Biomedical subjects

J Jansen

Publications and source records attributed to J Jansen.

At least 91 records · Page 5Linked to original sources

PubMed1995

Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2).

BACKGROUND & AIMS: Increased concentrations of tumor necrosis factor (TNF), a potent proinflammatory cytokine, can be shown in the mucosa of patients with active Crohn's disease. Neutralization of TNF has been shown to decrease recruitment of inflammatory cells and granuloma formation in several animal models. The aim of this study was to investigate the safety and potential efficacy of an anti-TNF monoclonal antibody in the treatment of active Crohn's disease. METHODS: Ten patients with active Crohn's disease that was unresponsive to therapy were administered a single infusion of an anti-TNF human/mouse chimeric monoclonal antibody (cA2) in an open-label treatment protocol while the baseline anti-inflammatory therapy was continued. RESULTS: Eight patients showed normalization of Crohn's Disease Activity Index scores and healing of ulcerations as judged by colonoscopy within 4 weeks after treatment. One patient had a perforation after colonoscopy and recovered completely after surgery. One elderly patient showed a poor response. The average duration of response after a single infusion was 4 months. No adverse experiences related to cA2 were observed. CONCLUSIONS: The results support the hypothesis that TNF is of major importance in the pathogenesis of Crohn's disease. Treatment with cA2 was safe and may be useful in patients with Crohn's disease that is unresponsive to steroid treatment.

Adult↗

PubMed1995

Maturation of mobilized peripheral blood progenitor cells: preclinical and phase I clinical studies.

The use of mobilized peripheral blood progenitor cells (PBPC) after high-dose chemotherapy has markedly decreased the period of severe neutropenia. In an attempt to further decrease the duration of neutropenia, the potential of PBPC to mature during in vitro culture was assessed, with special attention being paid to culture medium, growth factors, and cell concentration. Concentrations of 10(6) PBPC/mL resulted in better recovery than 10(7)/mL as far as total cells, CFU-GM, and granulocytes were concerned. The combination of IL-3 + GM-CSF+G-CSF appeared to be better than any of these growth factors alone. Simple media, such as Medium 199, gave poorer cell recovery than more complex media, such as IMDM. With 10(6)/mL nonenriched PBPC in IMDM with IL-3/GM-CSF/G-CSF, on day 15 CFU-GM reached 450% of the initial level. At that point, granulocytes had increased 15-fold. A small phase I study was performed to assess the toxicity of infusing 1000-2000 mL of PBPC cultured for 3 days at 3-10 x 10(6)/mL with IL-3/GM-CSF/G-CSF in LifeCell bags. Although no clear decrease in the duration of neutropenia was observed, the infusions were uncomplicated in 5 of the 6 patients and had minor side effects in the sixth patient. These data suggest that in vitro differentiation of nonenriched PBPC is possible. However, to develop a clinically applicable method, several logistical problems will have to be overcome.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Frozen section consultation. Utilization patterns and knowledge base of surgical faculty at a university hospital.

The authors studied the knowledge base of surgical faculty concerning frozen section consultations at a university hospital to determine whether it had any relationship to the appropriateness of frozen section requests. To accomplish this, the reasons for performing frozen sections during a 3-month period were analyzed, and those request that seemed ambiguous or inappropriate were identified. Simultaneously a 15-item questionnaire was distributed to faculty and housestaff dealing with factual information concerning the technique and limitations of frozen section diagnosis (Questions 1-8), as well as appropriateness of frozen section requests in a number of clinical situations (Questions 9-15). The collective score on items of general information (Questions 1-8) was 69%, whereas scores on Questions 9-15 ranged from 39% on the gynecologic question related to evaluation of a cystic ovarian mass to 81% on the general surgery question regarding evaluation of a soft tissue mass. Of 914 frozen sections, 95% were performed for appropriate reasons, which included evaluation of margins (46%), establishing a primary diagnosis (43%), determining adequacy or viability of tissue (3%), or satisfying immediate patient/family concerns ( < 1%). Five percent of frozen sections were performed for ambiguous or seemingly inappropriate reasons. Because fewer than five faculty members were responsible for the inappropriate frozen section request, the authors did not find that the results of the questionnaire predicted or anticipated situations in which inappropriate requests occurred. Nonetheless, the results of the questionnaire indicate there is important general information concerning frozen sections that is not uniformly shared by surgical faculty, such as the types of tissue that cannot be cut on a cryostat, the reasons for deferred frozen sections, and the situations in which fresh tissue is needed for special studies. The authors suggest the inappropriate frozen section could be diminished by an educational initiative targeted at a relatively small segment of clinical faculty, whereas enhancement of general information regarding frozen section should ideally occur in the broader context of clinical conferences using illustrative case material.

