Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

Aims/hypothesis. We have previously shown that lactate protects brain function during insulin-induced hypoglycaemia. An adaptation process could, however, not be excluded because the blood lactate increase preceded hypoglycaemia.¶Methods. We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mU · kg^–1· min^–1) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmo/l) with and without Na-lactate infusion (30 μmol · kg^–1· min^–1) given after initiation of hypoglycaemic symptoms.¶Results. The glucose threshold for epinephrine response was similar (control subjects 3.2 ± 0.1 vs 3.2 ± 0.1, diabetic patients = 3.5 ± 0.1 vs 3.5 ± 0.1 mmol/l) in both studies. The magnitude of the response was, however, blunted by lactate infusion (AUC; control subjects 65 ± 28 vs 314 ± 55 nmol/l/180 min, zenith = 2.6 ± 0.5 vs 4.8 ± 0.7 nmol/l, p < 0.05; diabetic patients = 102 ± 14 vs 205 ± 40 nmol/l/180 min, zenith = 1.4 ± 0.4 vs 3.2 ± 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C = autonomic 3.0 ± 0.1 vs 3.0 ± 0.1, neuroglycopenic = 2.8 ± 0.1 vs 2.9 ± 0.1 mmol/l, D = autonomic 3.2 ± 0.1 vs 3.2 ± 0.1, neuroglycopenic 3.1 ± 0.1 vs 3.2 ± 0.1 mmol/l) but peak responses were significantly attenuated by lactate (score at 160 min C = 2.6 ± 1 vs 8.8 ± 1, and 0.4 ± 0.4 vs 4.8 ± 1, respectively; p = 0.02–0.01, D = 1.3 ± 0.5 vs 6.3 ± 1.7, and 2.3 ± 0.6 vs 5.7 ± 1.1 p = 0.07–0.02). Cognitive function deteriorated in both studies at similar glucose thresholds (C = 3.1 ± 0.1 vs 3.0 ± 0.1, D = 3.2 ± 0.1 vs 3.3 ± 0.2 mmol/l). Although in normal subjects a much smaller impairment was observed with lactate infusion (Δ four-choice reaction time at 160 min = 22 ± 12 vs 77 ± 31 ms; p = 0.02), in Type I diabetic patients lactate infusion was associated with an improvement in cognitive dysfunction (0.2 ± 0.4 vs –38 ± 0.2 Δ ms, p = 0.0001).¶Conclusion/interpretation. A blood lactate increase after the development of hypoglycaemic symptoms reduces counterregulatory and symptomatic responses to insulin-induced hypoglycaemia and favours brain function rescue both in normal and diabetic subjects. These findings confirm that lactate is an alternative substrate to glucose for cerebral metabolism under hypoglycaemic conditions. [Diabetologia (2000) 43: 733–741]     

Cross‐Sectional Study of Respiratory Symptoms,Spirometry, and Immunologic Sensitivity in Epoxy Resin Workers

Objectives

An epoxy resin worker developed hypersensitivity pneumonitis requiring lung transplantation and had an abnormal blood lymphocyte proliferation test (LPT) to an epoxy hardener. We assessed the prevalence of symptoms, abnormal spirometry, and abnormal epoxy resin LPT results in epoxy resin workers compared to unexposed workers.

Methods

Participants completed questionnaires and underwent spirometry. We collected blood for epoxy resin LPT and calculated stimulation indices for five epoxy resin products.

Results

We compared 38 exposed to 32 unexposed workers. Higher exposed workers were more likely to report cough (OR 10.86, [1.23‐infinity], p = 0.030) or wheeze (OR 4.44, [1.00‐22.25], p = 0.049) than unexposed workers, even controlling for smoking. Higher exposed workers were more likely to have abnormal FEV1 than unexposed workers (OR 10.51, [0.86‐589.9], p = 0.071), although not statistically significant when adjusted for smoking. There were no differences in proportion of abnormal epoxy resin system LPTs between exposed and unexposed workers.

