Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index

OBJECTIVE: To evaluate the clinical/research utility of the low blood glucose index (LBGI), a measure of the risk of severe hypoglycemia (SH), based on self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODS: There were 96 adults with IDDM (mean age 35+/-8 years, duration of diabetes 16+/-10 years, HbA1 8.6+/-1.8%), 43 of whom had a recent history of SH (53 did not), who used memory meters for 135+/-53 SMBG readings over a month, and then for the next 6 months recorded occurrence of SH. The SMBG data were mathematically transformed, and an LBGI was computed for each patient. RESULTS: The two patient groups did not differ with respect to HbA1, insulin units per day, average blood glucose (BG) and BG variability. Patients with history of SH demonstrated a higher LBGI (P < 0.0005) and a trend to be older with longer diabetes duration. Analysis of odds for future SH classified patients into low- (LBGI <2.5), moderate- (LBGI 2.5-5), and high- (LBGI >5) risk groups. Over the following 6 months low-, moderate-, and high-risk patients reported 0.4, 2.3, and 5.2 SH episodes, respectively (P = 0.001). The frequency of future SH was predicted by the LBGI and history of SH (R2 = 40%), while HbA1, age, duration of diabetes, and BG variability were not significant predictors. CONCLUSIONS: LBGI provides an accurate assessment of risk of SH. In the traditional relationship history of SH-to-future SH, LBGI may be the missing link that reflects present risk. Because it is based on SMBG records automatically stored by many reflectance meters, the LBGI is an effective and clinically useful on-line indicator for SH risk.     

An eukaryotic RuvB-like protein (RUVBL1) essential for growth

A human protein (RUVBL1), consisting of 456 amino acids (50 kDa) and highly homologous to RuvB, was identified by using the 14-kDa subunit of replication protein A (hsRPA3) as bait in a yeast two-hybrid system. RuvB is a bacterial protein involved in genetic recombination that bears structural similarity to subunits of the RF-C clamp loader family of proteins. Fluorescence in situ hybridization analysis demonstrated that the RUVBL1 gene is located at 3q21, a region with frequent rearrangements in different types of leukemia and solid tumors. RUVBL1 co-immunoprecipitated with at least three other unidentified cellular proteins and was detected in the RNA polymerase II holoenzyme complex purified over multiple chromatographic steps. In addition, two yeast homologs, scRUVBL1 and scRUVBL2 with 70 and 42% identity to RUVBL1, respectively, were revealed by screening the complete Saccharomyces cerevisiae genome sequence. Yeast with a null mutation in scRUVBL1 was nonviable. Thus RUVBL1 is an eukaryotic member of the RuvB/clamp loader family of structurally related proteins from bacteria and eukaryotes that is essential for viability of yeast.     

Tissue reactions to bacteria-challenged implantable leads with enhanced infection resistance

Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin. The insulating polyurethane tubing material of the leads was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. Implantation periods varied from day 4, to week 3 1/2, to week 10. We investigated tissue reactions in the absence of an infectious challenge and also the efficacy of surface-modified leads in preventing infection after challenge with Staphylococcus aureus was evaluated. It was demonstrated that the applied surface modification did not induce adverse effects although during early postimplantation an increase in infiltration of granulocytes and macrophages and wound fluid and fibrin deposition were observed. After bacterial challenge, standard leads were heavily infected at each explantation period, denoted by abscesses, cellular debris, and bacterial colonies. In contrast, little or no infection was observed, either macroscopically or by bacterial cultures, with the surface-modified leads. Microscopy showed little evidence of the bacterial challenge, and that primarily at day 4. It was concluded that the applied surface modification demonstrated enhanced infection resistance and thus represents a sound approach to the battle against infectious complications with biomaterials.     

