Innervation of the proximal human biliary tree.

The autonomic nervous system plays a role in a variety of liver regenerative and metabolic functions, including modulating bile secretion and cholangiocyte and hepatobiliary progenitors of the canals of Hering. However, the nature and location of nerves which link to the proximal biliary tree have remained uncertain. We investigate the anatomic relationship of nerves to the proximal biliary tree including the putative stem/progenitor cell niche of the canal of Hering. Using double immunostaining (fluorescence, histochemistry) to highlight markers of cholangiocytes (biliary-type keratins), nerves (S100, neurofilament protein, PGP9.5, tyrosine hydroxylase), and stellate cells (CRBP-1), we examined sections from normal adult livers from autopsy or surgical resections. There is extensive contact between nerves and interlobular bile ducts, bile ductules, and canals of Hering (CoH). In multiple serial sections from 4 normal livers, biliary-nerve contacts were seen in all of these structures and were more common in the interlobular bile ducts (78/137; 57%) than in the ductules and CoH (95/294; 33%) (p < 0.001). Contacts appear to consist of nerves in juxtaposition to the biliary basement membrane, though crossing through basement membrane to interface directly with cholangiocytes is also present. These nerves are positive for tyrosine hydroxylase and are, thus, predominately adrenergic. Electron microscopy confirms nerves closely approximating ductules. Nerve fiber-hepatic stellate cell juxtaposition is observed but without stellate cell approximation to cholangiocytes. We present novel findings of biliary innervation, perhaps mediated in part, by direct cholangiocyte-nerve interactions. The implications of these findings are protean for studies of neuromodulation of biliary physiology and hepatic stem/progenitor cells.

Role of sodium thiosulfate therapy in the treatment of digital necrosis due to Mönckeberg sclerosis.

Accelerated vascular calcification is a well-described complication of chronic kidney disease often affecting large and small vessels alike through a variety of mechanisms. Accordingly, dysregulation of calcium and phosphate balance, vitamin D metabolism, hyperparathyroidism, and endothelial injury can lead to both macrovascular and microvascular complications. We describe a 56-year-old Hispanic male with a history of end-stage renal disease, diabetes mellitus type 2, and medical noncompliance who developed sequential digital ischemia and necrosis involving both hands as well as right foot as a result of Mönckeberg sclerosis. An extensive metabolic and serologic workup was unrevealing but radiographic studies and histopathology revealed the diagnosis. A multifaceted approach was instituted including wound debridement and amputations along with intensive medical support. In addition to improving hypertensive control and striving for improved calcium and phosphate balance, sodium thiosulfate solution was administered for more than 1 year. This aggressive approach allowed his wounds to heal and has arrested further digital ischemia from occurring.

Cryptococcal osteomyelitis of the humeral head initially diagnosed as avascular necrosis.

Cryptococcal skeletal infections can lead to significant morbidity and mortality and should be considered in the differential diagnosis of lytic osseous lesions. Clinical and radiological similarities to various disorders may lead to delay in initiation of antifungal treatment. This report describes a case of cryptococcal osteomyelitis of humeral bone in a 19-year-old female, emphasizing the clinical presentation, diagnostic approach and treatment options.