Faculty↗

PubMed1995

Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein.

To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature. The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1-antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23. The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans.

Antimicrobial Cationic Peptides↗

PubMed1995

Effect of postponed treatment with an anti-tumour necrosis factor (TNF) F(ab')2 fragment on endotoxin-induced cytokine and neutrophil responses in chimpanzees.

TNF is considered to be an intermediate factor in endotoxin-induced release of other cytokines and endotoxin-induced neutrophil degranulation. Little is known about the effect of postponed treatment with anti-TNF in primate endotoxin models. To assess the effect of delayed treatment with anti-TNF in endotoxaemia, six healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg). In three of these animals the administration of endotoxin was followed after 30 min by a bolus i.v. injection of the anti-TNF F(ab')2 fragment MAK 195F (0.1 mg/kg). Post-treatment with MAK 195F completely prevented the appearance of TNF activity in serum elicited by endotoxin, and markedly reduced the rises in the serum concentrations of IL-6 and IL-8. In addition, the endotoxin-induced increases in the type I and type II soluble TNF receptors were also profoundly inhibited by MAK 195F, suggesting that TNF is involved in the release of its own soluble receptors in endotoxaemia. Neutrophilic leucocytosis was not affected by MAK 195F. In contrast, MAK 195F did significantly abrogate neutrophil degranulation, as measured by the plasma concentrations of lactoferrin. These results indicate that treatment with anti-TNF 30 min after the administration of endotoxin is still effective in attenuating the induction of the cytokine network and of neutrophil degranulation.

Animals↗

PubMed1995

Modulation of cytokine release from human monocytes by drugs used in the therapy of inflammatory bowel diseases.

BACKGROUND: Cytokines produced in the gut mucosa play an important role in the pathogenesis of inflammatory bowel diseases (IBD). To determine whether drugs used in the treatment of these diseases modulate cytokine synthesis, we investigated their effects on endotoxin-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 release by elutriation-purified human monocytes in vitro. METHODS: Drugs tested were dexamethasone, 5-aminosalicylic acid, sulphapyridine and zileuton (a 5-lipoxygenase inhibitor). Monocytes were isolated and stimulated with endotoxin, and TNF, IL-1 and IL-6 levels were determined using an enzyme-linked immunosorbent assay. RESULTS: Monocyte stimulation with endotoxin resulted in an average TNF release of 2464 +/- 64 pg/10(6) cells, IL-1 release of 616 +/- 47 pg/10(6) cells and IL-6 release of 2259 +/- 148 pg/10(6) cells. Addition of dexamethasone resulted in a reduction of TNF, IL-1 and IL-6 release to below background levels. Sulphapyridine significantly reduced TNF and induced IL-1 release in a dose-dependent fashion, but had no significant effect on IL-6 release. 5-Aminosalicylic acid did not modulate IL-6 synthesis, but significantly reduced IL-1 and enhanced TNF synthesis. Zileuton reduced TNF and IL-6 release, but enhanced IL-1 release. CONCLUSION: We conclude that these anti-inflammatory drugs are able to modulate cytokine release by human monocytes. Further studies are needed to determine whether these effects are related to their therapeutic efficacy in IBD.

Aminosalicylic Acids↗

PubMed1995

The t(15;17) translocation in acute promyelocytic leukemia.