Conclusions

In summary, workers exposed to epoxy resin system chemicals were more likely to report respiratory symptoms and have abnormal FEV1 than unexposed workers. Use of epoxy resin LPT was not helpful as a biomarker of exposure and sensitization.     

Guidelines for prevention of hospital acquired infections

These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.     

Is cognitive behaviour therapy of benefit for melancholic depression?

Objective

This paper seeks to determine the relevance and likely salience of cognitive behaviour therapy (CBT) as a treatment for melancholic depression.

Methods

The findings of a randomised trial comparing 12-week outcome of 18 patients with melancholic depression receiving antidepressant medication and 11 receiving CBT were evaluated, and qualitative explanations for the outcomes were provided principally by the treating CBT practitioners.

Results

In the trial, CBT showed no improvement in depression severity in the first four weeks and then some level of improvement over the subsequent eight weeks. Outcome was superior for those receiving antidepressant medication at 12 weeks and was first demonstrated at four weeks. The benefits of CBT appeared to be in settling anxiety, dealing with cognitive processing of having a melancholic depression and addressing any personality vulnerabilities.

Conclusion

While a pilot study, our qualitative reports indicate that CBT may provide a useful role in managing melancholia as an adjunct to antidepressant medication. Future studies examining such a combination treatment model should seek to determine if indicative data provided here argue for a sequencing model of CBT being introduced after medication has addressed core biological underpinnings.     

Factors associated with encephalopathy in patients with Salmonella enterica serotype Typhi bacteremia presenting to a diarrheal hospital in Dhaka, Bangladesh

To characterize clinical correlates of typhoid fever-associated encephalopathy, we performed a retrospective chart review of patients with Salmonella enterica serotype Typhi bacteremia who were hospitalized at the International Centre for Diarrhoeal Disease Research, Bangladesh, from February of 2009 to June of 2011. Of 207 patients bacteremic with Salmonella Typhi who were ≥ 5 years of age, we identified 43 (21%) patients with encephalopathy. Univariate analysis revealed that patients with encephalopathy more often presented at ages of 10-24 years and had severe dehydration, low oxygen saturation, high respiratory rate, low leukocyte count, low platelet count, and Widal flagellar H agglutinin (TH) titer ≥ 1:640 compared with typhoid patients without encephalopathy. Multivariate analysis using logistic regression showed that age, dehydration, leukocyte count, and Widal TH titer were independently associated with encephalopathy. Our findings suggest that age, severity of disease, and immune responses are associated with encephalopathy during Salmonella Typhi bacteremia, perhaps reflecting the impact of prominent inflammatory responses.     

Lifestyle risk factors predict disability and death in healthy aging adults

BackgroundAssociations between modifiable health risk factors during middle age with disability and mortality in later life are critical to maximizing longevity while preserving function. Positive health effects of maintenance of normal weight, routine exercise, and nonsmoking are known for the short and intermediate term. We studied the effects of these risk factors into advanced age.MethodsA cohort of 2327 college alumnae aged 60 years or more was followed annually (1986-2005) by questionnaires addressing health risk factors, history, and Health Assessment Questionnaire disability. Mortality data were ascertained from the National Death Index. Low-, medium-, and high-risk groups were created on the basis of the number (0, 1, ≥2) of health risk factors (overweight, smoking, inactivity) at baseline. Disability and mortality for each group were estimated from unadjusted data and regression analyses. Multivariable survival analyses estimated time to disability or death.ResultsThe medium- and high-risk groups had higher disability than the low-risk group throughout the study (P < .001). Low-risk subjects had onset of moderate disability delayed 8.3 years compared with high-risk subjects. Mortality rates were higher in the high-risk group (384 vs 247 per 10,000 person-years). Multivariable survival analyses showed the number of risk factors to be associated with cumulative disability and increased mortality.ConclusionSeniors with fewer behavioral risk factors during middle age have lower disability and improved survival. These data document that the associations of lifestyle risk factors on health continue into the ninth decade.