Neuroglucopenia and Metabolic Distress in Two Patients with Viral Meningoencephalitis: A Microdialysis Study

Background

Cerebral edema is a major cause of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Arginine vasopressin (AVP) and water channel aquaporin-4 (AQP4) have been implicated in the pathogenesis of CA-evoked cerebral edema. In this study, we examined if conivaptan, a V_1a and V₂ antagonist, attenuates cerebral edema following CA/CPR in wild type (WT) mice as well as mice with targeted disruption of the gene encoding α-syntrophin (α-syn^?/?) that demonstrate diminished perivascular AQP4 pool.

Methods

Isoflurane-anesthetized adult male WT C57Bl/6 and α-syn^?/? mice were subjected to 8 min CA/CPR and treated with either bolus IV injection (0.15 or 0.3 mg/kg) followed by continuous infusion of conivaptan (0.15 mg/kg/day or 0.3 mg/kg/day), or vehicle infusion for 48 h. Serum osmolality, regional brain water content, and blood–brain barrier (BBB) disruption were determined at the end of the experiment. Sham-operated mice in both strains served as controls.

Results

Treatment with conivaptan elevated serum osmolality in a dose-dependent manner. In WT mice, conivaptan at 0.3 mg dose significantly attenuated regional water content in the caudoputamen (81.0 ± 0.5 vs 82.5 ± 0.4 % in controls; mean ± SEM) and cortex (78.8 ± 0.2 vs 79.4 ± 0.2 % in controls), while conivaptan at 0.15 mg was not effective. In α-syn^?/? mice, conivaptan at 0.3 mg dose did not attenuate water content compared with controls. Conivaptan (0.3 mg/kg/day) attenuated post-CA BBB disruption at 48 h in WT mice but not in α-syn^?/? mice.

Conclusions

Continuous IV infusion of conivaptan attenuates cerebral edema and BBB disruption following CA. These effects of conivaptan that are dependent on the presence of perivascular pool of AQP4 appear be mediated via its dual effect on V₁ and V₂ receptors.

     

Ethnic disparities: control of glycemia, blood pressure, and LDL cholesterol among US adults with type 2 diabetes

OBJECTIVE: To examine ethnic disparities in the quality of diabetes care among adults with diabetes in the US through a systematic qualitative review. DATA SOURCES: Material published in the English language was searched from 1993 through June 2003 using PubMed, Web of Science, Cumulative Index to Nursing and Allied Health, the Cochrane Library, Combined Health Information Database, and Education Resources Information Center. STUDY SELECTION AND DATA EXTRACTION: Studies of patients with diabetes in which at least 50% of study participants were ethnic minorities and studies that made ethnic group comparisons were eligible. Research on individuals having prediabetes, those <18 years of age, or women with gestational diabetes were excluded. Reviewers used a reproducible search strategy. A standardized abstraction and grading of articles for publication source and content were used. Data on glycemia, blood pressure, and low-density lipoprotein cholesterol (LDL-C) were extracted in patients with diabetes. A total of 390 studies were reviewed, with 78 meeting inclusion criteria. DATA SYNTHESIS: Ethnic minorities had poorer outcomes of care than non-Hispanic whites. These disparities were most pronounced for glycemic control and least evident for LDL-C control. Most studies showed blood pressure to be poorly controlled among ethnic minorities. CONCLUSIONS: Control of risk factors for diabetes (glycemia, blood pressure, LDL-C) is challenging and requires routine assessment. These findings indicate that additional efforts are needed to promote diabetes quality of care among minority populations.     

Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach

Introduction

We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia.

Methods

A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia.

Results

Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard^® and CoolLine^®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke.

Conclusion

In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result.     

