Idiopathic thrombocytopenic purpura in a liver transplant recipient with previous primary biliary cirrhosis

The loss of immunotolerance has been implicated in the pathogenesis of both primary biliary cirrhosis (PBC) and idiopathic, immune-mediated thrombocytopenic purpura (ITP). An association between these two autoimmune diseases has been well described. We describe a 41-year-old woman in whom ITP developed 457 days after liver transplantation for PBC while receiving immunosuppressive medications sufficient to maintain allograft function. Our case report, the first to describe post-transplant ITP in association with PBC, demonstrates the persistence of the underlying immune dysregulation of PBC after transplantation. The practice of decreasing the dosage of immunosuppressive medication to maintenance levels after transplantation may unmask the effects of this defect in immunotolerance.     

Incisional hernia after laparoscopic nephrectomy with intact specimen removal: caveat emptor

The choline-containing phosphoglycolipid, MfGL-II, is the major polar lipid of Mycoplasma fermentans PG18. Anti-MfGL-II antisera raised in rabbits using the purified MfGL-II as an immunogen were employed in immunogold electron microscopic and immunofluorescence studies showing that MfGL-II is uniformly distributed and exposed on the cell surface of M. fermentans cells. The specificity of the antibodies was determined by immunostaining of lipid extracts separated by thin layer chromatography. The antibodies recognize lipids specific to M. fermentans but did not cross-react with lipid extracts of M. penetrans, M. capricolum, M. gallisepticum or Acholeplasma laidlawii. As phosphocholine almost completely abolished antibody interaction with MfGL-II in an ELISA assay it is suggested that the anti-MfGL-II repertoire is composed primarily of anti-phosphocholine antibodies. The anti-MfGL-II antisera inhibit the attachment of M. fermentans to Molt-3 lymphocytes suggesting that MfGL-II plays a major role in M. fermentans-host cell interaction.     

Benign intracranial hypertension in children

Ceftriaxone has a very high plasma protein binding (up to 98%) that is saturable and decreases with higher concentrations. This high protein binding results in high concentrations in plasma that are frequently related to the anti-infective activity. However, because only the free fraction of the drug is pharmacologically active and most of the infections are located in the tissues, it is more relevant to evaluate unbound concentrations in the interstitial space. Plasma and tissue pharmacokinetics of ceftriaxone in rats after single intravenous administration were investigated at two different concentrations (50 and 100 mg/kg). Both plasma and tissue samples were taken simultaneously from the same animal and analyzed by reversed-phase high-performance liquid chromatography. Free tissue levels in the thigh muscle were measured by microdialysis. The concentration in plasma is much higher than the free concentration in tissue. After determination of nonlinear protein binding by microdialysis and including these parameters in the pharmacokinetic model, it is possible to predict free concentrations in the interstitial space from plasma levels for any given dose.     

Effect of calcium and fat intake on calcium metabolism in calves

Ten male Holstein calves were fed diets with or without 5% added animal fat in combination with low and high dietary calcium (.15 or .98%) for 4 wk. After 3 wk, the animals were orally dosed with calcium-45. One week later they were killed and tissue samples taken. Except for lower calcium-45 in bile, added dietary fat had no marked influence on calcium metabolism. Net absorption of calcium-45 (not excreted in feces) ranged from 82% for calves fed low calcium to 53% for those given high calcium. Calcium-45 in bone was substantially higher in calves fed .15% calcium. Tailbone biopsies revealed rapid uptake of calcium-45 with approximately as much incorporated during the 1st d as in the following 6 d. Calcium-45 in blood peaked 24 h following dosing. Calves fed .15% calcium had higher calcium-45 in blood and bile than those receiving .98% calcium. Calcium-45 values in soft tissue were low and did not differ materially among treatments. The decreases in radioactive calcium absorption and bone deposition with higher dietary calcium indicated that variable absorption was a major factor in calcium homeostasis. Added fat did not materially effect calcium metabolism with either low or high dietary calcium.     

