Liver cirrhosis due to chronic use of nitrofurantoin

A 74-year-old woman was admitted with jaundice. She was suffering from generalised liver failure with a highly prolonged prothrombin time, a low albumin level and ascites. Further anamnesis revealed that she had been taking nitrofurantoin as a prophylactic agent for recurrent urinary tract infections every day for 5 years. Because of the indications for liver damage due to nitrofurantoin, the drug was discontinued immediately on admission. After withdrawal of nitrofurantoin there was a very gradual clinical and biochemical improvement. Liver biopsies to confirm the diagnosis revealed extensive liver damage with cirrhosis such as may be seen following long-term use of nitrofurantoin. Nitrofurantoin should be prescribed with caution as a prophylactic agent in elderly women and patients with renal dysfunction because the risk of liver damage as a serious side effect of nitrofurantoin is greatly increased in these patients.     

Symptomatic epidural lipomatosis in ectopic Cushing's syndrome

We report a case of spinal epidural lipomatosis (SEL) caused by ectopic Cushing's syndrome and give a review of the literature. The most common cause of SEL is prolonged therapy with glucocorticoids, only a very few cases are related to endogenous Cushing's syndrome. The pathophysiological mechanism is not clear but there is a possible role for the autonomic nervous system in the stimulation of growth of epidural fat. Severe neurological symptoms which indicate myelopathy and radiculopathy can occur, but there is often a delay in diagnosis because the non-specific initial symptoms are not recognized. The epidural fat is mostly located in the thoracic and lumbar region. Magnetic resonance imaging can establish the diagnosis rapidly. In patients with severe neurological symptoms, surgical decompression of the myelum and removal of the epidural fat is the treatment of choice. Most patients have partial or complete recovery of neurological deficits after surgical treatment or after discontinuing glucocorticoid therapy; mild cases can also be treated conservatively. Routine imaging for the detection of epidural-located lipomatosis in patients at risk is probably useful.     

The epithelial sodium channel (ENaC) is intracellularly located as a tetramer

The epithelial sodium channel (ENaC) plays an important role in Na(+) homeostasis by determining the Na(+) transport rate in so-called end-organs such as the renal collecting duct, distal colon, salivary and sweat gland ducts. ENaC is formed by heteromultimerization of three homologous subunits, termed alpha, beta, and gamma ENaC. The number of subunits and stoichiometry remain a matter of debate. In this study, sucrose gradient analysis of Xenopus laevis oocytes expressing rENaC revealed that ENaC forms heterotetramers, when the membrane fraction was solubilized in 0.1% (wt/vol) Na-deoxycholate. However, solubilization of the membrane proteins in higher concentrations of detergents dissociated the ENaC subunits of the tetramers in dimers. Co-immunoprecipitation studies with FLAG-tagged ENaC subunits suggest that during dissociation of ENaC tetramers the composition of dimers is completely random. Glycosidase digestion studies show that the ENaC subunits are retarded in the endoplasmic reticulum (ER) and pre-Golgi, whereas only a small fraction is inserted into the plasma membrane. Immunocytochemical analysis confirmed that ENaC is primarily located intracellularly. In addition, these findings are not restricted to the oocyte expression system, since identical results were found in rabbit connecting tubule and cortical collecting duct cells in primary culture and in rabbit colon.     

Endotoxin impairs endothelium-dependent vasodilation more in the coronary and renal arteries than in other arteries of the rat