Retinoic acid (RA) is a vitamin A derivative with striking effects on development and cell differentiation. The identification of three RA receptors (RAR alpha, beta and gamma) as members of the nuclear receptor superfamily led to important insights into the molecular mechanism of action of retinoids. The nuclear receptors, that also include receptors for steroid hormone, vitamin D3 and thyroid hormone act as ligand-inducible transcription factors and are characterized by the presence of two well conserved DNA- and hormone-binding domains. One of the most intriguing properties of RA is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions. We and others have shown that the t(15;17) translocation specifically associated with APL fuses an as yet unidentified gene, named PML, to the retinoic acid receptor alpha locus. The resulting PML-RAR alpha hybrid protein that retains most of the functional domains of parental proteins exhibits altered transactivating functions when compared to the wild-type receptor; however the biological significance of this property in the transforming phenotype is still obscure. PML, whose function is unknown, belongs to a novel family of nuclear proteins characterized by the presence of a Cys/His-rich motif, named a RING finger, that include RNA-binding proteins, transcription factors and oncoproteins. A dimerization domain within PML is able to mediate the formation of PML-RAR alpha homodimers that can bind to target sequences with distinct DNA binding properties if compared with RAR alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗

PubMed1995

[Considerations on the use of carbohydrate-deficient transferrin in officially recognized medial psychological examination centers].

In recent years Carbohydrate Deficient Transferrin has been introduced as a new marker to diagnose alcoholism. It has proved to have superior qualities compared to other markers like Gamma-Glutamyl-Transferase (GGT). With reference to current research the authors critically discuss the sensitivity and the specificity of CDT. The use of CDT when verifying a claim of abstinence is thought to be very low. In addition, CDT is of only limited use in the detection of above average alcohol consumption. Other questions regarding the performance of CDT require further scientific research. Therefore the authors argue that, at present, it is too early to use CDT in the context of medico-psychological examinations of drink drivers.

Alcoholism↗

PubMed1995

Selective T cell depletion with CD8-conjugated magnetic beads in the prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

The effects of a new immunomagnetic method of selectively depleting CD8+ lymphocytes from donor bone marrow were studied in 29 patients undergoing transplantation from HLA-identical sibling (n = 20) or alternative (n = 9) donors. The direct immunomagnetic depletion method consistently removed > 95% of CD8+ cells and the non-specific loss of other cell subsets was only about 15%. Recovery of CFU-GM and BFU-e was on average > 100%. The final graft contained 0.9 +/- 0.6 x 10(8)/kg nucleated cells and 1.4 +/- 2.7 x 10(5)/kg CD8+ cells. Patients also received cyclosporine starting day -1. Engraftment occurred in 28 patients (97%), including three patients who received a non-TBI conditioning regimen. One patient receiving an unrelated transplant failed to engraft. Median time to ANC > 500 x 10(6)/L was 17 (12-23) days. Four of 20 patients receiving grafts from HLA-identical siblings (20%) developed acute GVHD grade > or = II. However, five of eight patients with grafts from alternative donors (63%) had grade > or = II GVHD. Nearly all patients developed fever around day 7, accompanied by fluid overload, mild skin rash and shortness of breath. This syndrome necessitated treatment with steroids. Immunomagnetic CD8 depletion is a simple and reproducible method of selective T cell depletion. In combination with cyclosporine it appears to be effective in the prevention of severe acute GVHD in HLA-identical sibling transplants, but not in transplants from less perfectly matched donors.

Adult↗

PubMed1995

Diarrhoea in HIV-infected patients: no evidence of cytokine-mediated inflammation in jejunal mucosa.

OBJECTIVE: To determine whether a mucosal cytokine-mediated inflammatory response is involved in cryptosporidial or microsporidial diarrhoea, as well as in diarrhoea of unknown origin in HIV-infected patients. DESIGN: Prospective study. METHODS: Jejunal biopsies were obtained from HIV-infected patients with diarrhoea. Controls were HIV-infected and HIV-seronegative patients without diarrhoea. Two biopsies were homogenized immediately and two other biopsies were first cultured for 20 h. Cytokines [tumour necrosis factor (TNF), interleukin (IL)-1 beta, IL-6, IL-8, IL-10], soluble TNF receptors (sTNFR) p55 and p75, and soluble IL-2 receptor (sIL-2R) were assessed in the homogenates and in the supernatants by sandwich enzyme-linked immunosorbent or enzyme-linked binding assays. The cytokine receptors were also measured in serum. RESULTS: Six HIV-infected patients with cryptosporidiosis, six with microsporidiosis, seven with diarrhoea of unknown origin, seven without diarrhoea, and seven HIV-seronegative patients were eligible. Four patients were excluded because of the presence of other pathogens. No cytokines were detected in immediately homogenized jejunal tissue. Following culture, IL-6 and IL-8 levels were higher in HIV-infected patients with diarrhoea of unknown origin than in HIV-seronegative controls without diarrhoea, although this was not statistically significant. No differences in serum or post-culture supernatant sTNFR p55 and p75 levels existed between the HIV-infected patients with or without diarrhoea. sTNFR, IL-1 beta, IL-10 and the sIL-2R were only detected in low amounts or not at all, and were equally distributed among all patient groups. CONCLUSIONS: This study indicates that mucosal cytokine-mediated inflammatory responses do not play an important role in the pathogenesis of different types of diarrhoea in HIV-infected patients. These results do not support the use of immunomodulatory therapy in these patients.

