% of LD but death and slow HR among the HD embryos. At term, 32% of the LD surviving fetuses had hypoplastic upper lip while >90% of HD embryos had died. On GD13, embryonic HR was reduced in a dose-dependent manner with >85% of LD and HD recovered by 24 hr. At term, all LD fetuses were normal while 29% of HD fetuses had limb defects. CONCLUSIONS: Ultrasound is a useful technique to investigate the effect of maternally administered drugs on the embryonic HR in the rat. The results may provide more information about the safety of these drugs in pregnancy leading to better risk assessment for the human.

Comparison of glycemic and surgical outcomes after change in glycemic targets in cardiac surgery patients.

OBJECTIVE: To compare perioperative glycemic and long-term surgical outcomes in patients undergoing cardiac surgery before and after the recommended 2009 changes in inpatient glycemic targets. RESEARCH DESIGN AND METHODS: We performed a retrospective review of patients who underwent cardiac surgery between 4 September 2007 and 30 April 2011. Comparison was made of blood glucose (BG) outcomes 3 days after surgery, and 30-day cardiac outcomes before and after a change in insulin protocol that took place on 1 September 2009, which consisted of raising the glycemic targets during intravenous insulin infusions from 80-110 mg/dL (80-110 group) to 110-140 mg/dL (110-140 group). RESULTS: When compared with the 80-110 group (n = 667), the 110-140 group (n = 658) had higher mean postoperative BG levels during the intravenous insulin infusion (141 ± 15 vs. 121 ± 15 mg/dL, P < 0.001) and the subcutaneous insulin period (134 ± 24 vs. 130 ± 23 mg/dL, P < 0.001), and for 3 days postoperatively (141 ± 17 vs. 127 ± 15 mg/dL, P < 0.001). Fewer patients in the 110-140 mg/dL group experienced moderate hypoglycemia (BG <70 mg/dL) (177 vs. 73, P = 0.04). Severe hypoglycemia (BG <40 mg/dL) occurred in only one patient in the 80-110 group and three patients in the 110-140 group. There were no significant differences in mortality or surgical complication rates (with the exception of reintubation) between the groups. CONCLUSIONS: The higher glycemic target of 110-140 mg/dL resulted in similar mean glucose values, with significantly less hypoglycemia and no significant differences in mortality/morbidity compared with the more strict target of 80-110 mg/dL.

Examination of implementation of intravenous and subcutaneous insulin protocols and glycemic control in heart transplant patients.

OBJECTIVE: Perioperative glycemic management is particularly challenging in heart transplant (HT) patients who are on high-dose steroids and subject to surgical stress. The objective of the study was to examine the efficacy and safety of perioperative insulin administration in HT patients with and without diabetes. METHODS: Medical records of 71 HT patients from June 1, 2005 to July 31, 2009 whose hyperglycemia was managed by our Glucose Management Service (GMS) were analyzed for up to 1 year after HT. Their daily blood glucose (BG) averages on intravenous (i.v.) insulin drips and subcutaneous (s.q.) insulin, hypoglycemia rates, reasons for hypoglycemia, and deviations from insulin protocols were analyzed. RESULTS: Daily BG averages between diabetic (DM) and nondiabetic (nonDM) patients were not significantly different while on the drip but were significantly different for first 5 days on s.q. (P<.05). The daily insulin glargine doses were similar. No patients developed severe hypoglycemia (BG ≤40 mg/dL) while on drip, and only 2.8% experienced hypoglycemia on s.q. Among 40 episodes of moderate hypoglycemia while on drip, 15 had nurse deviations from protocol prior to the episode. Posttransition day fasting glucose was at goal (mean 124.7 ± 35.4 mg/dL); however 39.4% (28/71) of patients received a transition insulin glargine dose that was different from the amount indicated by protocol. The likelihood of developing moderate hypoglycemia on s.q. was associated with the glargine dose used at the time of transition (odds ratio [OR] 1.03, P = .034). CONCLUSION: Inpatient insulin protocols implemented by a GMS are successful in obtaining glycemic control with minimal side effects in patients with and without diabetes, even when they are on a high-dose steroid regimen.

Intensive glycemic control after heart transplantation is safe and effective for diabetic and non-diabetic patients.

