Non-union and use of proton pump inhibitors in the treatment of femoral and tibial shaft fractures: a nested case–control study

European Journal of Orthopaedic Surgery & Traumatology - Proton pump inhibitors (PPIs) are one of the most frequently used drugs worldwide. Previous research has shown that they could increase...     

Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1

The insulinotropic agent, exendin-4, is a long-acting analogue of glucagon-like peptide-1 (GLP-1) which improves glucose tolerance in humans and animals with diabetes, but the underlying mechanisms and the effects of exendin-4 on peripheral (muscle/fat) insulin action are unclear. Previous in vivo and clinical studies have been difficult to interpret because of complex, simultaneous changes in insulin and glucagon levels and possible effects on hepatic metabolism. Thus, the comparative effects of exendin-4 and GLP-1 on insulin-stimulated 2-[3H]deoxyglucose (2-DOG) uptake were measured in fully differentiated L6 myotubes and 3T3-adipocytes, including co-incubation with inhibitors of the PI-3-kinase (wortmannin) and mitogen-activated protein (MAP) kinase (PD098059) pathways. In L6 myotubes, there was a concentration-dependent and PI-3-kinase-dependent increase in insulin-stimulated 2-DOG uptake with exendin-4 and GLP-1, e.g. for exendin-4 the C(I-200) value (concentration of insulin required to increase 2-DOG uptake 2-fold) decreased from 1.3 +/- 1.4 x 10(-7)M (insulin alone, n=16) to 5.9 +/- 1.3 x 10(-8)M (insulin+exendin-4 0.1nM, n=18, P<0.03). A similar insulin-sensitizing effect was observed with exendin-4 in 3T3-adipocytes, but GLP-1 had no effect on adipocyte insulin sensitivity. In conclusion, this is the first direct evidence showing that exendin-4 increases insulin-stimulated glucose uptake in muscle and fat derived cells via a pathway that involves PI-3-kinase activation. Furthermore, the contrasting responses of exendin and GLP-1 in 3T3-adipocytes suggest that the peripheral insulin-sensitizing effect of exendin-4 (in contrast to the insulinotropic effect) does not involve the GLP-1 receptor pathway.     

The enhancement of sensory blockade by clonidine selectively added to mepivacaine after midhumeral block

Clonidine added to local anesthetics results in an increased duration of anesthesia or analgesia after brachial plexus block. We investigated the effect of selective application of clonidine to the median and musculocutaneous nerves during midhumeral block, a technique allowing selective nerve blocks with the use of different local anesthetics. Initially, 58 patients scheduled for hand surgery were prospectively enrolled to receive a midhumeral block. These patients were randomly allocated into two groups. The Control group (n = 28) received 10 mL of plain mepivacaine 1.5% for each nerve (median, musculocutaneous, ulnar, and radial). The Clonidine group (n = 30) received 10 mL of plain mepivacaine 1.5% for each nerve, but the median and musculocutaneous nerves also received a dose of 50 microg clonidine. One patient in the Control group and two patients in the Clonidine group with a failed block were therefore excluded from the analysis. The onset time of surgical anesthesia was recorded. The durations of sensory and motor blocks were checked every 15 min. The plasma mepivacaine concentration was analyzed from 10 patients in each group. Onset times for complete sensory block were similar between the two groups. Adding 50 microg clonidine to the median and musculocutaneous nerves resulted in a significant increase in the duration of sensory block in these nerves (P < 0.0001). Recovery of motor block was not different between the two groups. No significant difference was found between the two groups in the mean plasma mepivacaine concentration.     

Clinical and pathologic features of fibrillary glomerulonephritis.

A diagnosis of fibrillary glomerulonephritis was made in 31 renal biopsies from 28 patients on the basis of the electron microscopic identification of glomerular deposits of randomly arranged fibrils that resembled amyloidosis but were larger. This accounted for approximately 1% of all nontransplant renal biopsy diagnoses. Renal biopsy specimens with parallel arrays of 30 nm to 50 nm microtubules (that is, immunotactoid glomerulopathy) were not included in the study. The patients had a mean age of 49 years with a range of 21 to 75. The male to female ratio was 1:1.8 and the ratio of Whites to Blacks was 8.3:1, which differs from the 3:1 ratio in our overall biopsy population. All patients had proteinuria (mean 6.0 g/day), and most had hematuria and renal insufficiency. After a mean follow-up of 24 months, there was 48% renal survival. The light microscopic appearance of the fibrillary glomerulonephritis was quite varied. Capillary wall thickening and matrix expansion were the most frequent alterations. Nineteen percent of specimens had crescents. Morphometric ultrastructural analysis demonstrated a mean fibril diameter of 22.4 +/- 7.4 nm. Immunofluorescence microscopy revealed that IgG was the dominant and often the only immunoglobulin class in immune deposits, and subclass analysis revealed that IgG4 was the dominant or exclusive subclass in all specimens tested. We hypothesize that the relatively homogeneous nature of the immunoglobulin in the immune deposits is the basis for the fibril formation.     

Neuroblastoma in an adult

Neuroblastoma is extremely rare in adults. Advances in classification and therapy have been recently made by an analysis of pediatric tumors. We present the case of a 39-year-old man who had Stage 1 neuroblastoma with unfavorable histologic features that was treated with surgery only. Neuroblastoma should be considered as a diagnosis for adult patients with a suprarenal mass and, if confirmed, neuroblastoma in adults should be classified and treated according to pediatric guidelines.     

Successful percutaneous coil occlusion of a large pulmonary arteriovenous malformation

Pulmonary arteriovenous malformation is one of the rarest congenital anomalies of cardiovascular system. We present a case of 30-year-old female with a large pulmonary arteriovenous malformation (PAVM) arising from the right lower pulmonary artery and draining to the left atrium. She underwent successful embolization using three detachable Cook coils.