Gaps in Serologic Immunity against Contemporary Swine-Origin Influenza A Viruses among Healthy Individuals in the United States

Influenza A Viruses (IAV) in domestic swine (IAV-S) are associated with sporadic zoonotic transmission at the human–animal interface. Previous pandemic IAVs originated from animals, which emphasizes the importance of characterizing human immunity against the increasingly diverse IAV-S. We analyzed serum samples from healthy human donors (n = 153) using hemagglutination-inhibition (HAI) assay to assess existing serologic protection against a panel of contemporary IAV-S isolated from swine in the United States (n = 11). Age-specific seroprotection rates (SPR), which are the proportion of individuals with HAI ≥ 1:40, corresponded with lower or moderate pandemic risk classifications for the multiple IAV-S examined (one H1-δ1, one H1-δ2, three H3-IVA, one H3-IVB, one H3-IVF). Individuals born between 2004 and 2013 had SPRs of 0% for the five classified H3 subtype IAV-S, indicating youth may be particularly predisposed to infection with these viruses. Expansion of existing immunologic gaps over time could increase likelihood of future IAV-S spillover to humans and facilitate subsequent sustained human-to-human transmission resulting in disease outbreaks with pandemic potential.     

Reaching a shared understanding of shared decision making in health care: NICE's experience of scoping the shared decision making guideline

NICE's guideline on shared decision making, currently under development, endeavours to support shared decision making as part of routine health care practice. In this article, we summarize our learning to date, gained through the scoping of the guideline, on the key challenges that need to be addressed in the guideline. The production of a scope is the first stage in the development of a NICE guideline, setting the parameters for what will be considered in the guideline. The process for scoping the shared decision making guideline involved discussion with early recruited committee members and engagement with registered stakeholders, through both a workshop and formal consultation. Important, and sometimes divergent, viewpoints about shared decision making were revealed through this process. The key challenges centred on the issues of a need for a common definition of shared decision making, measurability, opportunities, barriers to implementation, and feasibility. Recognizing these challenges aided the refinement of the scope in terms of what the guideline will cover, draft questions and main outcomes for consideration.     

Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death

We have proposed the "glucolipotoxicity" hypothesis in which elevated free fatty acids (FFAs) together with hyperglycemia are synergistic in causing islet beta-cell damage because high glucose inhibits fat oxidation and consequently lipid detoxification. The effects of 1-2 d culture of both rat INS 832/13 cells and human islet beta-cells were investigated in medium containing glucose (5, 11, 20 mM) in the presence or absence of various FFAs. A marked synergistic effect of elevated concentrations of glucose and saturated FFA (palmitate and stearate) on inducing beta-cell death by apoptosis was found in both INS 832/13 and human islet beta-cells. In comparison, linoleate (polyunsaturated) synergized only modestly with high glucose, whereas oleate (monounsaturated) was not toxic. Treating cells with the acyl-coenzyme A synthase inhibitor triacsin C, or the AMP kinase activators metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside that redirect lipid partitioning to oxidation, curtailed glucolipotoxicity. In contrast, the fat oxidation inhibitor etomoxir, like glucose, markedly enhanced palmitate-induced cell death. The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. The results support the glucolipotoxicity hypothesis of beta-cell failure proposing that elevated FFAs are particularly toxic in the context of hyperglycemia.     

Mechanism of suppression of renin secretion by clonidine in the dog

The mechanism by which clonidine suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which renal perfusion pressure was controlled by means of an aortic clamp. Clonidine (30 microgram/kg, iv) lowered mean arterial pressure (MAP) from 124 +/- 8 to 104 +/- 4 mm Hg (P less than 0.01) and reduced plasma renin activity (PRA) to 32 +/- 4 percent of the control value (P less than 0.01) after 60 minutes. Ganglion blockade with pentolinium (3 mg/kg, im) decreased MAP from 148+/- 7 to 117 +/- 3 mm Hg (P less than 0.01) and reduced PRA to 55 +/- 13 percent of the control value (P less than 0.05) after 45 minutes. Pentolinium converted the hypotension produced by clonidine to hypertension (108 +/- 9 to 146 +/- 10 mm Hg at 60 minutes, P less than 0.05) and abolished the suppression of PRA (105 +/- 14 percent of control at 60 minutes, P less than 0.05). In a further series of experiments, the effects of oxymetazoline, an alpha-adrenergic receptor agonist which is closely related to clonidine but which does not cross the blood brain barrier, were studied. Oxymetazoline (10 microgram/kg, iv) increased MAP from 127 +/- 3 to 154 +/- 2 mm Hg (P less than 0.01) and elevated PRA TO 176 +/- 22 percent of the control value (P less than 0.02) after 30 minutes. A higher dose of oxymetazoline (30 microgram/kg) increased MAP from 129 +/- 10 to 161 +/- 9 mm Hg (P less than 0.05) and increased PRA to 256+/- 37 percent of control (P less than 0.05) after 30 minutes. Taken together, these data support the hypothesis that the inhibition of renin secretion by clonidine results from a centrally mediated decrease in sympathetic neural activity.     

