Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO‐incompatible pancreas and kidney transplantation

Summary We describe the presumably first intentional ABO‐incompatible deceased‐donor kidney and pancreas transplantation with a severe antibody‐mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement‐related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.     

Comparison of the performance of rapid HIV tests using samples collected for surveillance in Mozambique

Mozambique had low HIV prevalence until the mid‐1990s, but recent data indicate increasing rates. There is little information on HIV‐2. Therefore, HIV seroprevalence was assessed among pregnant women and field‐ready HIV diagnostic strategies were evaluated. A total of 6,930 samples collected by three health centers from 2002 to 2005 were tested on site by nurses with two simple/rapid tests, Determine HIV‐1/2 (Abbott Laboratories; screening) and Uni‐Gold HIV (Trinity Biotech; confirmation), which is the national HIV testing strategy. The prevalence of HIV was 14.0% (2002), 17.8% (2003), 16.5% (2004), and 20.2% (2005). A subset of 888 samples collected 2003 was sent to the Central Microbiology Laboratory, Maputo for evaluation of tests and testing strategies. The assays included for comparison were Capillus HIV‐1/HIV‐2 (Trinity Biotech), DoubleCheckGold HIV‐1&2 (Orgenics) and Enzygnost Anti‐HIV‐1/2 Plus (Behringwerke, reference ELISA). Confirmation of reactive samples was done by Uni‐Gold HIV and ImmunoComb II HIV‐1&2 BiSpot (for HIV type differentiation). The Capillus HIV‐1/ HIV‐2 + ImmunoComb II HIV‐1&2 BiSpot combination was the gold standard. The sensitivity of the rapid/simple screening assays (Determine HIV‐1/2, DoubleCheckGold HIV‐1&2) was 100% (N = 160) and their (initial) specificities were 99.6% and 99.7%, respectively. Repeated testing and combinations of assays increased the specificity. Four suspected cases of recent seroconversion were found. Together with the increasing prevalence rates, this may indicate that Mozambique is a high‐incidence area, although further studies are needed to confirm this. Testing strategies for on‐site screening and confirmation based on the combination of Determine HIV‐1/2, Uni‐Gold HIV and DoubleCheckGold HIV‐1&2 are well suited for local field use. J. Med. Virol. 81:1991–1998, 2009. © 2009 Wiley‐Liss, Inc.     

Long-term Results of the Tension-Free Vaginal Tape (TVT) Procedure for Surgical Treatment of Female Stress Urinary Incontinence

In a prospective long-term Nordic multicenter study, 90 consecutive patients who had a tension-free vaginal tape (TVT) operation performed because of stress urinary incontinence were evaluated according to a strict protocol after approximately 5 years (range 48-70 months). Eighty-five patients could be evaluated according to the protocol. Another 5 elderly patients had to be interviewed by telephone at the final check-up after 5 years. The study protocol involved pre- and postoperative objective and subjective evaluation. The median follow-up time was 56 months. Seventy-two of the 85 patients who were fully evaluated (84.7%) were both objectively and subjectively completely cured. Another 9 patients (10.6%) were significantly improved and 4 (4.7%) were regarded as failures. No patient complained of long-term voiding difficulties and there were no signs of defective healing or rejection of the tape material. All patients had suffered from primary stress incontinence, and 25 also had preoperative complaints of urge. In 14 of these (56%) the urge symptoms were relieved postoperatively. We conclude that the TVT procedure seems to fulfil the expectations of high long-term cure rates, as suggested in previous short-term reports.     

Quantitative assessment of a human carcinogenic potency for propylene oxide

The potential for causing carcinogenic and mutagenic effects is the main concern when assessing the risks associated with low-level exposures of humans to the industrially important epoxide, propylene oxide (PO). The available basic information used in estimation of carcinogenic risk has been reviewed. It is concluded that the published data from gavage studies in rodents are less appropriate and that observed cancer incidences from long-term inhalation should preferably be utilized for quantitative risk assessment. Furthermore, PO and ethylene oxide (EO) are directly acting alkylating agents which exhibit several similarities. Although data are less comprehensive for PO than for EO, PO appears to yield a rather uniform alkylation pattern in various tissues. Also, similarly to EO, PO is probably detoxified at a rate which does not vary widely in various mammalian species, including man. For these reasons, the surface-based extrapolation model for estimation of the human equivalent dose may not be appropriate, and the previously derived carcinogenic potency factors should be revised downward. Alternative risk estimates are provided. From the most relevant available studies, we propose a carcinogenic potency factor of 0.001 (mg/kg/day)-1 for PO in humans by inhalation.     