AIDS-Related Opportunistic Infections↗

PubMed1995

Gas exchange indices--how valid are they?

OBJECTIVE: This study examined the arterial-alveolar oxygen tension difference (AaDO2), arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2) and alveolar to arterial oxygen tension ratio (PAO2/PaO2) with regard to: (i) their correlation with the calculated pulmonary shunt in critically ill patients; and (ii) the influence of the inspired oxygen fraction on these indices before, during and after general anaesthesia. DESIGN: This study comprised two sections: (i) retrospective analyses of blood gas data retrieved from the intensive care computerised database; and (ii) analyses of arterial blood gases before, during and after abdominal and orthopaedic surgery in patients subjected to various inspired fractions of oxygen. SETTING: The study was conducted at an academic hospital. PATIENTS: The first section of the study was a retrospective analysis of blood gases retrieved from a computerised database from the surgical and respiratory intensive care units. Blood gases which indicated hypoxaemia (arterial haemoglobin saturation less than 90%) were collected from patients who suffered from adult respiratory distress syndrome. The calculated pulmonary shunt was correlated with the AaDO2, PaO2/FiO2 and PAO2/PaO2. In the second section of this study, 15 patients of American Society of Anesthesiologists status 1, scheduled to undergo peripheral orthopaedic and intra-abdominal surgery, were exposed to various concentrations of inspired oxygen before, during and after general anaesthesia. At the end of a 15-minute period of exposure to a particular level of inspired oxygen (which was varied at random), arterial blood gases were analysed. A correlation was attempted between the inspired oxygen fraction and the various indices of pulmonary gas exchange. INTERVENTION: Patients were subjected to the various inspired fractions of oxygen before, during and after general anaesthesia. A radial artery cannula, inserted under local anaesthesia, allowed the researchers to collect arterial blood gas analysis. RESULTS: The correlation between the calculated pulmonary shunt and indices of gas exchange showed r = 0.35 for the AaDO2, r = 0.08 for the PaO2/FiO2 and r = 0.40 for the PAO2/PaO2. Stepwise variable selection demonstrated that the FiO2, PaCO2, PAO2 and shunt were the main components of the final models. The inspired oxygen fraction had an effect on the indices of gas exchange inasmuch as they all varied directly with the change in inspired oxygen concentration. Furthermore, the slope of this relationship was less steep during anaesthesia than in the case of values obtained before and after anaesthesia. CONCLUSIONS: The so-called non-invasive indices of pulmonary gas exchange do not correlate well with the calculated pulmonary shunt, which is regarded as the gold standard that reflects the various components of gas exchange. We speculate that the poor performance of these indices can be explained by the fact that they do not take into account the mixed venous saturation and, except for the alveolar to arterial oxygen tension ratio, ignore the effects of alveolar ventilation. The effect of the inspired oxygen fraction on these ratios makes them difficult to interpret if similar inspired oxygen fractions are not used. The effect of the FiO2 on these indices could possibly be explained by the denitrogenation and collapse of alveoli with low ventilation perfusion ratios. The change in the slope of the FiO2 and the indices that was demonstrated during anaesthesia could possibly be explained by the expected change in the mixed venous saturation that occurs during anaesthesia.

Adult↗

PubMed1994

Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees.

