Theophylline toxicity secondary to ciprofloxacin administration

We report the case of a 79-year-old woman who presented from a skilled nursing facility to the emergency department with signs and symptoms of theophylline toxicity and a serum theophylline concentration of 53.7 mg/L. The patient had been on a regular regimen of aminophylline for two months, with the addition of ciprofloxacin three days before arrival as the only identifiable potential cause of theophylline intoxication. She was monitored and treated conservatively with serial doses of activated charcoal, which resulted in a reduction of her serum theophylline level to a therapeutic concentration in 15 hours without adverse sequelae. The number of cases of theophylline intoxication secondary to concurrent ciprofloxacin administration is likely to increase, especially in nursing home populations, and it should be suspected when these patients present to the ED with the appropriate signs and symptoms. Management of theophylline intoxication should be based on clinical presentation as well as concentrations of the drug.     

Platelet membrane glycoprotein changes during the preparation and storage of platelet concentrates

Previous studies of platelet membrane glycoproteins during blood bank storage have reported conflicting results. This study assessed two major plasma membrane glycoproteins (GP Ib and GP IIb), an alpha-granule membrane protein (GMP-140), and the concentration of platelet membrane microparticles in cell-free plasma during routine hospital blood bank platelet storage. 125I-monoclonal antibody binding was used to measure membrane glycoproteins on the surface of intact platelets and to measure the concentration of membrane microparticles in cell-free plasma. Platelet concentrates were stored at room temperature in polyolefin bags for 7 days. In this blood bank, two types of rotators are routinely used for platelet concentrate storage: a 2-rpm circular tumbler rotator and a 6-rpm elliptical rotator. Different results were obtained with the rotators. With the tumbler rotator, there was no loss of platelets and antibody binding to GP Ib remained normal. With the elliptical rotator, one third of platelets were lost into clumps during storage, and a 50 percent decrease of antibody binding to GP Ib occurred in the remaining single platelets. There was no loss of antibody binding to GP IIb with either rotator. Antibody binding to GMP-140 increased equally in both rotators indicating that the remaining single platelets had secreted about 16 percent of their alpha-granule contents. The plasma concentration of platelet membrane microparticles was greater in the bags stored in the elliptical rotator. These results indicate that it is possible to maintain the normal concentration of platelet membrane glycoproteins Ib and IIb during 7 days of room-temperature blood bank storage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet-collagen interaction: inhibition by ristocetin and enhancement by von Willebrand factor-platelet binding

The contribution of von Willebrand factor (vWF)-platelet binding to platelet-collagen interaction was examined in vitro. The binding of vWF to platelets was mediated and regulated by ristocetin. Subthreshold concentrations of ristocetin (less than or equal to 1 mg/mL), insufficient to cause ristocetin-induced platelet aggregation (RIPA), were added to platelet-rich plasma (PRP) prior to the addition of collagen. The collagen-induced platelet aggregation (CIPA) was modified by ristocetin and the degree of alteration was dependent on the ristocetin concentration. Response as a function of ristocetin concentration was designated the Collagen-Platelet Aggregation Response (CoI-PAR). In normal PRP the CoI-PAR was a progressive inhibition followed by decreasing inhibition and then an enhanced response. The enhanced response occurred over a narrow range of ristocetin concentrations (0.8 to 1.0 mg/mL). In the absence of vWF (severe von Willebrand's disease, Type I, vWF less than 1%) the CoI-PAR was a progressive, eventually complete inhibition with no enhanced response (with ristocetin concentrations up to 3.0 mg/mL). With addition of vWF to this PRP an enhanced response was observed at a ristocetin concentration inversely proportional to the vWF level. PRP from a patient with severe Hemophilia A showed a response within the normal range. Subthreshold ristocetin did not cause plasma protein precipitation or platelet release of 3H-serotonin, nor induce micro platelet aggregate formation. Digestion of platelet membrane glycoproteins (GP(s] with chymotrypsin demonstrated that upon removal of GPI, RIPA was absent, CIPA retained and the CoI-PAR was progressive inhibition, with no enhancement. With removal of GPs I, II, and III, RIPA, CIPA, and the CoI-PAR were absent. A dose-response 125I-vWF- platelet binding occurred with increasing ristocetin concentrations which was unchanged by the addition of collagen. These results demonstrated that ristocetin-platelet association inhibited CIPA, and vWF-platelet binding enhanced platelet-collagen adhesion and platelet aggregation. The in vitro-enhanced CIPA represents a vWF-dependent aggregation of sufficient magnitude to overcome the inhibitory effect of ristocetin. These studies demonstrate an influential interaction of ristocetin, vWF, and collagen with the platelet membrane and imply an important hemostatic contribution of vWF-platelet binding in platelet- collagen interaction.     