Alteration of pulmonary function in intravenous drug abusers: Prevalence,severity, and characterization of gas exchange abnormalities

We examined the influence of chronic intravenous drug abuse on respiratory function in 512 consecutive drug addicts by obtaining respiratory histories, pulmonary function tests and chest roentgenograms. Two hundred and fourteen (42 per cent) had carbon monoxide-diffusing capacities (D_lco) of < 75 per cent predicted (mean 65.7 per cent), and in 38 per cent reduced D_lco was the sole pulmonary function test abnormality. Obstructive lung disease attributed to asthma or chronic bronchitis was observed in 6 per cent and a restrictive defect due to interstitial lung disease was observed in 7 per cent. Exercise limitation due to dyspnea among those patients with altered pulmonary function was uncommon except in those with obstructive or restrictive lung disease. Roentgenographic evidence of pulmonary hypertension was not observed in any of the patients. Gas exchange measured at rest and during exercise in 11 patients with a low D_lco and in three patients with restrictive lung disease and a low D_lco revealed an increased alveolar-arterial oxygen difference but normal minute ventilation, dead space-to-tidal volume ratio and absence of abnormal right-to-left shunts. We conclude that alterations in pulmonary function in drug addicts due to foreign particle emboli are very common but that significant respiratory symptoms are unusual and that abnormalities in gas exchange during exercise are mild.     

Transient insulin increase in reactive hypoglycemia in obese and non-obese subjects

(1). Insulin levels at the moment of glucose-induced reactive hypoglycemia have been compared with zero-hour insulin levels in 108 subjects in whom the blood glucose had decreased to 50 mg percent or less (50 to 31 mg) at the third, fourth, or fifth hour in the course of an oral glucose tolerance test (1.75 g/kg of body weight). (2). Of the 47 obese subjects, insulin levels at the time of the reactive hypoglycemia were inappropriately high, ie exceeded the fasting insulin level by 20 uU/ml or more in 38 percent and by 40 microunits/ml or higher in 26 percent of the tests. (3). In 61 non-obese subjects, employing the same criteria, inappropriately high insulinemia at the time of reactive hypoglycemia was recorded with about the same frequency. (4). In each instance of reactive hypoglycemia of 50 mg percent or less with concomitant insulin levels above the starting value to the degree stipulated, the so-termed inappropriate hyperinsulinemia was transient. In other words, judging by levels preceding and/or following the reactive hypoglycemia, insulin titers were decreasing and hence, the inappropriately high insulin level at the moment of hypoglycemia represented a lag phenomenon. (5). The above data suggest that insulin levels elevated above the starting value may play a role in reactive hypoglycemia. In subjects with insulin levels at the time of reactive hypoglycemia equal to or below the starting value, the low blood glucose level cannot be attributed to insulin. In such instances, delay or lag in hepatic glucose output and/or counter-regulatory responses probably play the dominant or sole role in the reactive hypoglycemia.     

Cultural case management of latent tuberculosis infection.

SETTING: The proportion of tuberculosis (TB) among foreign-born individuals in the United States is steadily increasing. Treatment of latent TB infection can prevent future cases of disease, although generally only 60% of patients who start a 6-month regimen of isoniazid complete therapy. OBJECTIVE: Cultural case management--employing case manager cultural mediators who serve patient-defined needs in addition to performing TB control functions--may improve results of testing and treatment in one high-risk group, new refugees. DESIGN: A cultural case management approach was established for finding and treating latent TB infection among three groups of new refugees: from the former Soviet Union (FSU), former Yugoslavia (FY), and Somalia. RESULTS: From July 1999 through December 2000, treatment was offered to 442 refugees, of whom 389 (88%) started and 319 (82%) completed therapy. The completion rate among starters from the FSU was 76%, for those from FY it was 94% and for those from Somalia it was 88%. Among all refugees to whom treatment was offered, 319/442 (72%) completed therapy. CONCLUSION: Cultural case management may be a useful tool for expanding treatment of latent TB infection among foreign-born individuals.