Interleukin 10 (IL-10) has been shown to inhibit endotoxin-induced tumor necrosis factor (TNF) production. To assess the role of TNF in the induction of IL-10 in endotoxemia, four healthy men were studied after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). In addition, 13 healthy chimpanzees were investigated after a bolus intravenous injection of Escherichia coli endotoxin (4 ng/kg), 6 animals received endotoxin only, 4 animals received a simultaneous intravenous injection of a monoclonal anti-TNF antibody, whereas 3 chimpanzees were treated with an anti-TNF F(ab')2 fragment 30 min after the administration of endotoxin. TNF induced a modest rise in IL-10 concentrations peaking after 45 min (47 +/- 32 pg/ml; p < 0.05). IL-10 peaked 2 h after injection of endotoxin (202 +/- 61 pg/ml; p < 0.005). In both anti-TNF-treated groups, the early endotoxin-induced TNF activity was completely neutralized. Simultaneous anti-TNF treatment attenuated endotoxin-induced IL-10 release (73 +/- 13 pg/ml; p < 0.01 versus endotoxin alone), whereas postponed anti-TNF treatment did not significantly affect this response (p = 0.21). These results indicate that TNF, in part, mediates the induction of IL-10 in endotoxemia, resulting in an autoregulatory feedback loop.

Adult↗

PubMed1994

Regulation of neutrophil responses by phosphotyrosine phosphatase.

By using immunofluorescent flow cytometry, we observed a profound up-regulation of CD45 on the plasma membrane of neutrophils exposed to low levels of a culture supernatant of the Gram-negative pathogen, Fusobacterium nucleatum (FN). Plasma membranes of neutrophils freshly prepared form human blood possessed little enzymatically active phosphotyrosine phosphatase. The activity of this enzyme was markedly potentiated in plasma membranes prepared from cells preexposed to the FN culture supernatant. This activity was vanadate sensitive and could be immunoprecipitated with anti-CD45 Ab. Cells preexposed to the FN culture supernatant were inhibited in their ability to release superoxide when challenged with the bacterial chemotactic factor, FMLP, but not PMA. The tyrosine kinase inhibitor, genistein, likewise inhibited FMLP but not PMA-induced superoxide release. Pretreatment of neutrophils with vanadate reversed FN-mediated inhibition of FMLP-triggered superoxide release but had no effect on genistein-mediated inhibition of FMLP-induced superoxide release. Of several proteins tyrosine phosphorylated in response to treatment of neutrophils with FMLP, Western analysis revealed one (m.w. approximately 93,000) that was lost when FMLP-stimulated cells were exposed to FN. This effect was inhibited when the cells were preexposed to vanadate. These results are consistent with the hypothesis that plasma membrane tyrosine phosphatase modulates FMLP-induced superoxide release by reversing the effects of tyrosine kinases activated in the initial phases of cell stimulation.

Cell Membrane↗

PubMed1994

The C-terminus of lipoprotein lipase is essential for biological function but contains no domain for glycosylphosphatidylinositol anchoring.

In this study we present evidence that the C-terminus of lipoprotein lipase contains no glycosylphosphatidylinositol addition signal and is therefore not a glycosylphosphatidylinositol-anchored protein. Furthermore, we present additional evidence that the C-terminus of lipoprotein lipase is essential for biological function. Flow cytometric analysis and enzyme-activity monitoring experiments revealed no pool of lipoprotein lipase releasable by phosphatidylinositol-specific phospholipase present on the membrane of COS cells transfected with the human lipoprotein lipase gene while, in contrast, a heparin-releasable pool could be demonstrated. [14C]Ethanolamine, a constituent of the glycosylphosphatidylinositol anchor, was not incorporated into lipoprotein lipase during metabolic labeling. C-terminal deletion mutants were constructed and expressed in COS cells to investigate the presence of glycosylphosphatidylinositol addition signal on the C-terminus of human lipoprotein lipase (LPL). The specific activities of the mutants M442 [des-(Leu443-Gly448)-LPL] and M437 [des-(Cys438-Gly448)-LPL] were 78% and 59%, respectively, less than the wild type, while the M432 mutant [des-(Ala433-Gly449)-LPL] was catalytically inactive. Determination of the stability of the mutants revealed a decreased stability of the M437, compared with wild-type, whereas M442 showed the same stability. Flow cytometric analysis showed sustained membrane expression for all mutants including the inactive M432 mutant. These results suggest that the C-terminus of lipoprotein lipase is essential for maintaining intact catalytic activity but is not involved in any posttranslational proteolytic processing, including cleavage of a glycosylphosphatidylinositol addition signal. We therefore conclude that membrane-binding of the lipase is not mediated by such anchoring.

