Successful algorithm for selective liver biopsy in the right hepatic lobe live donor (RHLD).

Routine versus selective predonation liver biopsy (LBx) remains controversial for assuring the safety of right hepatic lobe live donor (RHLD). Between December 1999 and March 2007, 403 potential RHLD were evaluated; 142 donated. Indications for selective LBx were: abnormal liver function tests or imaging studies, body mass index (BMI) >28, history of substance abuse or family history of immune mediated liver disease. All donors had a LBx at the time of surgery. Of 403 potential RLD, 149(36.9%) were accepted as donors, 25(6.3%) had their recipient receive a deceased donor graft, 94(23.4%) were rejected, 52(12.9%) stopped the evaluation process, 76(18.8%) withdrew from the process and 7(1.7%) are currently completing evaluation. Eighty-seven (21.5%) met criteria and were biopsied. Seventy-three (83.9%) had either normal (n = 24) or macrosteatosis <10% (n = 49); 51 of these donated. Abnormal LBx eliminated 15 potential donors. No significant abnormalities were found in donation biopsies of donors not meeting algorithm criteria. Three of 87 (3.4%) had complications requiring overnight admission (2 for pain, 1 for bleeding; transfusion not required). Use of this algorithm resulted in 78% of potential donors avoiding biopsy and potential complications. No significant liver pathology was identified in donors not meeting criteria for evaluation LBx. Routine predonation LBx is unnecessary in potential RHLD.

Biochemistry of type IV secretion.

In the past year, our knowledge of type IV transporters of Gram-negative bacteria has further expanded. Advances include the discovery of additional members of this family of proteins, increased knowledge of the morphologies of type IV transporters, and a better understanding of the mechanisms by which macromolecules are exported by these systems.

Adaptation of a conjugal transfer system for the export of pathogenic macromolecules.

Conjugal transfer of bacterial plasmids requires a pore through which DNA can traverse the envelopes of the donor and recipient cells. Recent studies indicate that these pores, which are composed of approximately ten proteins, are evolutionarily related to the transport systems required for the transfer of oncogenic T-DNA from Agrobacterium tumefaciens to plant cells and for toxin secretion from Bordetella pertussis.

Toxicity of parenteral iron dextran therapy.

Parenteral iron dextran is efficacious and safe for iron repletion in patients with iron-deficiency anemia. The risk for developing reactions to parenteral iron infusion can be attenuated if patients are carefully selected. Patients with underlying autoimmune disease, malnutrition with indolent infection, and risk for iron overload syndromes should be carefully monitored for complications. Further, the rate of infusion and the route of administration of iron dextran play roles in the risk of adverse reactions. The purpose of this review is to identify and elucidate the mechanisms of the acute and chronic toxicities associated with parenteral iron dextran use.

Live donor adult liver transplantation using right lobe grafts: donor evaluation and surgical outcome.

HYPOTHESIS: Live donor adult liver transplantation (LDALT) is a safe and efficacious treatment for patients with end-stage liver disease. DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit. PATIENTS: From December 10, 1998, through April 10, 2000, a single team performed 15 LDALT procedures with 2 simultaneous living donor kidney transplants. During this period, 66 potential donors were screened and evaluated. INTERVENTIONS: Potential donors were evaluated with 3-dimensional helical computed tomographic scan, including volume renderings for hepatic lobar volume, vascular anatomy, virtual resection planes, and morphologic features. Suitable donors undergo complete medical and psychiatric evaluation and preoperative arteriography. MAIN OUTCOME MEASURES: Donor demographics, evaluation data, operative data, hospital length of stay, and morbidity. RESULTS: A total of 38 men (58%) and 28 women (42%) were evaluated with 15 donors participating in LDALT. Two additional donors provided kidney grafts for simultaneous transplantation at the time of LDALT. Thirty-two donors (48%) were rejected for either donor or recipient reasons, and 10 patients (15%) elected not to participate after initial screening. Three-dimensional volume renderings by helical computed tomographic scan predicted right lobe liver volume within 92% of actual graft volume. Donor morbidity, including all complications, was 67% with no mortality. Residual liver regenerated to approximately 70% of initial volume within 1 week and 80% within 1 month after surgery. CONCLUSIONS: Donor evaluation is an important component of LDALT. Significant donor morbidity is encountered even with careful selection. To minimize donor morbidity, groups considering initiating living donor programs should have expertise in hepatic resection and vena cava preservation using the "piggyback" technique during liver transplantation.

Bordetella heat-labile toxin causes release of radioactivity from smooth muscle cells labeled with [14C]arachidonic acid.

The effect of Bordetella heat-labile toxin (HLT) on cultured vascular or tracheal smooth cells labeled with [14C]arachidonic acid for 3 h was examined. At 37 degrees C, in the presence of Ca2+, HLT induced the release of radioactive substances from the cells in a dose-dependent manner but HLT had no effect on release of radioactivity from cells at 0 degrees C or in the absence of Ca2+. After cells were exposed to HLT, a 2-h lag period occurred before release of radioactivity was detected. The substances released from cells by HLT were identified as arachidonic acid and phosphatidylcholine.

