Simplified hypertension screening approaches with low misclassification and high efficiency in the United States,Nepal, and India

Standard triplicate blood pressure (BP) measurements pose time barriers to hypertension screening, especially in resource‐limited settings. We assessed the implications of simplified approaches using fewer measurements with adults (≥18 years old) not using anti‐hypertensive medications from the US National Health and Nutrition Examination Survey 1999‐2016 (n = 30 614), and two datasets from May Measurement Month 2017‐2018 (n = 14 795 for Nepal and n = 6 771 for India). We evaluated the proportion of misclassification of hypertension when employing the following simplified approaches: using only 1st BP, only 2nd BP, 2nd if 1st BP in a given range (otherwise using 1st), and average of 1st and 2nd BP. Hypertension was defined as average of 2nd and 3rd systolic BP ≥140 and/or diastolic BP ≥90 mm Hg. Using only the 1st BP, the proportion of missed hypertension ranged from 8.2%–12.1% and overidentified hypertension from 4.3%–9.1%. Using only 2nd BP reduced the misclassification considerably (corresponding estimates, 4.9%–6.4% for missed hypertension and 2.0%–4.4% for overidentified hypertension) but needed 2nd BP in all participants. Using 2nd BP if 1st BP ≥130/80 demonstrated similar estimates of missed hypertension (3.8%–8.1%) and overidentified hypertension (2.0%–3.9%), but only required a 2nd BP in 33.8%–59.8% of participants. In conclusion, a simplified approach utilizing 1st BP supplemented by 2nd BP in some individuals has low misclassification rates and requires approximately half of the total number of measurements compared to the standard approach, and thus can facilitate screening in resource‐constrained settings.     

Severe diabetes and leptin resistance cause differential hepatic and renal transporter expression in mice

Background

Type-2 Diabetes is a major health concern in the United States and other Westernized countries, with prevalence increasing yearly. There is a need to better model and predict adverse drug reactions, drug-induced liver injury, and drug efficacy in this population. Because transporters significantly contribute to drug clearance and disposition, it is highly significant to determine whether a severe diabetes phenotype alters drug transporter expression, and whether diabetic mouse models have altered disposition of acetaminophen (APAP) metabolites.

Results

Transporter mRNA and protein expression were quantified in livers and kidneys of adult C57BKS and db/db mice, which have a severe diabetes phenotype due to a lack of a functional leptin receptor. The urinary excretion of acetaminophen-glucuronide, a substrate for multidrug resistance-associated proteins transporters was also determined. The mRNA expression of major uptake transporters, such as organic anion transporting polypeptide Slco1a1 in liver and kidney, 1a4 in liver, and Slc22a7 in kidney was decreased in db/db mice. In contrast, Abcc3 and 4 mRNA and protein expression was more than 2 fold higher in db/db male mouse livers as compared to C57BKS controls. Urine levels of APAP-glucuronide, -sulfate, and N-acetyl cysteine metabolites were higher in db/db mice.

Conclusion

A severe diabetes phenotype/presentation significantly altered drug transporter expression in liver and kidney, which corresponded with urinary APAP metabolite levels.     

Clinical experience with a new solvent detergent-treated intravenous immunoglobulin free of hypotensive effects

OBJECTIVE: To see if modifications to the processing of intravenous immunoglobulin to include a virus inactivation stage alter immunoglobulin G (IgG) resulting in hypotension in patients. METHODS: Clinical trials were done involving extensive patient monitoring during infusion: in vitro - testing for markers of hypotension, and in vivo - an animal model which closely simulates clinical use. RESULTS: No hypotensive response was seen in the animal model or clinical trial. CONCLUSIONS: The production process used does not damage IgG or create vaso-active kinins as the preparation was free of hypotensive effects.     

Factor XIIIA subunit and Crohn's disease.