Amino Acid Sequence↗

PubMed1994

Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees.

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase-alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin-antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2-antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin-induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees.

Animals↗

PubMed1994

Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells.

Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) translocation that fuses the retinoic acid receptor alpha (RAR alpha) to a novel gene product, PML. The involvement of RAR alpha is particularly intriguing in view of the efficient therapeutic effect of retinoic acid (RA) in this disease. In this report, we show that PML is specifically localized within a discrete subnuclear compartment corresponding to nuclear bodies recognized by patient autoimmune sera. In APL cells, the PML-RAR alpha hybrid displays an abnormal localization and directs RXR and other nuclear antigens into aberrant structures that are tightly bound to chromatin. This suggests that the hybrid could exert a dominant negative effect by diverting a subset of proteins from their natural sites of action. Interestingly, treatment of APL cells with RA induces a complete relocalization of each of these proteins. We propose that the beneficial role of RA in promoting myeloid differentiation in APL might be related to its ability to restore a normal subnuclear organization.

Autoantibodies↗

PubMed1994

Fractures of the odontoid process: analysis of the functional results after surgery.

Eighteen patients who sustained type II/III fractures of the odontoid process, as classified by Anderson and D'Alonzo [2], underwent anterior screw fixation, as described in detail by Böhler [4] as well as Grob and Magerl [16]. Follow-up investigations 3, 12 and in some cases up to 60 months later confirmed sufficient functional results regarding the mobility of the upper cervical spine. The passive mobility of the cervical spine was analyzed by the radiographic evaluation technique of Dvorak and co-workers [12] and Penning [26], which revealed a hypomobility of the C2-3 segment 1 year after surgery in 11 patients and a fusion of the C2-3 vertebral bodies in 2 cases. The postoperative results including the rate of complications were compared with other authors's findings and different therapy concepts (e.g., posterior C1-2 arthrodesis, halo-vest treatment).

Adolescent↗

PubMed1994

Infection prevention in severely myelosuppressed patients: a comparison between ciprofloxacin and a regimen of selective antibiotic modulation of the intestinal flora.

PURPOSE: To study whether oral ciprofloxacin would be as effective in preventing bacterial infections in severely myelosuppressed patients as selective antibiotic modulation of the gut flora with neomycin/polymyxin B sulfate/nalidixic acid (NPN). PATIENTS AND METHODS: One hundred and five patients undergoing allogeneic or autologous bone marrow transplant, or induction therapy for acute leukemia in 1988 and 1989 were studied. Patients were stratified according to the type of therapy, and randomized in a ratio of 2:1 to either oral ciprofloxacin 500 mg BID, or a combination of oral neomycin 250 mg QID, polymyxin-B 100 mg QID, and oral nalidixic acid 1,000 mg BID. Treatment began on admission and continued until the absolute granulocyte count was greater than 500/mm3 for 3 consecutive days. RESULTS: The 96 evaluable patients were evenly distributed over the 3 treatment groups; 63 patients received ciprofloxacin and 33 received NPN. Fever developed in 92% of patients on ciprofloxacin and in 97% of patients on NPN. (P = 0.66), 6.6 +/- 5.8 and 7.2 +/- 5.3 days from the start of prophylaxis, respectively. Twenty-five patients on ciprofloxacin developed 29 microbiologically documented infections, fewer than the 26 infections in the 22 patients on NPN (P = 0.02). Patients on ciprofloxacin had fewer bacteremias (33%) than did the NPN patients (55%) (P = 0.05). Gram-negative bacteremias were very rare (2 cases; no Enterobacteriaceae), but streptococcal bacteremias were frequent in both arms (27 cases). Side effects were not significantly different, but compliance with ciprofloxacin was better. CONCLUSIONS: Ciprofloxacin is at least as effective as the combination of neomycin/polymyxin/nalidixic acid in the prophylaxis of bacterial infections in myelosuppressed patients, and is better tolerated. Additional agents to prevent streptococcal infections are needed.

Adolescent↗