Purification and analysis of the antigenicity of a 69,000 Da protein from Bordetella pertussis.

A purification scheme was devised for a 69-kDa outer membrane protein of Bordetella pertussis, a virulence-associated protein which may play a role in the pathogenesis of the organism. The protein was purified to apparent homogeneity by heating B. pertussis cells for 1 h at 60 degrees C followed by DEAE-Sepharose and Affi-Gel Blue chromatography. Antibodies found in sera obtained from patients diagnosed as having pertussis reacted with this protein. This purification scheme should be useful for the production of the 69 kDa protein which is currently being evaluated as a pertussis vaccine candidate.

Antibodies to Bordetella pertussis adenylate cyclase toxin in neonatal and maternal sera.

To investigate the high prevalence among infants of antibodies to Bordetella pertussis adenylate cyclase toxin (ACT), cord-blood sera were examined for antibodies to ACT, filamentous hemagglutinin (FHA) and pertussis toxin (PT) using immunoblot analysis. Antibodies reactive with ACT were the most prevalent in neonatal sera. Similar reactivity of IgG with ACT was found in each sample of a given neonatal-maternal pair, yet IgM reactive with ACT was virtually absent in neonatal sera, suggesting that antibodies to ACT are maternally derived. Antibodies to ACT might come from infection or childhood vaccination of the mothers since pertussis vaccines from all US manufacturers elicited antibodies to ACT in mice. Alternatively, these antibodies may have been elicited by a cross-reactive antigen such as Escherichia coli alpha-hemolysin, since all of the neonatal and maternal sera contained antibodies reactive with alpha-hemolysin.

Parenteral iron dextran therapy: a review.

Iron dextran was introduced more than 30 yr ago for the parenteral treatment of iron deficiency anemia that is refractory to oral therapy. Iron dextran is a preparation of ferric hydroxide complexed with a low molecular weight fraction of dextran. Iron deficiency anemia is one of the most common nutritional deficiency diseases and occurs worldwide secondary to inadequate dietary iron, usually with excessive gastrointestinal blood losses. Repletion of iron stores is often complicated by intolerance to oral iron supplementation and may require parenteral iron. Parenteral iron can be administered via the intramuscular or intravenous route either directly or as an additive to total parenteral nutrition. Both routes of administration can cause various side effects and a test dose is recommended before therapeutic administration to assess the risk for anaphylaxis. Although the efficacy and safety of parenteral iron dextran have been convincingly demonstrated, supplementation may be contraindicated in the setting of infection.

Effect of iron-supplemented total parenteral nutrition in patients with iron deficiency anemia.

Iron deficiency anemia is common among hospitalized patients, and blood losses from diagnostic phlebotomy increase the likelihood of a negative iron balance. The role for iron supplementation of total parenteral nutrition (TPN) in these patients is unclear. Twenty-three patients with iron deficiency anemia were identified. Twelve patients were randomized to receive TPN without iron (group 1) and 11 received TPN supplemented with 10 mg of iron as iron dextran daily (group 2). Both groups were matched for age, serum iron studies, red cell indices, and hemogram. After a 7-d period, the mean serum iron in group 2 increased from 10 to 26 micrograms/dL, with an increased transferrin saturation from 7.3 to 15.3% (each, p < 0.05). No changes in total iron binding capacity, ferritin, reticulocyte count, hemoglobin, hematocrit, or mean corpuscular volume were observed in the two groups. The incidence of infectious complications was not different between both groups. We conclude that iron supplementation of TPN appears safe and is effective in increasing serum iron levels. The use of iron-supplemented short-term TPN needs to be further studied given no change in red cell indices, hemoglobin, hematocrit, or transfusion requirement.

Positive toxicology screening in newborns: ethical issues in the decision to legally intervene.

Perinatal substance abuse causes a host of problems including physical and psychological impairments to a developing fetus. However, responding to the needs of pregnant women who use drugs and their children poses an additional challenge in this already deplorable situation. Foster care, adoption, criminalization, and reunification are all possibilities as intervention options in this dilemma. Each of these options prompts additional problems for mother, child, and provider. What was once uncommon or uncontroversial for public health nursing is now bringing a new wave of discussions in the health system and nurses need to be cognizant of the ramifications of delivering care to perinatal substance abusing mothers and their families. Assessment, planning, intervention, and evaluation--the nursing process--emerges as an invaluable tool.

Biochemical properties of pertussis toxin.

Pertussis toxin is an exotoxin produced by the organism Bordetella pertussis. The toxin binds to receptors on the eukaryotic cell surface. After introduction into the eukaryotic cell, the toxin is activated by ATP and subsequently ADP-ribosylates a family of GTP-binding regulatory proteins interrupting signal transduction within the cell. We have examined the location of several critical sites on the toxin molecule. These sites include the receptor binding site and the ATP binding site. The B oligomer of the toxin was found to contain at least two sites capable of binding glycoproteins suggesting that the B oligomer may have more than one eukaryotic cell receptor binding site. ATP was also shown to bind to a site on the B oligomer. These results indicate that the B oligomer contains several sites necessary for toxin action.

