Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine.

BACKGROUND: Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated. METHODS: Adult surgical patients (ASA class I-III) were randomized to sugammadex 2.0 mg kg(-1) for reversal of block induced by rocuronium 0.6 mg kg(-1), or neostigmine 50 microg kg(-1) for reversal of block induced by cisatracurium 0.15 mg kg(-1). Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch SX). Sugammadex or neostigmine was administered at reappearance of T(2). The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine (geometric mean=1.9 vs 9.0 min, P<0.0001). Reversal of block was sustained in all patients. There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety, except for similar elevations in urinary N-acetyl glucosaminidase in both groups. CONCLUSIONS: Sugammadex 2.0 mg kg(-1) administered at reappearance of T(2) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.

Activated ras genes in human seminoma: evidence for tumor heterogeneity.

The incidence of mutations in cellular ras genes was determined in human seminoma, a germ cell tumor of the testis, with the aid of specific oligonucleotide probe hybridization. To eliminate the large number of nonneoplastic cells present in seminomas, aneuploid tumor cell nuclei were isolated from the tumor tissue by flow sorting. Mutations were detected in 40% of the seminomas at codons 12 or 61 of either the Ki-ras or the N-ras gene. No correlation was found with histopathological or clinical features. In some seminomas the mutant gene was present in only a fraction of the tumor cell population, suggesting tumor heterogeneity for ras gene mutations. Yet, flow cytometric measurement of nuclear DNA contents and histological examination of tumor tissue did not reveal two different tumor cell populations. We conclude from these observations that ras mutation is probably not the initial genetic event in the development of seminoma.

Philadelphia chromosome-positive thrombocythemia and megakaryoblast leukemia.

A case of well-documented and -illustrated megakaryoblastic transformation is described in a patient with thrombocythemia passing through a stage of myelofibrosis without features of chronic granulocytic leukemia. Immunocytologic studies with the use of conventional and monoclonal antibodies against platelet membrane glycoproteins and electron microscopic investigations, demonstrating bull's-eye granules and platelet peroxidase positivity, proved the megakaryocytic differentiation of the blast cells. From the onset of the disease as well as during the megakaryoblastic transformation, the Philadelphia (Ph1) karyotype, 46XX t(9:22) (q34:q11), was found in peripheral blood and bone marrow cells as the only clonal abnormality. Southern blot analysis of DNA extracted from the blast cells revealed a rearrangement within the bcr on chromosome 22 similar to findings in chronic granulocytic leukemia. The presentation with excessive small and abnormal megakaryocytes in the initial and subsequent bone marrow and the rapid progressive myelofibrosis and splenomegaly differentiate the Ph1 chromosome-positive thrombocythemia from the chronic myeloproliferation of thrombocythemia in its primary form or associated with polycythemia vera.

Immunologic marker analysis of normal and malignant histiocytes. A comparative study of monoclonal antibodies for diagnostic purposes.

The authors investigated the phenotype of "monocyte-derived histiocytes/macrophages" on frozen sections of various human tissues, in 12 histiocytic tumors, and in 15 large cell non-Hodgkin's lymphomas. The monoclonal antibodies (MAbs) considered specifically directed against antigens associated with monocytes/histiocytes included the following: Leu-M1, Leu-M3, Leu-M5, My4, My7, My8, My9, anti-Monocyte 1, anti-Monocyte 2, RFD-7, RFD-9, OKM1, and FMC17. The histiocytes in normal tissues and the tumor cells of the histiocytic malignancies expressed these antigens in various degrees. They were not reactive with MAbs specific for lymphocytes, myeloid cells, or Reed-Sternberg cells (Ki-1 antigen). Out of these 13 MAbs, only the labeling by MAb Leu-M3, Leu-M5, anti-Monocyte 1, and RFD-7 was restricted to normal and malignant monocytes/histiocytes. In combination with their broad labeling of different types of monocytes/macrophages, these MAbs are of value in differential diagnostic purposes to distinguish histiocytic malignancies from large cell lymphomas. However, none of the 13 MAbs can be considered as pan-histiocytic reagents because they did not recognize all cell types belonging to the mononuclear/phagocytic system.

Thrombocythaemic erythromelalgia in chronic myeloproliferative and myelodysplastic disorders.

Erythromelalgia, which is specific for primary thrombocythaemia or polycythaemia with thrombocythaemia, is reported in a case of primary myelofibrosis at platelet counts of between 350 and 450 X 10(9)/l. In addition, the unexpected occurrence of thrombocythaemic erythromelalgia associated with Ph1 chromosome positive micromegakaryocytic myelofibrosis and with myelodysplastic syndrome type II is described. Therefore it is concluded that erythromelalgia may occur in all variants of myeloproliferative disease as well as myelodysplastic syndrome as long as they present with thrombocythaemia.

[Diagnosis and treatment of malignant histiocytosis]. / Diagnostiek en behandeling van maligne histiocytose.

