Of guinea pigs and men--an unusual case of jaundice.

A 21-year-old male presented at the emergency room with jaundice, itching, dry cough, malaise and weight loss of 10 kg during the preceding four weeks. Eighteen months earlier, the patient had suffered an automobile accident leading to polytrauma. Serological markers for viral or other causes of hepatitis were absent. For suspected secondary sclerosing cholangitis, ultrasound and ERCP were performed but failed to reveal pathological findings. A liver biopsy showed cholestatic liver disease without signs of portal field-associated hepatitis. Hepato-biliary scintigraphy demonstrated hepatocellular dysfunction. The patient finally mentioned his guinea pig farm with around 50 animals, 20 of which had recently died for unknown reasons. The patient and three of his guinea pigs were subsequently tested for serological evidence of leptospirosis. IgG and IgM antibodies reacting with Leptospira interrogans were detected in the patient's serum, and all 3 guinea pigs were serologically positive for serovar Bratislava. Bacterial culture was not successful, and also PCR tests remained negative. The clinical symptoms quickly resolved after the initiation of antibiotic therapy with amoxicillin.

Role of endotoxin in the pathogenesis of critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) occurs in association with sepsis and multiple organ failure; however, little is known about the pathomechanisms of CIP and its therapy. In order to determine the parameters which interfere with development of CIP, electrophysiological investigations of peripheral nerves and biochemical measures were correlated to each other. The present study includes 20 consecutive patients in an intensive care unit developing severe sepsis or septic shock. Nerve conduction studies and electromyography were performed with occurring sepsis (day 1, 7, 14) and neurophysiological parameters were correlated with biochemical measures, especially indicators of infection and inflammation. It was found that all patients developed neurophysiological signs of axonal motor polyneuropathy. There was a significant correlation between serum concentrations of endotoxin and interleukin-2 receptors (IL2-R) and reduction of the amplitude of the compound motor action potentials. Other clinical and biochemical parameters showed no significant correlations with neurophysiological data. This finding apparently indicates that endotoxin damages nerve axons directly or indirectly, e.g. by activation of inflammatory cascades (IL2-R). Endotoxin appears to be an essential factor in the pathogenesis of CIP in sepsis, and therapeutic options neutralizing endotoxin may prevent development of CIP.

Venous thromboembolic complications with and without intermittent intraoperative and postoperative pneumatic compression in patients with glioblastoma multiforme using intraoperative magnetic resonance imaging. A retrospective study.

OBJECTIVE: To evaluate the effectiveness of intraoperative and postoperative intermittent pneumatic compression (IPC) as a method used to decrease the incidence of deep venous thrombosis (DVT), in comparison to the standard use of graduated compression stockings, low-molecular weight heparin (LMWH) and physiotherapy during the hospital stay. All patients in this study underwent intracranial surgery for glioblastoma multiforme (GBM) using intraoperative magnetic resonance imaging (MRI) guidance. PATIENTS AND METHODS: We performed a single center retrospective study of a cohort of 153 patients who underwent surgery for GBM aided by intraoperative MRI from October of 2009 to January of 2015 at the International Neuroscience Institute (INI), Hannover, Germany. Out of all patients, 75 in comparison to 78 were operated with and without the additional use of IPC, respectively. Both groups received graduated compression stockings, LMWH and physiotherapy postoperatively as a basic thromboprophylaxis. Postoperatively the patients were screened for DVT by Doppler ultrasonography of the limbs and pulmonary embolism (PE) by CT-scan of the chest. RESULTS: DVTs were found in 6 patients with IPC and in 3 patients without IPC. The incidence of developing DVTs was therefore not significantly increased with the application of IPC from 3.9% to 8% (P-value: 0.33). No statistically significant differences were found in the probability of occurrence of pulmonary embolism (PE) with a reduction from 2.6% to 1.3% (P-value: 0.59). CONCLUSION: Our results demonstrate, that the surgical intervention and the subsequent patient immobilization, as well as the thromboprophylactic techniques used have a relatively low influence on the occurrence of thromboembolic complications than we expected. Our findings might be attributed to the overall low number of these complications in a glioblastoma multiforme patient population expected to be at a high risk for coagulopathy. In other words, in order to produce statistically significant results, we would need to increase the patient cohort. By doing so we may better detect a positive therapeutic effect. Alternatively, because of the multitude of possible complex risk-factors leading to coagulopathy in a glioblastoma patient population it might be the case that IPC has little or no effect and that there is a different underlying mechanism responsible for the observed coagulopathy.

The interferon-induced Mx-homologous protein in people with symptomatic HIV-1 infection.