Smoking and incidence of diabetes among U.S. adults: findings from the Insulin Resistance Atherosclerosis Study

OBJECTIVE: The objective of this study was to determine the association between smoking and incident diabetes among U.S. adults. RESEARCH DESIGN AND METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) was a prospective study of the associations of insulin sensitivity and cardiovascular risk factors. We examined the relationship between smoking status categories (never, former, and current) and incident 5-year type 2 diabetes among 906 participants free of diabetes at baseline. We also considered the effect of pack-year categories (never, former <20 pack-years, former > or = 20 pack-years, current <20 pack-years, and current > or = 20 pack-years) upon diabetes incidence. RESULTS: Of current smokers, 96 (25%) developed diabetes at 5 years, compared with 60 (14%) never smokers. After multivariable adjustment, current smokers exhibited increased incidence of diabetes compared with never smokers (odds ratio [OR] 2.66, P = 0.001). Similar results were found among current smokers with > or = 20 pack-years with normal glucose tolerance (5.66, P = 0.001). CONCLUSIONS: Smoking shares a robust association with incident diabetes, supporting the current Surgeon General's warnings against cigarette smoking.     

Deciphering the TLR transcriptome and downstream signaling pathway in cerebrospinal fluid in pediatric meningitis

Inflammation Research - Pediatric meningitis is characterized by a colossal inflammatory response to the pathogen in the central nervous system (CNS). This unabated inflammatory response persists...     

Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds

To anticipate to increased testing needs for reproductive toxicity and 3R approaches, we studied zebrafish embryo/larva as an alternative for animal testing for developmental toxicity and embryotoxicity and evaluated a training set of 27 compounds with a standardized protocol. The classification of compounds in the zebrafish embryo/larva assay, based on a prediction model using a TI (teratogenic index) cut-off value of 2, was compared to available animal and human data. When comparing the classification of compounds in the zebrafish embryo/larva assay to available animal classification, a sensitivity of 72% and specificity of 100% were obtained. The predictive values obtained in comparison to a limited set of human data were 50, 60% respectively for teratogens, non-teratogens. Overall, we demonstrated that the zebrafish embryo/larva assay, may be used as screening tool for prioritization of compounds and could contribute to reduction of animal experiments in the field of developmental toxicology.     

Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study

One hundred twenty-three children with intrauterine growth retardation were prospectively followed from birth to 9 to 10 years of age in order to characterize their specific neurodevelopmental and cognitive difficulties and to identify clinical predictors of such difficulties. Perinatal biometric data and risk factors were collected. Outcome was evaluated at age 9 to 10 by neurodevelopmental, cognitive, and school achievement assessments. Sixty-three children served as controls who were appropriate for gestational age. Significant differences in growth (P < .001), neurodevelopmental scores (P < .001), intelligence quotient (IQ) (P < .0001), and school achievements measured by the Kaufmann Assessment Battery for Children (P < .001) were found between the children with intrauterine growth retardation and controls. Children with intrauterine growth retardation demonstrated a specific profile of neurocognitive difficulties at school age, accounting for lower school achievements. The best perinatal parameter predictive of neurodevelopment and IQ was the Cephalization Index (P < .001). Somatic catch-up growth at age 2 and at age 9 to 10 correlated with favorable outcome at 9 to 10 years of age.     

Identification and sequence analysis of discordant phenotypes between AmpFlSTR SGM Plus™ and PowerPlex® 16

During duplicate analysis of buccal swabs from 1,377 individuals with 2 commercial short tandem repeat (STR) kits, we observed 8 discordant phenotypes with SGM Plus (SGM, second generation multiplex) for the STRs THO1 (2), vWA (4) and D18S51 (2), and 1 discrepancy with PowerPlex 16 for D18S51. One individual even showed two discrepancies (vWA and THO1) for SGM Plus. In each case, the difference observed was due to the non-amplification or allele dropout of the second allele in a heterozygous genotype. Sequence analysis revealed each time the presence of a mutation that probably coincided with the primer-binding site. Primer-binding site mutations for vWA and D18S51 have been reported previously, while the mutation for THO1 (C-to-T substitution at position 1286 of GenBank sequence D00269) is reported here for the first time. While the frequency of these silent alleles remains low (0.58% in our study), it is suggested that appropriate measures should be taken for database comparisons and that allelic dropout should be further investigated by sequence analysis and be reported to the forensic community.