Successful retrieval of fine-needle aspiration biopsy material from previously stained smears for immunocytochemistry: a novel technique applied to three soft tissue tumors.

Fine-needle aspiration biopsies of soft tissue tumors are often not fully diagnostic on conventional Papanicolaou or Giemsa stains. Often, more useful information can be gleaned from preparing cell blocks, which are amenable to immunocytochemistry. However, sufficiently diagnostic cell block material is not always forthcoming. We subvent this problem by employing a new 'cytoscrape' technique to create cell blocks from previously Papanicolaou-stained smear material in two cases of mesenchymal tumors where smear diagnoses were limited to 'sarcoma, not otherwise specified'. After thorough text and photographic documentation of the smear results, the slides were decolorized and tumor cells were removed for processing as for routine preparation of cell blocks. Sections cut were then submitted for immunocytochemical profiling. This resulted in definitive diagnoses in both cases, averting the need for more invasive diagnostic procedures. We applied the same technique to a third case of a lung nodule, in which the smear was inconclusive and the original cell block nondiagnostic. The subsequent immunocytochemical testing enabled a definitive diagnosis to be made. This novel technique is described here; its value and applicability are discussed in the context of fine-needle aspiration biopsies of soft tissue tumors.     

Iodide handling by the thyroid epithelial cell.

Iodination of thyroglobulin, the key event in the synthesis of thyroid hormone, is an extracellular process that takes place inside the thyroid follicles at the apical membrane surface that faces the follicular lumen. The supply of iodide involves two steps of TSH-regulated transport, basolateral uptake and apical efflux, that imprint the polarized phenotype of the thyroid cell. Iodide uptake is generated by the sodium/iodide symporter present in the basolateral plasma membrane. A candidate for the apical iodide-permeating mechanism is pendrin, a chloride/iodide transporting protein recently identified in the apical membrane. In physiological conditions, transepithelial iodide transport occurs without intracellular iodination, despite the presence of large amounts of thyroglobulin and thyroperoxidase inside the cells. The reason is that hydrogen peroxide, serving as electron acceptor in iodide-protein binding and normally produced at the apical cell surface, is rapidly degraded by cytosolic glutathione peroxidase once it enters the cells. Iodinated thyroglobulin in the lumen stores not only thyroid hormone but iodine incorporated in iodotyrosine residues as well. After endocytic uptake and degradation of thyroglobulin, intracellular deiodination provides a mechanism for recycling of iodide to participate in the synthesis of new thyroid hormone at the apical cell surface.     

Adrenergic innervation and neurogenic response in large and small arteries and veins from the rat

A combined morphological and physiological analysis of the properties of the adrenergic vasoconstrictor innervation was carried out in the splanchnic vasculature in the rat. Three generations of vessels were studied: (1) the abdominal aorta and the caval vein; (2) the superior mesenteric artery and vein; (3) 200 microns branches of the superior mesenteric artery and their parallelling veins. The adrenergic innervation was visualized by the Hillarp-Falck fluorescence technique, and by the immunohistochemical localization of immunoreactivity to tyrosine hydroxylase and dopamine-beta-hydroxylase. Determination of responses to applied noradrenaline, to transmural nerve stimulation and to direct activation of the muscle was made on ring preparations mounted in a myograph. All vessels were found to be innervated at the adventitio-medial border by noradrenergic nerves with varying density; the small arteries had the highest nerve density, the abdominal aorta was least innervated. When related to the maximal isometric response to applied noradrenaline, the maximal neurogenic response parallelled the density of the adrenergic innervation. Variations in frequency for half-maximal response among the vessels could not, however, be ascribed to innervation properties only. The constriction under isotonic conditions amounted to 20% of the initial circumference in the aorta, and to 30% in the small arteries and veins. The relation between response to applied noradrenaline and to nerve stimulation was similar for isometric and isotonic responses. In the smaller veins, a beta-receptor-mediated decline in the response to applied noradrenaline was seen. This decline was much less pronounced in neurogenic responses. The results indicate a gradation from proximal to peripheral arteries towards denser innervation and greater neurogenic responses. On the venous side only minor differences were found.