Esophageal motor function in patients with muscular dystrophy

In a study designed to evaluate esophageal motor function in muscular dystrophy we examined 13 patients with myotonic dystrophy, 14 patients with "nonmyotonic" muscular dystrophy, and 8 healthy control subjects by manometric and radionuclide transit studies. Patients with myotonic dystrophy exhibited a marked weakness of esophageal contractions and upper esophageal sphincter pressure. Coordination of sphincter relaxation and peristaltic sequences remained unaltered. These changes led to delayed esophageal emptying in all patients with myotonic dystrophy. Although esophageal function was also impaired in the distal esophagus, on histologic studies, morphologic alterations were confined to esophageal striated muscle in a single patient with myotonic dystrophy. In contrast to the marked dysfunction of esophageal motility in patients with myotonia, no such alterations were observed in the "nonmyotonic" form of muscular dystrophy.     

Surfactant abnormalities in idiopathic pulmonary fibrosis, hypersensitivity pneumonitis and sarcoidosis.

Bronchoalveolar lavage fluids (BALF) from patients with idiopathic pulmonary fibrosis (IPF; n=36), hypersensitivity pneumonitis (HP; n=32) and sarcoidosis (n=44) were investigated for their surfactant properties and compared to healthy control subjects (n=29). The phospholipid (PL) and protein concentration, the PL:protein ratio, PL subclasses, and the surfactant apoproteins (SP)A and SP-B were quantified in BALF. Large surfactant aggregates (LSA) were measured by means of ultracentrifugation and assayed for surface activity using the pulsating bubble surfactometer. As compared to controls, SP-A concentrations, LSA content and PL:protein ratios were significantly decreased in all groups, whereas PL and SP-B concentrations remained unchanged. Changes in the phospholipid profile, with reduced percentages of phosphatidylcholine (not significant) and phosphatidylglycerol and increased fractions of phosphatidylinositol and sphingomyelin (p<0.05), occurred more in IPF than in HP, and not in sarcoidosis. Surface activity was found to be severely impaired in IPF (minimum surface tension (gamma min) approximately 15-20 mN x m(-1)), but only modestly affected in HP and sarcoidosis (gamma min approximately 5 mN x m(-1)) compared to controls (gamma min approximately 0 mN x m(-1)). Reconstitution of pelleted surfactant material with soluble BALF proteins further increased gamma min values. In conclusion, moderate changes in biochemical and physical surfactant properties are encountered in hypersensitivity pneumonitis and sarcoidosis, but pronounced disturbances occur in idiopathic pulmonary fibrosis.     

Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice

Ceramide generated by lysosomal acid sphingomyelinase (aSMase) has been proposed to contribute to CD28 co-stimulatory signaling pathways. We used an aSMase-deficient mouse line ( asmase ^{− / −} ) to elucidate the role of the aSMase in splenocytes stimulated with either a combination of anti-CD3 and anti-CD28 antibodies, the lectin concanavalin A (Con A) or the superantigen staphylococcal enterotoxin B. All stimuli were shown to induce IL-2 expression, Con A additionally triggered the expression of high-affinity IL-2 receptor. However, in asmase ^{− / −} mice secretion of IL-2 was significantly reduced, whereas the intracellular IL-2 levels were elevated. Proliferation of anti-CD3/anti-CD28 or Con A-stimulated aSMase-deficient splenocytes was reduced up to 50 % after 72 h in comparison to wild-type cells. We conclude that ceramide generated by aSMase is not involved in CD28 signal transduction, but rather a perturbation of the secretory system is responsible for the impaired proliferation of aSMase-deficient splenocytes.     

Time to positive culture and identification for Candida blood stream infections

Candidemia and delay to appropriate therapy contribute to increased morbidity and mortality. Current literature addresses the delay between blood culture collection and final identification; however, it fails to delineate differences among species. The purpose of this study was to quantify the time to yeast detection and identification relative to blood culture collection and determine whether differences exist among species. In this retrospective study, all cases of Candida isolation for 2 years were reviewed. The time delays between blood culture and detection of Candida growth were quantified as well as the additional time required for final species identification. Initiation of antifungal therapy was assessed in relation to culture collection, detection of yeast, and final identification. The appropriateness of therapy at each time point was also analyzed. Most Candida infections were caused by either Candida albicans (n = 43) or Candida glabrata (n = 27). Mean time to positive yeast detection for C. albicans was 35.3 ± 18.1 h, whereas that of C. glabrata was 80.0 ± 22.4 h (P < 0.0001). Mean time to final identification for C. albicans was 85.8 ± 30.9, whereas that of C. glabrata was 154 ± 43.8 h (P < 0.0001). Mean time to appropriate therapy for C. albicans isolates was 43.3 ± 27.6 h compared with 98.1 ± 38.3 h (P < 0.0001) for C. glabrata isolates. The time delay between blood culture collection and yeast detection as well as final identification was significantly longer for C. glabrata isolates when compared with C. albicans. As a result, mean time to appropriate antifungal therapy was significantly longer in patients with C. glabrata isolates.