Twenty-six people with symptomatic HIV-1 infection were screened for the presence of interferon (IFN) alpha and IFN alpha antibodies in their sera and the presence of the IFN-induced intracellular Mx-homologous protein in their peripheral blood leukocytes. Eleven people had measurable IFN alpha levels ranging from 1 to 40 IU/ml. None of the sera tested was positive for IFN alpha binding or IFN alpha neutralizing antibodies in the assays employed. Twenty-five of the 26 people had significant levels of the Mx-homologous protein in their peripheral mononuclear cells. The Mx concentrations varied from 0.3 to 6 U/ml in the people studied. IFN alpha-positive people had significantly higher levels of the Mx homolog than IFN alpha-negative people (P less than 0.03). Furthermore, the Mx homolog content in Walter-Reed class 2 people was significantly lower than in Walter-Reed class 5/6 people (P less than 0.01). Our results suggest that the IFN system is activated in more than 90% of the people with lymphadenopathy-associated syndrome, AIDS-related complex and AIDS. Since acid-labile IFN alpha can induce the Mx homolog in vitro endogenously produced IFN alpha seems likely to be responsible for the high Mx homolog levels detected.

Modulation of cancer patients' immune responses by administration of anti-idiotypic antibodies.

Thirty patients with Dukes stage D colon carcinoma who had undergone operative removal of the primary tumor and had growing hepatic metastases each received four intradermal injections of 0.5-4 mg of alum-precipitated goat anti-idiotypic antibodies (anti-Id). The anti-Id had been produced against murine monoclonal antibody (mAb) CO17-1A, which defines a human colon carcinoma associated antigen. All patients elaborated anti-anti-Id that shared idiotopes with mAb CO17-1A, bound to tumor cells and isolated tumor antigen, and competed with the mAb for binding to tumor cells. The clinical response was monitored by ultrasonography, CT, radionuclide scanning, and serum marker assays. Six patients had partial tumor responses; five of these had received additional booster anti-Id injections along with chemotherapy. Seven patients had stabilized tumor; six had received additional anti-Id, with chemotherapy also in four. Conclusions about the clinical role of such immunization await further study, but in demonstrating a specific response to anti-Id, our results support the use of this approach in human immunotherapy against tumors or pathogens.

Molecular cloning and characterization of a German HIV-1 isolate.

The genetic diversity of HIV-1 is well documented. Except for the HIV-1 isolate LAV-1BRU, no nucleic acid sequence of a European isolate of HIV-1 has been published to date. To further investigate the extent of the genetic variability and the evolution of HIV-1, we have isolated, cloned, and subsequently sequenced HIV-1 from a German patient with AIDS-related complex. Comparative studies of the nucleic acid sequence revealed that this isolate, designated HAN2, is highly divergent from the North American and African subtypes of HIV-1 and may represent a European subtype of HIV-1. Furthermore, a full-length molecular clone was derived from this isolate which was infectious in human T-cell lines. Therefore this new isolate will be particularly useful for studies on the genetic evolution and biology of HIV-1 as well as for testing antiviral substances and for developing vaccines.

Crossreacting idiotypes of kappa-monoclonal immunoglobulins M in sera of patients with Waldenström's macroglobulinemia.

Seventeen anti-idiotypic antisera (anti-Id) were prepared against kappa-monoclonal IgM from patients with Waldenström's macroglobulinemia. Their reactivity against homologous and heterologous IgM was tested using an ELISA. Crossreacting idiotypes were only found in two out of 289 investigated antigen-antibody reactions. One anti-Id IgG crossreacted with determinants on polyclonal IgM. These rare crossreactions were observed in Waldenström's macroglobulinemia patients with and without polyneuropathy. The scarcity of common idiotypes on different monoclonal IgM does, however, not constitute a decisive argument against common or related antibody specificities of such monoclonal IgM.

The binding of different lectins on peripheral blood mononuclear cells from patients with chronic inflammatory and malignant diseases.

Peripheral blood mononuclear cells from patients with multiple myeloma, gastrointestinal tumors, and inflammatory bowel disease were analyzed for binding of various lectins. The results demonstrated that in most of the patients with multiple myeloma a significantly increased percentage of cells positive for Lotus tetragonolobus agglutinin (LTA), peanut agglutinin (PNA), soybean agglutinin (SBA), and wheat germ agglutinin (WGA), and a decreased number of Agaricus bisporus agglutinin (ABA) positive cells were present as compared to a normal control group. This could not be shown in malignant or inflammatory disorders of the gastrointestinal tract where only some patients exhibited an increased PNA and LTA binding, respectively. Patients with the systemic malignant disease differed from patients with solid localized tumors by a significantly altered number of ABA, LTA and SBA-positive peripheral blood mononuclear cells. Double fluorescence studies using monoclonal antibodies and lectins revealed that most of the cells expressing receptors for ABA had also receptors for OKT3, whereas most of the cells with receptors for LTA, PNA, SBA, and WGA were found to be positive for OKM.

