Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety)

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.     

Acute hyperglycemia attenuates nerve conduction velocity and nerve blood flow in male Sprague–Dawley rats: reversal by adenosine

Hyperglycemia is implicated to play a major role in development of diabetic neuropathy. Since most of the diabetics are hyperglycemic much before they develop full-blown diabetes, we felt, it would be very important to know the effects of acute hyperglycemia on nerve function so that early pathophysiological events could be understood and appropriate therapeutic intervention can be made. Moreover, effect of acute hyperglycemia on motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) is not known. Hence, we studied the effects of acute hyperglycemia on sciatic MNCV and sciatic NBF in healthy male Sprague-Dawley (SD) rats. Three different animal models of acute hyperglycemia (50% glucose (3 g kg(-1), i.v. (intra-venous) or i.p. (intra-peritoneally)) or 24 h post-streptozotocin (STZ) injected rats were used. Acute hyperglycemia but not mannitol or sucrose significantly attenuated MNCV and NBF. Adenosine (10 mg kg(-1), i.p.) prevented the acute hyperglycemia-induced attenuation of MNCV and NBF in all the three rat models of acute hyperglycemia. Adenosine effects were blocked by theophylline (50 mg kg(-1), i.p.) suggesting the role of adenosinergic receptor mediated mechanisms in acute hyperglycemia-induced neuropathy. Acute glucose administration in 8 weeks, STZ diabetic rats did not further affect MNCV or NBF. Adenosine (10 mg kg(-1), i.p.) did not produce any adverse effects on the blood pressure and heart rate. From the results, we conclude that acute hyperglycemia attenuates MNCV and NBF via an adenosinergic receptor-dependent mechanism.     

Thorotrast-induced cholangiocarcinoma: case report

Thorotrast, a contrast medium used extensively before being banned in 1950s, delivers a densely ionizing, high linear energy transfer type of radiation that predisposes to malignancies. We report a case of peripheral cholangiocarcinoma and describe its computed tomographic and magnetic resonance imaging features in a patient who developed it 48 years after exposure to Thorotrast.     

Functional analysis of CaIPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans

In the present study we describe the isolation and functional analysis of a sphingolipid biosynthetic gene, IPT1, of Candida albicans. The functional consequence of the disruption of both alleles of IPT1 was confirmed by mass analysis of its sphingolipid composition. The disruption of both alleles or a single allele of IPT1 did not lead to any change in growth phenotype or total sphingolipid, ergosterol, or phospholipid content of the mutant cells. The loss of mannosyl diinositol diphosphoceramide [M(IP)(2)C] in the ipt1 disruptant, however, resulted in increased sensitivity to drugs like 4-nitroquinoline oxide, terbinafine, o-phenanthroline, fluconazole, itraconazole, and ketoconazole. The increase in drug susceptibilities of ipt1 cells was linked to an altered sphingolipid composition, which appeared to be due to the impaired functionality of Cdr1p, a major drug efflux pump of C. albicans that belongs to the ATP binding cassette superfamily. Our confocal and Western blotting results demonstrated that surface localization of green fluorescent protein-tagged Cdr1p was affected in ipt1 disruptant cells. Poor surface localization of Cdr1p resulted in an impaired ability to efflux fluconazole and rhodamine 6G. The effect of mannosyl inositol phosphoceramide accumulation in the ipt1 mutant and the absence of M(IP)(2)C from the ipt1 mutant on the efflux of drug substrates was very selective. The efflux of methotrexate, a specific substrate of CaMdr1p, another major efflux pump of major facilitator superfamily, remained unaffected in ipt1 mutant cells. Interestingly, changes in sphingolipid composition affected the ability of mutant cells to form proper hyphae in various media. Taken together, our results demonstrate that an altered composition of sphingolipid, which is among the major constituents of membrane rafts, affects the drug susceptibilities and morphogenesis of C. albicans.     

Scrotal involvement in Madelung disease: clinical, ultrasound and MR findings

Multiple symmetrical lipomatosis, also known as Madelung disease, Launois-Bensaude syndrome, and benign symmetrical lipomatosis, is an uncommon disease that is characterized by the presence of multiple and symmetrical deposits of nonencapsulated adipose tissue in the neck, upper trunk, arms, and legs. It affects mainly men, with a higher incidence in the Mediterranean area, and is typically associated with high alcohol consumption and a high prevalence of peripheral neuropathy that usually appears long after the development of lipomatous masses. We report the case of a patient with involvement of the scrotum. We present clinical, ultrasound, and magnetic resonance appearances of these scrotal lipomatous masses for the first time.     

Orthopaedic surgeon＇s nightmare： iatrogenic fractures of talus and medial malleolus following tibial nailing

Intramedullary interlocking nailing is the gold standard for treatment of tibial shaft fractures.The growing use of intramedullary nailing has resulted in an increased number of tibial nailing in daily...     

Danger of helmet continuous positive airway pressure during failure of fresh gas source supply

Objective To assess the behavior of different helmets after discontinuation of fresh gas flow by disconnection at the helmet inlet, flow generator, or gas source. Design and setting Randomized physiological study in a university research laboratory. Patients Five healthy volunteers. Intervention CPAP (FIO₂ 50%, PEEP 5 cmH₂O) delivered in random sequence with three different helmets: 4Vent (Rüsch), PN500 (Harol), CaStar (StarMed) with antisuffocation valve open or locked. For each helmet all three disconnections were randomly employed up to 4 min. Measurements and results During flow disconnection we measured: respiratory rate and tidal volume by respitrace; inspiratory and expiratory CO₂ concentration, and FIO₂ from a nostril; SpO₂ by pulse oxymetry. Independently of the site of disconnection we observed a fast increase in CO₂ rebreathing and minute ventilation, associated with a decrease in inspired O₂ concentration. In the absence of an operational safety valve, larger helmet size and lower resistance of the inlet hose resulted in slower increase in CO₂ rebreathing. The presence of the safety valve limited the rebreathing of CO₂, and the increase in minute ventilation but did not protect from a decrease in FIO₂ and loss of PEEP. Conclusions While the use of a safety valve proved effective in limiting CO₂ rebreathing, it did not protect from the risk of hypoxia related to decrease in FIO₂ and loss of PEEP. In addition to a safety antisuffocation valve, a dedicated monitoring and alarming systems are needed to employ helmet CPAP safely.