Disruption of the purine nucleotide cycle by inhibition of adenylosuccinate lyase produces skeletal muscle dysfunction.

Controversy exists as to whether the purine nucleotide cycle is important in normal skeletal muscle function. Patients with disruption of the cycle from a deficiency of AMP deaminase exhibit variable degrees of muscle dysfunction. An animal model was used to examine the effect of inhibition of the purine nucleotide cycle on muscle function. When the compound 5-amino-4-imidazolecarboxamide riboside (AICAriboside) is phosphorylated to the riboside monophosphate in the myocyte it is an inhibitor of adenylosuccinate lyase, one of the enzymes of the purine nucleotide cycle. AICAriboside was infused in 28 mice, and 22 mice received saline. Gastrocnemius muscle function was assessed in situ by recording isometric tension developed during stimulation. The purine nucleotide content of the muscle was measured before and after stimulation. Disruption of the purine nucleotide cycle during muscle stimulation was evidenced by a greater accumulation of adenylosuccinate, the substrate for adenylosuccinate lyase, in the animals receiving AICAriboside (0.60 +/- 0.10 vs. 0.05 +/- 0.01 nmol/mumol total creatine, P less than 0.0001). There was also a larger accumulation of inosine monophosphate in the AICAriboside vs. saline-treated animals at end stimulation (73 +/- 6 vs. 56 +/- 5 nmol/mumol total creatine, P less than 0.03). Inhibition of flux through the cycle was accompanied by muscle dysfunction during stimulation. Total developed tension in the AICAriboside group was 40% less than in the saline group (3,023 +/- 1,170 vs. 5,090 +/- 450 g . s, P less than 0.002). An index of energy production can be obtained by comparing the change in total phosphagen content per unit of developed tension in the two groups. This index indicates that less high energy phosphate compounds were generated in the AICAriboside group, suggesting that interruption of the purine nucleotide cycle interfered with energy production in the muscle. We conclude from these studies that defective energy generation is one mechanism whereby disruption of the purine nucleotide cycle produces muscle dysfunction.

Vertex epidural hematomas: imaging findings and diagnostic pitfalls.

PURPOSE: Our purpose was to show the computed tomography (CT) and magnetic resonance (MR) imaging features of vertex epidural hematomas (EDHs) and emphasize pitfalls in the diagnosis of this entity. SUBJECTS AND METHODS: The neuroradiologic studies of four patients (CT in four, MR imaging and MR venography in one) were evaluated for EDH shape, size and appearance. RESULTS: EDHs were biconvex in three patients and crescentic in one patient. CT appearances included a collection that was hyperdense (two patients), generally isodense with a few regions of hyperdensity (one patient) and mixed hyperdense and hypodense (one patient). MR imaging findings in one patient consisted of hyperintense signal on T1-weighted images and hypointense signal on T2-weighted images. Inferior displacement of the superior sagittal sinus was seen in two patients. Diagnosis of a small vertex EDH was difficult on routine axial CT in one patient, but apparent on MR imaging and MR venography. CONCLUSIONS: Small vertex EDHs can be difficult to diagnose on routine CT. MR imaging or thin section CT should be performed to exclude the diagnosis in patients with trauma to the skull vertex.

Fat-filled postoperative renal cortical defects: sonographic and CT appearance.

Surgical filling of renal cortical wedge resection defects with vascularized retroperitoneal fat resulted in postoperative sonographic and CT appearances that simulated focal renal masses in four patients. Correct identification of this abnormality is important in order to avoid unnecessary further evaluation to exclude renal neoplasm.

Comparison of [125I]HIPDm and [125I]iodoantipyrine in quantifying regional cerebral blood flow in rats.

We determined regional cerebral blood flow (rCBF) using [125I]HIPDm [N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamin e] and [125I]iodoantipyrine autoradiography under control and pathologic conditions (hypercapnia [acidosis], hypocapnia [alkalosis], and disrupted blood-brain barrier) conditions in 35 rats. In control rats, HIPDm rCBF (indicator fractionation method, n = 5) was lower than the corresponding IAP rCBF (diffusible indicator method, n = 4), most notably in the infratentorial regions and subcortical nuclei. In hypercapnia, rCBF increased by 100% and 37% in the HIPDm (n = 5) and IAP (n = 5) groups, respectively. In hypocapnia, IAP rCBF (n = 4) decreased 34% but HIPDm rCBF (n = 4) did not change. Following disruption of the blood-brain barrier by intracarotid infusion of mannitol in eight rats, both radiotracers (HIPDm n = 4, IAP n = 4) showed decreased rCBF to regions of disruption as defined by trypan blue extravasation. Our work indicates that modeling HIPDm uptake to quantify rCBF using the indicator fractionation method will underestimate blood flow and that HIPDm kinetics are influenced by compartmental pH dynamics that will limit the accuracy of this method in quantifying rCBF in pathologic conditions.