Some studies have shown increased mortality, infection, and rejection rates among diabetic (DM) compared to non-diabetic (non-DM) patients undergoing heart transplant (HT). This is a retrospective chart review of adult patients (DM, n = 26; non-DM, n = 66) undergoing HT between June 1, 2005, and July 31, 2009. Glycemic control used intravenous (IV) and subcutaneous (SQ) insulin protocols with a glucose target of 80-110 mg/dL. There were no significant differences between DM and non-DM patients in mean glucose levels on the IV and SQ insulin protocols. Severe hypoglycemia (glucose <40 mg/dL) did not occur on the IV protocol and was experienced by only 3 non-DM patients on the SQ protocol. Moderate hypoglycemia (glucose >40 and <60 mg/dL) occurred in 17 (19%) patients on the IV protocol and 24 (27%) on the SQ protocol. There were no significant differences between DM and non-DM patients within 30 d of surgery in all-cause mortality, treated HT rejection episodes, reoperation, prolonged ventilation, 30-d readmissions, ICU readmission, number of ICU hours, hospitalization days after HT, or infections. This study demonstrates that DM and non-DM patients can achieve excellent glycemic control post-HT with IV and SQ insulin protocols with similar surgical outcomes and low hypoglycemia rates.

The teratogenic effect of dofetilide during rat limb development and association with drug-induced bradycardia and hypoxia in the embryo.

BACKGROUND: Dofetilide is an antiarrhythmic drug that blocks the cardiac repolarizing current IKr ((IKr, rapid component of the delayed rectifying potassium current). Previous studies have shown that (a) IKr is essential for normal cardiac function of the embryonic heart and (b) dofetilide is teratogenic in rodents. This study was undertaken to examine the mechanism by which dofetilide causes limb defects on gestational day 13 (GD 13) in the rat. METHODS: Rats were treated with dofetilide (single oral dose, 5 mg/kg) on GD 13 and embryonic heart rates assessed by ultrasound (Vevo770, VisualSonics, Toronto, Ontario, Canada) 2 hr later. Fetuses were examined for malformations on GD 20. In a separate experiment, dofetilide treatment of GD 13 rats was followed 2, 4, 12, or 24 hr with iv dosing with the hypoxia marker, pimonidazole (60 mg/kg). Embryos were collected and heart rates were assessed in vitro and hypoxia in embryo limbs analyzed. RESULTS: A teratogenic dose of dofetilide at a susceptible stage of development (GD 13) resulted in a period of bradycardia and arrhythmia of the embryonic heart and hypoxia in the developing limbs (GD 13) resulting in limb malformations (GD 20). CONCLUSIONS: Drugs that induce periods of bradycardia and/or arrhythmia of the embryonic heart and cause the embryo to become hypoxic are potential human teratogens.

The effect of prenatal exposure to a repeat high dose of toluene in the fetal rat.

Solvent abuse during pregnancy results in a clinical pattern of adverse outcomes including deafness. The aim of this project was to determine whether high doses of toluene for a short duration during pregnancy produced adverse outcomes in the fetal rat. Pregnant rats were given either 1250 mg/kg of toluene or peanut oil by gavage from gestation day 16-19. The study demonstrated that administration of toluene at the dose used did not result in significant maternal toxicity. However, some maternal renal pathology was noted. There was no significant difference in placental or fetal weights nor was there a significant difference in the number of external or skeletal malformations of fetuses between treatment and control groups. Treated fetuses had an increased frequency and severity of enlarged renal pelveses. A pattern of accelerated development in the upper mid-turn and sometimes apical turns in the treated fetal cochleas was observed. This accelerated development suggests that toluene may induce excessive cell death resulting in premature maturation of the cochlea.

Toxicity of landfill leachate to sea urchin development with a focus on ammonia.

Sea urchin gametes and embryos serve as a model system to evaluate toxicity in the marine environment. In this study, the toxicity of complex chemical mixtures in leachate samples to sea urchin development was examined with a focus on ammonia, which was the main contaminant of concern in most samples. Two rapid tests, the submitochondrial particle function and bacterial luminescence tests, were also used. Ammonia is highly toxic to sea urchin embryos with an EC50 of 1.3 mg l(-1) for the embryos of the Australian sea urchin Heliocidaris tuberculata. Leachate ammonia levels were well above these EC50 concentrations. To assess the contribution of ammonia to leachate toxicity in sea urchin development, we compared the predicted toxic units (PTU) and observed toxic units (OTU) for ammonia for each sample. The PTU/OTU comparison revealed that the sensitivity of the sea urchin embryos to ammonia were altered (enhanced or decreased) by other chemicals in the leachates. This result emphasises the need for parallel chemical analyses and a suite bioassays for evaluating the toxicity of complex and variable chemical mixtures.