Firm Partial Modularity and Performance in the Electronic Manufacturing Services Industry

Firms continue to develop new ways to decentralize non-core activities to outside parties. Scholars have approached this issue with modularity theory, suggesting a continuum of arrangements ranging from hierarchy to market. Hierarchy relies on fiat, while partially modular forms, those forms between hierarchy and market, require greater coordination, communication and relationships between firms than do fully modular (or market) forms. While modularity theory identifies this continuum, the associated empirical literature tends to dichotomize modularity: firms are either modular or they are not. Nor does the empirical literature examine the performance outcomes of modular arrangements within this continuum. By examining firms that vary between full integration and partial modularity with a continuous modularity measure, this paper empirically examines the performance outcomes associated with a range of modularity levels. We derive this measure from a peculiar inventory option available within the electronic manufacturing services (EMS) industry. Our data include observations on 260 firms over five years. We find that more firms rely on partially modular arrangements, the lower their performance. We suggest explanations for this result, and areas of future research meant to pursue it.     

Structurally related peptide agonist, partial agonist, and antagonist occupy a similar binding pocket within the cholecystokinin receptor. Rapid analysis using fluorescent photoaffinity labeling probes and capillary electrophoresis

The molecular basis of ligand binding to receptors provides important insights for drug development. Here, we explore domains of the cholecystokinin (CCK) receptor that are critical for ligand binding, using a novel series of fluorescent photolabile probes, receptor proteolysis, and rapid high resolution separation of peptide fragments by capillary electrophoresis. Each probe incorporated the same fluorophore and a photolabile p-benzoylphenylalanine at the amino terminus of the pharmacophoric domain (residue 24 of CCK-33) of CCK analogues representing full agonist, partial agonist, and antagonist of this receptor. Each was used to label the CCK receptor expressed on Chinese hamster ovary-CCKR cells, with the labeled domain then released by cyanogen bromide cleavage. Capillary electrophoresis with laser-induced fluorescence detection achieved an on-capillary mass sensitivity of 1.6 attomoles (10(-18) mol), with an excellent signal-to-noise ratio. Each of the biologically divergent, but structurally similar probes saturably and specifically labeled the same receptor domain, consistent with conservation of "docking" determinants. This had an apparent mass of 2.9 kDa, most consistent with the first extracellular loop domain. An additional probe having its site of covalent attachment in a different region of the probe (residue 29 of CCK-33) labeled a distinct receptor fragment with differential migration on capillary electrophoresis (third extracellular loop). Identification of the specific receptor residue(s) covalently linked to the amino-terminal probes must await further fragmentation and sequence analysis.     

The relationship of chronic mucin secretion to airway disease in normal and CFTR-deficient mice

In the cystic fibrosis (CF) patient, lung function decreases throughout life as a result of continuous cycles of infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus. The mechanism underlying the pathophysiology of the disease in humans has not been established. However, it has been suggested that abnormal, tenacious mucus, resulting perhaps from improper hydration from loss of Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) protein, impairs clearance of bacteria from the CF airway and provides an environment favorable to bacterial growth. If this hypothesis is correct, it could explain the absence of respiratory disease in CFTR-deficient mice, since mice have only a single submucosal gland and display few goblet cells in their lower airways, even when exposed to bacteria. To test this hypothesis further, we induced allergic airway disease in CFTR-deficient mice. We found that induction of allergic airway disease in mice, unlike bacterial infection, results in an inflammatory response characterized by goblet cell hyperplasia, increased mucin gene expression, and increased production of mucus. However, we also found that disease progression and resolution is identical in Cftr-/- mice and control animals. Furthermore, we show that the presence of mucus in the Cftr-/- airway does not lead to chronic airway disease, even upon direct inoculation with S. aureus and P. aeruginosa. Therefore, factors in addition to the absence of high levels of mucus secretion protect the mouse from the airway disease seen in human CF patients.     

Refusal to eat in the elderly

Refusal to eat by the elderly, and subsequent malnutrition, occurs in both institutional and community settings. Causes include physiologic changes associated with aging, mental disorders such as dementia and depression, and medical, social, and environmental factors. Treatment approaches call for management of these causes while considering the roles that medicine, ethics, and culture play in the process.