Cutaneous plasmacytosis associated with lung and anal carcinomas

Cutaneous plasmacytosis is a rare disorder characterized by a benign proliferation of mature plasma cells that appears as multiple dark-brown to purplish skin lesions, often associated with polyclonal hypergammaglobulinaemia. We present the case of a 55-year-old Caucasian man who suffered from a cutaneous plasmacytosis associated with two different carcinomas. Cutaneous plasmacytosis seems to be a reactive process because most cases reported are not associated with any apparent underlying disease. Nevertheless, because few reported cases were associated with malignancies, screening of additional neoplasms would be justified.     

The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis

Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.” Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly influenced. Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model. Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis. Conclusion The vagal nerve is therefore an important modulator of the immune system. W. Kessler and T. Traeger contributed equally to this work Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany     

Tacrolimus Combined with Two Different Dosages of Sirolimus in Kidney Transplantation: Results of a Multicenter Study

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.     

The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, Bax.

The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.     

Fibrin glue in initial treatment of epistaxis in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease).

The purpose of the present study was to evaluate the haemostatic efficacy of fibrin sealant in patients with hereditary haemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease suffering epistaxis. A retrospective observational study of patients with HHT who were admitted to an emergency room for anterior or posterior epistaxis during May 2000-March 2003. A total of 24 patients were evaluated, of whom 15 were managed with foam nasal packing during May 2000-March 2002 and another nine were treated during March 2002-March 2003 with 0.3 ml fibrin sealant spray (Quixil; Omrix, Belgium). The immediate and the distant results were compared. Immediate haemostasis was achieved in all seven patients treated with fibrin glue, with good healing of bleeding sites, no secondary bleeding, no inflammation, and no plaque or crists. Twelve months of follow-up monitoring (until October 2003) of atrophic changes of nasal mucosa, bleeding frequency and intensity proved absence of atrophy of nasal mucosa and decreased bleeding frequency. In this group, the bleeding episode duration averaged 2 min 35 s since the moment of admittance. In the nasal packing group, we found local swelling, pain, and slow healing of the bleeding site with accidental atrophy of nasal mucosa and no effect on further bleeding frequency and intensity. Removal of nasal packing frequently initiates secondary bleeding. The rates of these side effects were higher in comparison with the fibrin glue group. The bleeding episode duration was also longer. In patients with HHT suffering profuse epistaxis, fibrin glue is more effective and convenient for the patients as compared with foam nasal packing. It is also safer, since it lacks the complications that usually accompany packing as swelling, atrophy of the nasal mucosa, and secondary bleeding provoked by the removal of the pack.     

Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure

Renal function was evaluated in 104 patients with severe chronic heart failure whom we treated with captopril or enalapril. Seventy patients showed no change or an improvement in renal function (group A), and 34 patients developed functional renal insufficiency (group B). Before converting-enzyme inhibition, group B patients received higher doses of furosemide (p less than 0.02) and had lower central venous pressures (p less than 0.05) than group A patients. After 1 to 3 months of converting-enzyme inhibition, an excessive reduction in left ventricular filling pressure (to less than 15 mm Hg) or mean arterial pressure (to less than 60 mm Hg) was noted in 28 of 34 (82%) patients in group B but in only 22 of 70 patients in group A (31%) (p less than 0.001). At the end of the study, drug-induced azotemia resolved after a reduction in the dosage of diuretics, despite unaltered treatment with captopril and enalapril. Hence, the deterioration of renal function after converting-enzyme inhibition in heart failure is not a toxic or immunologic reaction to therapy but results from specific hemodynamic events that can be ameliorated by sodium repletion.     

Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of newborn infants

The aim of this study was to evaluate the cerebral synthesis of eicosanoids in the asphyctic newborn and to investigate the relation between the prostanoid profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic-ischaemic encephalopathy (HIE). Levels of 6-keto-PGF _1-α, TXB₂, PGE₂ and PGF_2-α in CSF were measured in 40 full term newborns during the first day of life. Thirty of these newborns had birth asphyxia and were divided into three groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They were compared to a control group of 10 non-hypoxic newborns. Determinations of the metabolites in CSF were performed by RIA and expressed as pg/ml (mean ± SD). The CSF TXB₂ (thromboxane A₂ metabolite) in asphyxiated newborns was always higher than in the control group (28.12 ± 10.6), and related to the severity of HIE ( p = 0:005): without HIE (50.84 ± 16.4; p = 0:02), mild HIE (80.65 ± 12.64; p ± 0:01) and moderate-severe HIE (178.14 ± 20.5; p < 0:01). The CSF 6-keto-PGF _1-α (prostacyclin metabolite) in asphyxiated newborns was always higher than in the control group (80.55 ± 12.56), but indirectly related to the severity of HIE: without HIE (240.95 ± 28.12; p < 0:01), mild HIE (183.65 ± 30.1; p < 0:01) and moderate-severe HIE (140.55 ± 25.12; p < 0:01). In the moderate-severe HIE group, the increase in TXB₂ was higher than the rise in 6-keto-PGF _1-α.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.