Resting energy expenditure and weight loss in human immunodeficiency virus-infected patients.

Resting energy expenditure (REE) and body composition were investigated in 60 clinically stable patients with human immunodeficiency virus (HIV) infection varying with respect to immune impairment. REEs differed significantly from predicted values (> or < 10% of the Harris-Benedict [HB] equation) in 40% of patients. Seven percent of patients showed markedly increased REE (> +20% of HB prediction), whereas REE was decreased in 13% (< -10%). Increased REE was found during all clinical stages of the disease (Walter Reed [WR] 2 through 6) and was not strictly associated with the degree of immune impairment, presence of diarrhea or Kaposi's sarcoma, nutritional state, or anamnestic wasting. Twenty-seven patients were evaluated for a mean period of 319 days; 11 lost more than 5% of their initial body weight during the observation period. Weight-losing patients were normometabolic before but showed a significantly increased REE (+7% of predicted values or +8% when compared with previous measurements) during weight loss. The degree of deviation from estimated REE was strongly associated with the degree of weight loss. We summarize that increased REE is not a constant feature of HIV infection. It is not associated with clinical and laboratory parameters of immune deficiency, but may occur during weight loss. Thus increased REE represents an inadequate adaptation to malnutrition and contributes to wasting.

Cytostatic drug sensitivity test for human multiple myeloma, measuring monoclonal immunoglobulin produced by bone marrow cells in vitro.

An in vitro cytostatic drug sensitivity test for human multiple myeloma has been developed, predicting differences in sensitivity of the individual tumor to various anticancer drugs. Bone marrow preparations containing the tumor cells were incubated with cytostatic drugs and cultured for 10 days. Using an enzyme-linked immunosorbent assay we measured tumor products--monoclonal immunoglobulin and beta 2-microglobulin--in the culture supernatants. The reduction of these products in vitro due to the drugs administered was compared with the patients' further clinical course during treatment with different standard cytostatic drug regimens. We found a predictive value of more than 80% for this easily performed test.

Acute CMV-Colitis in a Patient with a History of Ulcerative Colitis.

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.

Symptomatic sulfadiazine crystalluria in AIDS patients: a report of two cases.

As the incidence of toxoplasma encephalitis (TE) in AIDS patients increases, sulfadiazine/pyrimethamine combination therapy is broadly administered. Two cases of acute and chronic renal sulfadiazine crystallization with acute renal failure and nephrolithiasis are reported. Controlled alkalinization of the urine and high fluid intake are recommended for prophylaxis of crystalluria.

Peripheral blood lymphocyte subpopulations in multiple myeloma.

Antisera raised against idiotypic determinants of myeloma proteins and macroglobulins have been used to differentiate peripheral blood lymphocytes populations from individual patients. I.D.-positive lymphocytes not resembling plasma cells have been regularly found in peripheral blood in these diseases. This lymphocyte population is heterogeneous with respect to non-tumor-specific surface markers, such as SRBC-, Fc- and C-receptors. Tumor specific idiotypic determinants will thus allow a more correct recognition of the total tumor cell compartment in these diseases.

[The therapy of gram-negative septicotoxic diseases with pentaglobin, an immunoglobulin with an elevated IgM content (a prospective, randomized clinical study)]. / Terapiia gramotritsatel'nykh septiko-toksicheskikh zabolevanii pentaglobinom--immunoglobulinom s povyshennym soderzhaniem IgM (perspektivnoe, randomizirovannoe klinicheskoe issledovanie).

The aim of this study was to assess the efficacy of pentaglobin, a polyclonal polyvalent immunoglobulin containing IgG, IgM, and IgA, in therapy of septicotoxic diseases. Fifty-five patients with sepsis were divided into 2 perspective randomized groups. Group 1 (27 patients) were infused pentaglobin containing specific antibodies to bacterial endotoxin determinant. Immunoglobulin therapy was carried out during the first 3 days after the group was selected for study. In the other group (n = 28) no immunoglobulin therapy was carried out. During 6 weeks from the beginning of the study one patient out of 27 in group 1 (4%) died because of sepsis, whereas in group 2 nine patients died out of 28 (32%) (p < 0.01). A reliably higher titer of circulating endotoxins and a lower titer of antibodies to endotoxin determinant were revealed during the first 48 hours of experiment in the serum or plasma of patients who died in the course of the follow-up period, in comparison with the survivors.