Factor XIIIA is the active subunit of plasma factor XIII that is responsible for cross linking fibrin into a stable clot. Sixteen patients with Crohn's disease were studied prospectively from relapse (Crohn's disease activity index > 150) into remission. Plasma factor XIIIA concentrations were significantly lower in active disease (median 63 (95% CI 46-72) U/dl) than remission (median 90 (95% CI 60-112) U/dl; p = 0.002). Plasma factor XIIIA concentrations correlated positively with the activity index (p = 0.005) and platelet count (p = 0.003), and negatively with serum albumin (p = 0.006). In five patients with persistent aggressive disease, the factor XIIIA concentration remained below the lower range of normal despite apparent clinical improvement in response to medical treatment. Tissues from three patients who underwent surgical resection during the study were immunostained for factor XIIIA. Gut mucosal and submucosal macrophages stained strongly for factor XIIIA. In one patient, capillary thrombi near superficial mucosal erosions immunostained for factor XIIIA in macroscopically normal mucosa. Similar changes were identified in more severely inflamed sections of intestine from the other two patients. The demonstration of significantly low plasma factor XIIIA concentrations in active Crohn's disease, and the immunostaining of factor XIIIA in capillary thrombi in the bowel wall, suggest that activation of coagulation may be involved in the pathogenesis of Crohn's disease. The plasma factor XIIIA concentration may prove a useful laboratory marker of disease activity.     

Early mucosal changes in Crohn's disease.

Aphthoid ulceration has been regarded as an early macroscopic feature of Crohn's disease, yet the cause of this mucosal lesion is unknown. Examination of areas of apparently normal and non-inflamed bowel in Crohn's disease has allowed the identification of mucosal changes which occur before macroscopic and microscopic ulceration. Thirty five resection specimens from patients with Crohn's disease were compared with 12 specimens from patients with ulcerative colitis and 13 controls. Specimens were fixed either by immersion in formalin in the routine way or by perfusion fixation with formalin at mean arterial pressure. Immunostaining for macrophages, vessel wall, and blood constituents allowed identification of small mucosal capillaries which were not apparent otherwise. In Crohn's disease damage and rupture of these small capillaries occurred before infiltration of the lamina propria by inflammatory cells. Loss of the overlying epithelium seemed to follow this vascular damage.     

Lone atrial fibrillation and anticoagulant therapy

Assessment of risk of thromboembolism and potential benefit of prophylaxis with long-term anticoagulant therapy in lone atrial fibrillation is hampered by a lack of consensus regarding definition of lone atrial fibrillation. In general, patients less than 60 years of age with normal left ventricular function and left atrial size have a low risk of thromboembolic events and are unlikely to gain any significant benefit with anticoagulants; however, patients older than 60 years with impaired left ventricular function, enlarged left atrium, and/or associated conditions such as hypertension have an increased risk of thromboembolism and would benefit from long-term anticoagulant therapy. Decisions regarding anticoagulant usage would be simplified by using a scoring system containing clinical and investigational variables.     

A monoclonal antibody to human insulin-like growth factor-I: characterization, use in radioimmunoassay and effect on the biological activities of the growth factor

A monoclonal antibody (BPL-M23) to insulin-like growth factor-I (IGF-I) was obtained following immunization of BALB/c mice with human IGF-I conjugated to ovalbumin. The affinity constant of BPL-M23 for IGF-I was 10.5 litres/nmol and the cross-reactivities of IGF-II, multiplication-stimulating activity III-2 and insulin were 0.8, 0.03 and less than 0.0001% respectively. Porcine, bovine, ovine and rabbit sera, but not rat or mouse sera, showed substantial reactivity with the antibody. Comparison of radioimmunoassay analyses of 54 human serum samples from normal subjects and acromegalic and GH-deficient patients using BPL-M23 and a polyclonal rabbit antiserum (R557A) to human IGF-I showed a high correlation, indicating the usefulness of the monoclonal antibody in radioimmunoassay. Monoclonal antibody BPL-M23 was capable of abolishing the sulphation, mitogenic and insulin-like activities of IGF-I in in-vitro bioassays, suggesting that these activities may rely upon the same receptor-binding site which is near to the antibody-binding site.