Patterns of healing of scaphoid fractures. The importance of vascularity

We studied 45 patients with 46 fractures of the scaphoid who presented sequentially over a period of 21 months. MRI enabled us to relate the pattern of the fracture to the blood supply of the scaphoid. Serial MRI studies of the four main patterns showed that each followed a constant sequence during healing and failure to progress normally predicted nonunion.     

Extradural endodermal cyst of posterior fossa: case report, review of the literature, and embryogenesis

OBJECTIVE AND IMPORTANCE: Posterior fossa endodermal cysts are rare. They are located in the midline, in ventral or ventrolateral locations, or intrinsic to the neural axis. Accordingly, various theories of embryogenesis have been proposed. We report the first case of an extradural, dorsolaterally situated endodermal cyst. CLINICAL PRESENTATION: An adult male patient presented with a short history of headache and cerebellar ataxia. Neuroimaging revealed an extra-axial cystic posterior fossa mass. INTERVENTION: An entirely extradural cyst was found and was totally excised. Immunohistochemistry confirmed the diagnosis of endodermal cyst. CONCLUSION: The extradural, dorsal location of the endodermal cyst suggests gaps at the cranial end of the notochord causing ectodermal-endodermal adhesions during early gastrulation and the persistence of endodermal remnants in the dorsal mesenchyme of the blastemal cranium. The literature is reviewed, and proposed theories of embryogenesis are discussed.     

Pharmacological studies on nitro‐naproxen (naproxen‐2‐nitrooxyethylester)

Naproxen‐2‐nitrooxyethylester (S‐(+)‐2‐(6‐methoxy‐2‐naphthyl)propanoic acid‐2‐nitrooxyethylester, LE‐EK06) was synthesized from naproxen and 2‐nitrooxyethylbromide as a novel nitric oxide–releasing derivative of naproxen. Molar equivalents of LE‐EK06 (6.93–27.73 mg/kg, p.o.) to naproxen dose‐dependently exhibited greater antinociceptive activity in comparison to naproxen in a writhing assay. The compound (5.54–22.18 mg/kg, p.o.) showed greater anti‐inflammatory activity at 2 h after as comparable to its effect at 4 h after carrageenan challenge in rats. Further, LE‐EK06 (9.45 mg/kg, p.o.) was more potent in the carrageenan‐evoked hyperalgesia. LE‐EK06 (11.09 mg/kg, p.o.) and naproxen (8.0 mg/kg, p.o.) showed a comparable inhibitory effect on exudate formation and migration of polymorphonuclear leukocytes (PMNs) in a carrageenan‐induced pleurisy test. Further, the compound (11.09 mg/kg, p.o.) significantly reduced myeloperoxidase activity in carrageenan‐treated paw and demonstrated significantly less gastrotoxicity in acute and chronic (21 days) studies. The scanning electron microscopy revealed that LE‐EK06 showed only mild gastric damage (slight disruption of mucus layer) in comparison to naproxen. The present study suggested that naproxen‐2‐nitrooxyethylester (LE‐EK06) represents a novel gastric sparing NSAID. Drug Dev. Res. 61:66–78, 2004. © 2004 Wiley‐Liss, Inc.     

Brief Clinical Report: Serum Tumor Necrosis Factor for Monitoring Response of Hepatic Veno-occlusive Disease to Pentoxiphyllin-A Case Report

Hepatic veno-occlusive disease (VOD) is the second most common cause of death after autologous bone marrow transplantation (ABMT). A patient with multiple myeloma undergoing ABMT developed classic features of hepatic VOD. He responded to treatment with pentoxiphyllin. Serum tumor necrosis factor (TNF) levels showed remarkable correlation with the severity of VOD and response to therapy.     

A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes

Type 2 diabetes is a polygenic disease characterized by defects in both insulin secretion and insulin action. We have previously reported that isolated insulin resistance in muscle by a tissue-specific insulin receptor knockout (MIRKO mouse) is not sufficient to alter glucose homeostasis, whereas beta-cell-specific insulin receptor knockout (betaIRKO) mice manifest severe progressive glucose intolerance due to loss of glucose-stimulated acute-phase insulin release. To explore the interaction between insulin resistance in muscle and altered insulin secretion, we created a double tissue-specific insulin receptor knockout in these tissues. Surprisingly, betaIRKO-MIRKO mice show an improvement rather than a deterioration of glucose tolerance when compared to betaIRKO mice. This is due to improved glucose-stimulated acute insulin release and redistribution of substrates with increased glucose uptake in adipose tissue and liver in vivo, without a significant decrease in muscle glucose uptake. Thus, insulin resistance in muscle leads to improved glucose-stimulated first-phase insulin secretion from beta-cells and shunting of substrates to nonmuscle tissues, collectively leading to improved glucose tolerance. These data suggest that muscle, either via changes in substrate availability or by acting as an endocrine tissue, communicates with and regulates insulin sensitivity in other tissues.     

High-affinity, calcium-stimulated ATPase in brush border membranes of the human term placenta

ATPase activity which is stimulated by submicromolar concentrations of calcium (Ca2+) was identified in human placental microvillous brush border membranes. The high-affinity enzyme has an apparent K0.5 for free Ca2+ of 18.3 +/- 3.7 nM and a Vmax of 233.0 +/- 30.0 nmol/min/mg protein. Studies using trans-1,2-diaminocyclohexane-N,N,N1,N1-tetraacetic acid (CDTA) show that this enzyme requires submicromolar concentrations of Mg2+ for maximal activity, but that it appears to have a low basal activity in the absence of this cation. The high-affinity Ca2+-ATPase was unaffected by up to 100 microM concentrations of vanadate, but was sensitive to trifluoperazine inhibition (I50 less than 50 microM). It was not found to be stimulated by the addition of up to 10 micrograms calmodulin, but this lack of effect may be related to the endogenous calmodulin content of the membrane preparation. A low-affinity, non-specific divalent cation ATPase was also identified in this membrane preparation. In contrast to the high-affinity enzyme, it has an apparent K0.5 for calcium of 99.7 +/- 22.1 microM, and a Vmax of 1.54 +/- 0.17 mumol/min/mg protein. The characteristics of the high-affinity Ca2-ATPase are similar to those of other Ca2+- ATPases known to transport and regulate intracellular calcium concentrations in other tissues. By analogy, we suggest that the high-affinity Ca2+-ATPase described here could play an important role in cellular calcium homeostasis in the human placenta.