Of twelve patients with malignant histiocytosis admitted between 1974 and 1987, clinical symptoms, diagnostic procedures and the course of the disease were retrospectively evaluated. Predominant findings at physical examination were fever (11/12), splenomegaly (12/12), hepatomegaly (8/12), and lymphadenopathy (8/12). Laboratory findings included anaemia, leukocytopenia, thrombocytopenia, high lactate dehydrogenase, and jaundice. Positive diagnostic procedures included biopsies or aspirates of bone marrow (11/12), spleen (6/10), liver (7/9), lymph node (4/4), skin (1/2), lung (1/1) and blood (2/12). In seven patients treated with combination chemotherapy an average survival of 540 days was observed, while two long-term disease-free survivals were accomplished.

[Unexplained lymphadenopathy: Whipple disease]. / Onbegrepen lymfadenopathie: ziekte van Whipple.

A 58-year-old man was referred to the internal medicine outpatient department because of abdominal pain and lymphadenopathy. CT imaging revealed multiple mediastinal, para-aortic, mesenteric and pelvic lymphoma. Biopsy of an inguinal lymph node for histology purposes revealed granulomatous lymphadenitis. A watchful waiting approach was adopted. Two and a half years after first presentation, the patient presented with weight loss, fever and night sweats. CT imaging showed progressive lymphadenopathy and hepatosplenomegaly. Histopathological examination of a laparoscopically removed lymph node showed extensive infiltration with macrophages with stained rod-shaped bacteria (periodic acid-Schiff staining), which is typical of Whipple disease. PCR and biopsies of the small intestine confirmed the diagnosis. Antibiotic therapy was started with rapid clinical and biochemical improvement. A year later PCR of the duodenal biopsies was negative and the antibiotics were discontinued. Whipple disease is a rare chronic infection caused by Tropheryma whipplei. Clinical symptoms can vary, so it often takes a long time to diagnose.

Assessment of genotypic diversity of antibiotic-producing pseudomonas species in the rhizosphere by denaturing gradient gel electrophoresis.

The genotypic diversity of antibiotic-producing Pseudomonas spp. provides an enormous resource for identifying strains that are highly rhizosphere competent and superior for biological control of plant diseases. In this study, a simple and rapid method was developed to determine the presence and genotypic diversity of 2,4-diacetylphloroglucinol (DAPG)-producing Pseudomonas strains in rhizosphere samples. Denaturing gradient gel electrophoresis (DGGE) of 350-bp fragments of phlD, a key gene involved in DAPG biosynthesis, allowed discrimination between genotypically different phlD(+) reference strains and indigenous isolates. DGGE analysis of the phlD fragments provided a level of discrimination between phlD(+) genotypes that was higher than the level obtained by currently used techniques and enabled detection of specific phlD(+) genotypes directly in rhizosphere samples with a detection limit of approximately 5 x 10(3) CFU/g of root. DGGE also allowed simultaneous detection of multiple phlD(+) genotypes present in mixtures in rhizosphere samples. DGGE analysis of 184 indigenous phlD(+) isolates obtained from the rhizospheres of wheat, sugar beet, and potato plants resulted in the identification of seven phlD(+) genotypes, five of which were not described previously based on sequence and phylogenetic analyses. Subsequent bioassays demonstrated that eight genotypically different phlD(+) genotypes differed substantially in the ability to colonize the rhizosphere of sugar beet seedlings. Collectively, these results demonstrated that DGGE analysis of the phlD gene allows identification of new genotypic groups of specific antibiotic-producing Pseudomonas with different abilities to colonize the rhizosphere of sugar beet seedlings.

An unusual cause of acute appendicitis.

A case is presented of a patient with a metastasis of cardia carcinoma to the appendix, causing acute appendicitis. Survey of the literature shows that metastasis to the appendix is very rare. When present, it is likely to be the cause of appendicitis by obstruction of the lumen.

The mechanism of inhibition of haemopoiesis in acute leukaemia.

One characteristic feature of human acute leukaemia is a depression of normal haemopoiesis which, according to the results of in vitro colony formation, seems to be more severe in acute myeloid leukaemia (AML) than in acute lymphocytic leukaemia (ALL). In our rat model for AML, the transplantable Brown Norway myeloid leukaemia (BNML), near total suppression of haemopoiesis was observed in a relatively early stage of the disease because of the physical disappearance of haemopoietic stem cells (HSC) from the bone marrow, which was only partly compensated by an increased number of HSC in the spleen. The few HSC remaining in the BNML bone marrow in the terminal stage of the disease were mostly out of cycle, in contrast to the HSC in normal rat marrow. Studies with injected labelled leukaemic cells revealed that both BNML and cells of a transplantable lymphatic leukaemia home in the subendosteal region of the femoral bone marrow. Subsequently, ALL cells become randomly distributed over the whole marrow space, while BNML cells remain localized in the subendosteal region. The latter area contains in normal rat marrow a higher proportion of proliferating blast cells than the central area of the marrow, which is reminiscent of the kinetic gradient described in mouse bone marrow by Shackney et al. [22]. These observations support the hypothesis that the depression of normal haemopoiesis in AML is caused by a specific localization and proliferation of AML cells in the subendosteal area, which normally provides the optimal microenvironment for HSC self-replication. In ALL the more severe depression of haemopoiesis occurs in a later stage and is caused by random replacement of HSC as a result of non-specific overgrowth.