Structural and functional properties of a 69-kilodalton outer membrane protein of Bordetella pertussis.

A-69-kDa outer membrane protein present on virulent Bordetella pertussis cells is recognized by the agglutinating monoclonal antibodies BPE3, BPD8, and BPE8. The amino acid composition of this protein, purified from heat extracts of B. pertussis BP353 cells, is different from that of the two major fimbrial antigens of B. pertussis, which is consistent with its being a nonfimbrial protein based on other criteria. Western blot analysis using the monoclonal antibody BPE3 demonstrated that a slightly larger but antigenically cross-reactive protein is also expressed by Bordetella bronchiseptica and Bordetella parapertussis. In addition, a large molecular weight species of about 180-kDa is found in outer membrane extracts of B. bronchiseptica which may represent a precursor form of the protein or indicate that the protein can exist as an oligomer. The monoclonal antibody BPD8 directed against the 69-kDa protein almost completely inhibited the enzymatic activity of adenylate cyclase purified from B. pertussis and also inhibited the intoxication of mammalian cells by this enzyme. Since little enzymatic activity was found associated with the purified 69-kDa protein, these data suggest a role for the 69-kDa protein in regulating the adenylate cyclase toxin of B. pertussis. An additional monoclonal antibody directed against the 69-kDa protein, BPE8, decreases lymphocytosis and delays death in mice receiving a respiratory challenge of virulent B. pertussis cells. These studies suggest that further investigation into the role of this protein as a protective antigen and vaccine candidate is warranted.

International Bordetella pertussis assay standardization and harmonization meeting report. Centers for Disease Control and Prevention, Atlanta, Georgia, United States, 19-20 July 2007.

An international meeting on Bordetella pertussis assay standardization and harmonization was held at the Centers for Disease Control and Prevention (CDC), Atlanta, GA, 19-20 July 2007. The goal of the meeting was to harmonize the immunoassays used for pertussis diagnostics and vaccine evaluation, as agreed upon by academic and government researchers, regulatory authorities, vaccine manufacturers, and the World Health Organization (WHO). The primary objectives were (1) to provide epidemiologic, laboratory, and statistical background for support of global harmonization; (2) to overview the current status of global epidemiology, pathogenesis and immunology of pertussis; (3) to develop a consensus opinion on existing gaps in understanding standardization of pertussis assays used for serodiagnosis and vaccine evaluation; and (4) to search for a multicenter process for addressing these priority gaps. Presentations and discussions by content experts addressed these objectives. A prioritized list of action items to improve standardization and harmonization of pertussis assays was identified during a group discussion at the end of the meeting. The major items included: (1) to identify a group that will organize, prepare, maintain, and distribute proficiency panels and key reagents such as reference and control sera; (2) to encourage the development and identification of one or more reference laboratories that can serve as an anchor and resource for other laboratories; (3) to define a performance-based assay method that can serve as a reference point for evaluating laboratory differences; (4) to develop guidance on quality of other reagents, e.g., pertussis toxin and other antigens, and methods to demonstrate their suitability; (5) to establish an international working group to harmonize the criteria to evaluate the results obtained on reference and proficiency panel sera; (6) to create an inventory to determine the amount of appropriate and well-characterized sera that are available globally to be used as bridging reagents for vaccine licensure; and (7) to seek specific guidance from regulatory authorities regarding the expectations and requirements for the licensure of new multicomponent pertussis vaccines.

Capsule endoscopy findings in celiac disease associated enteropathy-type intestinal T-cell lymphoma.

Capsule endoscopy is a new technology developed to investigate diseases of the small intestine. It has been shown to be superior to current modalities such as small-bowel radiography and enteroscopy. We describe a patient with long-standing celiac disease who presented with abdominal pain, diarrhea, and weight loss, after many years on a gluten-free diet. The symptom complex and results from small-bowel radiography and computerized tomography raised concern about progression to lymphoma, and ultimately a laparoscopy and small-bowel resection were done for diagnosis. A capsule endoscopy was performed to assess the extent of the patient's enteropathy-type intestinal T-cell lymphoma after three cycles of chemotherapy. We report the first use of capsule endoscopy in the setting of celiac disease associated enteropathy-type intestinal T-cell lymphoma. These endoscopic findings are correlated with those from gross and microscopic pathology and barium small-bowel radiography.

Subunit structure and enzymic activity of pertussis toxin.

Pertussis toxin, an ADP-ribosylating toxin, interacts with vertebrate cells of many types and inhibits the ability of these cells to respond to certain hormones and neurotransmitters, resulting in a multitude of biological effects. The structure and mechanism of action of this toxin are described.