Topical tacrolimus therapy in the management of lower extremity ulcers due to prolidase deficiency

Prolidase deficiency is a rare autosomal recessive disorder characterized by cutaneous ulcers, facial dysmorphism, recurrent infections, and intellectual disability. We report a unique case of a 6‐year‐old boy with prolidase deficiency and Crohn's disease who presented with lower extremity ulcers. Cutaneous ulcers due to prolidase deficiency are historically resistant to treatment, and we report success with the novel use of topical tacrolimus.     

Clinical outcomes of bypass-first versus endovascular-first strategy in patients with chronic limb-threatening ischemia due to infrageniculate arterial disease

Background

Chronic limb-threatening ischemia (CLTI), defined as ischemic rest pain or tissue loss secondary to arterial insufficiency, is caused by multilevel arterial disease with frequent, severe infrageniculate disease. The rise in CLTI is in part the result of increasing worldwide prevalence of diabetes, renal insufficiency, and advanced aging of the population. The aim of this study was to compare a bypass-first with an endovascular-first revascularization strategy in patients with CLTI due to infrageniculate arterial disease.

The effect of bracing on proprioception of knees with anterior cruciate ligament injury.

This paper is a comprehensive review on the effect of bandaging, bracing, and neoprene sleeves on knee proprioception following anterior cruciate ligament (ACL) injury and reconstruction with a focus on studies that have measured joint position sense and threshold to detection of passive knee motion. Disruption of the ACL does not appear to alter joint position sense soon after injury, although there is evidence that in some subjects deterioration may occur over time. An ACL tear creates a deficit in the threshold to detection of passive knee motion soon after injury and in those with chronic tears. The magnitude of worsening is less then 1.0 degree of movement in flexion-extension and of questionable concern from a clinical and functional perspective. Application of a functional brace or neoprene sleeve to the ACL-deficient limb does not improve the threshold to detection of passive knee motion; however, application of an elastic bandage to a knee with an ACL tear improves joint position sense. Reconstruction of a torn ACL is associated with a deficit in the threshold to detection of passive knee motion, and during the first year of healing the use of a neoprene sleeve provides improvement. Two years following ACL reconstruction there is no deficit in the threshold to detection of passive knee motion and the use of a brace has no effect on this outcome.     

Engineering human immunodeficiency virus 1 protease heterodimers as macromolecular inhibitors of viral maturation.

Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disruption of the dimer interface inhibits this activity as does formation of heterodimers between wild-type and defective monomers. A structure-based approach was used to identify amino acid substitutions at the dimer interface of HIV-1 PR that facilitate preferential association of heterodimers and inhibit self-association of the defective monomers. Expression of the designed PR monomers inhibits activity of wild-type HIV-1 PR and viral infectivity when assayed in an ex vivo model system. These results show that it is possible to design PR monomers as macromolecular inhibitors that may provide an alternative to small molecule inhibitors for the treatment of HIV infection.     

Determination of D-sorbitol in human erythrocytes by an improved enzymatic method with fluorometric detection

In this enzymatic method to analyze erythrocytes for D-sorbitol, the erythrocytes were separated from plasma by centrifugation, washed with isotonic saline (9 g/L NaCl), then diluted threefold with more saline. We lysed 1.5 mL of the diluted erythrocytes with chloroform and precipitated the protein with 58 g/L HClO4 solution. The resulting supernates were mixed with buffer, NAD+, and sorbitol dehydrogenase (EC 1.1.1.14). For standards, we added sorbitol to the erythrocytes before lysing. After 25 min of incubation at 37 degrees C, the fluorescence responses were recorded. Results for sorbitol were corrected for sample-blank and enzyme fluorescence, and were then normalized for hemoglobin content. Response was linear for a sorbitol concentration range of 1 to 30 mumol/L. Reproducibility was good, with an average CV of 2.5% at 10 mumol/L. Results for healthy individuals and diabetic patients are presented.