Congenital self-healing non-Langerhans cell histiocytosis.

Clinical, morphological, ultrastructural and immunological studies were performed in a case of congenital self-healing non-Langerhans cell histiocytosis. The patient showed several aspects that have not been published before: a large nodule in the vulvar region, vesiculobullous elements and pneumonia (asymptomatic). The relationship of the vesicles and pneumonia to the histiocytic disorder is not clear. Ultrastructurally, worm-like (comma-shaped) particles, dense bodies and Birbeck granules were not found. Histiocytes were Leu-6 negative, and S100 (partly), Leu M3 and HLA-DR positive. Positive reactions were also obtained with anti-lysozyme and non-specific esterase. Several aspects of this case and of others described previously are discussed.

Markers of immunologic injury in progressive alopecia areata.

In a selected group of 8 patients with progressive alopecia areata (AA) leading to AA universalis, immunological aspects (in the peripheral blood and the tissue) were studied during the period of the initial attack of the disease. The peripheral T-cell helper/suppressor ratio appeared not to be a reliable parameter for the disease activity. The intrabulbar and peribulbar distribution of T-cells, Langerhans cells and of HLA-DR expression in and around the anagen hair follicles in the progressive areas of the disease (region of exclamation-mark hairs) may suggest a T-cell-mediated injury primarily in the peribulbar regions of the follicles. The data presented tend to support the possibility that in the early development of AA, the dermal pailla (capillary network?) may be the prime target of immunologic injury.

Clinicopathological diagnosis and treatment of malignant histiocytosis.

The diagnostic findings of malignant histiocytosis (MH) were analysed in 12 consecutive patients in a single institution. Most patients presented with systemic symptoms and lymphadenopathy (92%), splenomegaly (100%) and hepatomegaly (67%). Neurologic symptoms were present in three patients, while involvement of other organs was present in five patients. The incidence of severe thrombocytopenia was 92% of anaemia 92% and of leucocytopenia 67%. Serum angiotensin converting enzyme, alpha 1-antitrypsin and lysozyme were independently increased in 6/9, 3/10 and 1/9 patients respectively. High serum levels of tumour necrosis factor (TNF) were present in 3/10 patients, while serum levels of interleukin-1 were normal in 10/10 patients. Histologic evidence of MH was obtained in all patients by repeated biopsies of involved tissues. Four patients died prior to treatment. Seven patients were treated with combination chemotherapy, consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or MOPP (chloromethine, vincristine, procarbazine, prednisone), in some cases followed by non-cross-resistant second line chemotherapy, if no complete response was attained. The response rate of treated patients was 57%, and progression was observed in two patients. The median duration of response was 38 months. Three patients are alive without evidence of disease and off therapy (30+, 83+, 85+ months). Although MH is a potentially lethal disease, combination chemotherapy may offer a chance for cure in some patients.

The effect of high doses of poly(I).poly(C) induced mouse L cell interferon on Rauscher leukemia virus induced erythroleukemia in BALB/c mice.

The effect of high doses of poly(I).poly(C) induced mouse L-cell interferon on the development of Rauscher murine leukemia virus (R-MuLV)-induced erythroleukemia in BALB/c mice was determined. Female mice, 4 to 5 weeks old, were infected with R-MuLV and treated with interferon every 24 h starting 6 h after virus inoculation. Under these conditions injection of 3-5 X 10(4) units of interferon caused a partial inhibition of the leukemia process. Daily application of 3 X 10(5) units completely or almost completely inhibited the erythroleukemia. After 14 days of treatment with these high doses of interferon, spleen weights of interferon-treated infected mice were comparable to those of uninfected animals which received only interferon. Also, no Rauscher cells in spleens and livers of R-MuLV-infected interferon-treated infected animals could be demonstrated and the spleen structure was well preserved in these mice. In interferon-treated infected animals no virus could be detected in the serum as judged from the absence of reverse transcriptase activity in the serum. Moreover, no virus-infected cells could be demonstrated in spleen or liver as deduced from negative immunofluorescence data using anti-p30 and anti-gp70 sera. No virions budding from spleen cell membranes were seen by electron microscopic studies. However, when interferon treatment was stopped the leukemic process was reactivated and all the mice died. In control experiments interferon caused an inhibition of red blood cell formation and a 50 to 100% enlargement of the spleen. Pharmacokinetic data showed that, after intraperitoneal inoculation, maximum amounts of interferon were present in the peripheral blood after 1-2 h. After 12-24 h almost all interferon activity had disappeared from the blood.