Unexpected antibody against the high-prevalence P antigen before cardiac surgery.

P is a high-prevalence antigen present in 99.9 percent of the population and is fully developed at birth. P- individuals form naturally occurring antibodies against P, which are often of immunoglobulin (Ig)M and/or IgG type, very potent in complement activation, and able to cause serious intravascular hemolytic transfusion reactions. Some people with anti-P have the rare P1 k phenotype, which lacks P in the presence of P1 and Pk. Blood transfusion in patients with anti-P is challenging, as is described here. A male patient without a history of blood transfusion was admitted for a planned cardiac surgery. The preoperative ABO blood group could not be determined because of unexpected reactions in the reverse grouping, and all red blood cells (RBCs) in the antibody detection test were positive, except for the autocontrol. Further analysis of the patient's sample confirmed the presence of the P1 k phenotype, and anti-P was identified. If transfusion was needed, P- blood would be required, and the only P- RBCs available were at the national Sanquin Bank of Frozen Blood. These units are limited, expensive, and only available for 48 hours after thawing. In the case of massive blood loss, first ABO and Rh-compatible units should be transfused, followed by P- units after the bleeding stops. In our case, the surgery was conducted without transfusion. This case illustrates the importance of preoperative ABO blood group testing and antibody screening in cases where blood loss can be expected. In recent years, more focus has been put on patient blood management. A good collaboration between the local laboratory, surgery department, and dedicated blood transfusion laboratory is critical to prevent unnecessary incompatible blood transfusions with potentially serious outcomes.

Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS)-pilot evaluation of a simple point-of-care ultrasound protocol and short training program for detecting urinary tract morbidity in highly endemic settings.

BACKGROUND: Urogenital schistosomiasis (UGS) causes inflammation and fibrosis of the urinary tract. In resource-limited settings, affordable tools for morbidity assessment in clinical care are needed. Point-of-care ultrasound has not yet been validated for UGS-related pathology. METHODS: We developed a protocol for Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS), assessing pathology of the bladder wall, ureters and kidneys. Following standardized training, two clinicians performed FASUS on children and adults with hematuria in Lambaréné, Gabon. Recorded ultrasound clips were remotely reviewed by two ultrasound experts as a diagnostic reference. RESULTS: In 2015 and 2016, scans were performed in 118 patients. The image quality was sufficient in 90% of bladder views and more than 97% of kidney views. UGS-compatible pathology was detected in 51/118 (43%) by the operator and in 46/107 (43%) by the experts among baseline scans of sufficient quality. Inter-rater agreement between operators and experts was very good (κ > 0.8) for hydronephrosis and good (κ > 0.6) for bladder wall thickening. CONCLUSIONS: FASUS is a promising clinical, point-of-care tool for detecting UGS-related urinary tract morbidity in symptomatic patients. Based on larger validation studies, appropriate diagnostic and therapeutic algorithms for the use of FASUS should be established.

The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system.

BACKGROUND AND PURPOSE: Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro. EXPERIMENTAL APPROACH: Male C57Bl/6J mice were fed a run-in high-fat diet for 6 weeks, before receiving topiramate or vehicle mixed in high-fat diet for an additional 6 weeks. Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamp. The extent to which the insulin sensitizing effects of topiramate were mediated through the CNS were determined by concomitant i.c.v. infusion of vehicle or tolbutamide, an inhibitor of ATP-sensitive potassium channels in neurons. The direct effects of topiramate on insulin signalling and glucose uptake were assessed in vivo and in cultured muscle cells. KEY RESULTS: In hyperinsulinaemic-euglycaemic clamp conditions, therapeutic plasma concentrations of topiramate (∼4 µg·mL(-1) ) improved insulin sensitivity (glucose infusion rate + 58%). Using 2-deoxy-D-[(3) H]glucose, we established that topiramate improved the insulin-mediated glucose uptake by heart (+92%), muscle (+116%) and adipose tissue (+586%). Upon i.c.v. tolbutamide, the insulin-sensitizing effect of topiramate was completely abrogated. Topiramate did not directly affect glucose uptake or insulin signalling neither in vivo nor in cultured muscle cells. CONCLUSION AND IMPLICATIONS: In conclusion, topiramate stimulates insulin-mediated glucose uptake in vivo through the CNS. These observations illustrate the possibility of pharmacological modulation of peripheral insulin resistance through a target in the CNS.