Endotoxemia may result in endothelial dysfunction, and some vascular beds may be affected more than others. To test this hypothesis, we studied, in vitro, the reactivity of isolated rat coronary, renal, superior mesenteric, and hepatic arteries exposed to endotoxin (E. coli, 50 microg. mL(-1)) or saline for 2 h at 37 degrees C. Vascular smooth muscle function was tested using 125 mM KCl, the vasoconstrictors norepinephrine (NE), and the thromboxane analog U46619 (coronary artery). Endothelium-dependent vasorelaxation was tested with acetylcholine (ACh) in preconstricted vessels. Although differing between vessel types, the smooth muscle contractile responses were not affected by endotoxin, either in the presence or absence of L-arginine. Endotoxin impaired the response to ACh in rat coronary arteries (92.7 +/- 4.6% vasodilation in control and 41.3 +/- 11.6% in endotoxin-exposed segments) and in renal arteries (66.7 +/- 5.2% vasodilation in control and 43.2 +/- 4.9% in endotoxin-exposed segments), so that there was a mean 55% decrease vs controls in coronary and a mean 35% decrease in renal arteries. Endotoxin did not affect superior mesenteric and hepatic arteries. Brief endotoxin exposure of isolated rat arteries may thus inactivate endothelial NO synthase, independent of iNOS. The increase in heterogeneity among endothelium-dependent vasodilation after endotoxin may help to explain early blood flow maldistribution in endotoxin shock.     

Shoshin beriberi provoked by the inhalation of salbutamol

A 45-year-old male alcoholic with a deficient diet was given salbutamol for exertion-related dyspnoea. After inhalation, he presented with a severe dyspnoea, acrocyanosis, anuria and low blood pressure as well as a respiratory compensated lactate acidosis. Shoshin beriberi was suspected on clinical grounds. The low level of thiamine and the prompt recovery after thiamine repletion confirmed this diagnosis. Shoshin beriberi is an acute, cardiac form of beriberi, which can rapidly result in death due to cardiogenic shock and lactate acidosis. Adrenergic agents can cause a hyperdynamic circulation and thus aggravate the effects of a thiamine deficiency.     

Diagnostic image (162) A woman with temporary hemiplegia. Temporary embolic occlusion of the left middle cerebral artery by a thrombus

A 48-year-old woman with right-sided hemiplegia by embolic occlusion of the left middle cerebral artery was treated with alteplase. A pre- and post-treatment CT angiography scan showed the vanishing blood clot.     

Early inhibition of activated fibrinolysis predicts microbial infection, shock and mortality in febrile medical patients

To evaluate the contribution of an imbalance between coagulation activation and fibinolysis activation and inhibition to morbidity and mortality in sepsis, we determined in medical hospitalized patients at inclusion (day 0) for fever (temperature above 38.0 degrees C axillary or 38.3 degrees C rectally), and daily thereafter for two days, circulating thrombin-antithrombin III (TAT) complexes, plasmin-alpha2-antiplasmin (PAP) complexes (day 0 only), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and interleukin (IL)-6, the latter as a marker of the inflammatory host response. Study variables were 1) positive microbiological results for specimens from local sites associated with a clinical infection, positive blood cultures (including parasitemia) or both, within 7 days after inclusion, 2) development of shock, i.e. systolic blood pressure <90 mmHg or a reduction of 40 mmHg from baseline within 7 days after inclusion, and 3) death related to febrile illness within 28 days after inclusion. The peak plasma levels of TAT complexes were elevated in 44% and the PAP complexes in all patients. The t-PA and PAI-1 levels were elevated in 74 and 94% of patients, respectively. Values for TAT and PAP did not differ among subgroups, while peak t-PA and IL-6 levels were higher in patients with positive microbiological results, developing shock or ultimately dying than in those without the complications (p<0.005). Peak PAI-1 levels were elevated in patients developing shock and ultimate death versus those with an uncomplicated course (p <0.05). Peak IL-6 related to PAI-1 and t-PA levels, which interrelated. Patients with elevated TAT levels had increased plasma levels of IL-6, PAP, PAI-1 and t-PA versus those with normal TAT (p <0.05). Our data indicate that inhibition of activated fibrinolysis, which may partly depend on both cytokinemia and activation of coagulation, predicts microbial infection, septic shock and mortality of febrile medical patients. This suggests an early pathogenic role of inhibition of activated fibrinolysis in the downhill course of serious microbial infection.