Separate jasmonate-dependent and salicylate-dependent defense-response pathways in Arabidopsis are essential for resistance to distinct microbial pathogens

The endogenous plant hormones salicylic acid (SA) and jasmonic acid (JA), whose levels increase on pathogen infection, activate separate sets of genes encoding antimicrobial proteins in Arabidopsis thaliana. The pathogen-inducible genes PR-1, PR-2, and PR-5 require SA signaling for activation, whereas the plant defensin gene PDF1.2, along with a PR-3 and PR-4 gene, are induced by pathogens via an SA-independent and JA-dependent pathway. An Arabidopsis mutant, coi1, that is affected in the JA-response pathway shows enhanced susceptibility to infection by the fungal pathogens Alternaria brassicicola and Botrytis cinerea but not to Peronospora parasitica, and vice versa for two Arabidopsis genotypes (npr1 and NahG) with a defect in their SA response. Resistance to P. parasitica was boosted by external application of the SA-mimicking compound 2, 6-dichloroisonicotinic acid [Delaney, T., et al. (1994) Science 266, 1247-1250] but not by methyl jasmonate (MeJA), whereas treatment with MeJA but not 2,6-dichloroisonicotinic acid elevated resistance to Alternaria brassicicola. The protective effect of MeJA against A. brassicicola was the result of an endogenous defense response activated in planta and not a direct effect of MeJA on the pathogen, as no protection to A. brassicicola was observed in the coi1 mutant treated with MeJA. These data point to the existence of at least two separate hormone-dependent defense pathways in Arabidopsis that contribute to resistance against distinct microbial pathogens.     

Update on implantable cardioverter-defibrillators. New, safer devices have led to changes in indications

The safety and efficacy of ICDs have improved significantly in the past few years. Recent evidence supports the value of these devices not only for secondary prevention of sudden cardiac death, but also for primary prevention in post-myocardial infarction patients with poor left ventricular function, unsustained ventricular tachycardia, and inducible ventricular tachycardia on electrophysiologic study. Transvenous defibrillation using the defibrillator case as the high-voltage electrode and a biphasic shock is currently the procedure of choice. Implantation is simple, and the defibrillation thresholds are acceptably low. However, the possibility of interactions must be considered in patients with cardiac pacemakers.     

Disabilities of arithmetic and mathematical reasoning: perspectives from neurology and neuropsychology

Current research on brain-behavior relationships in disabilities of arithmetic and mathematical reasoning is reviewed from both a neurological and a neuropsychological perspective. Although no entirely satisfactory statement of the relationship between arithmetic skills and brain functions has yet emerged, investigators in this area have provided evidence regarding the involvement of some brain systems in processes of calculation. Also, the developmental importance of right- versus left-hemisphere integrity for the mediation of arithmetic learning and performance has been suggested. We propose that an account of brain-behavior relationships in children intended to explain and predict developmental disabilities of arithmetic learning needs to address several important content and processing distinctions in order to (a) encompass empirically derived subtypes of children with learning disabilities who exhibit difficulties with arithmetic and (b) provide adequate direction for future subtyping and intervention research.     

Impaired pancreatic polypeptide release to insulin hypoglycaemia in chronic autonomic failure with postural hypotension: evidence for parasympathetic dysfunction

1. Release of pancreatic polypeptide (PP) is largely under vagal control and measurement of change in PP after insulin hypoglycaemia offers a non-invasive method of assessing vagal activity. 2. Changes in blood sugar and PP after intravenous insulin (0.2 unit/kg) were examined in six patients with idiopathic chronic autonomic failure (AF) and 12 control subjects. Six of the controls were studied before and after atropine treatment. 3. The PP levels in controls rose from 32 +/- 9 (mean +/- SEM) to 236 +/- 54 pmol/l after 45 min. Patients had similar baseline values (23 +/- 5 pmol/l) but a markedly reduced and delayed PP response to hypoglycaemia (49 +/- 19 pmol/l at 90 min). This impaired PP response was similar to that seen in controls after atropine. 4. The impaired PP response to insulin hypoglycaemia in patients with AF strongly suggests a dysfunction of vagal activity which is often clinically inapparent.     

Recurrent unexplained syncope: the role of head-upright tilt table testing

Recurrent episodes of sudden unexplained syncope are a common complaint of patients referred to health care professionals for evaluation. Traditional evaluations are both time consuming and expensive and leave many patients without a diagnosis. Although vasovagally mediated episodes of hypotension and bradycardia have been thought to be a common cause of unexplained syncope, this was traditionally a diagnosis of exclusion. Head-upright tilt table testing has recently emerged as a valuable method for confirming the diagnosis of vasovagal syncope and has allowed a better understanding of this phenomena. This article reviews the pathophysiology of vasovagal syncope, the use of head-upright tilt table testing in its diagnosis, and potential therapies used to prevent recurrences.