[A 55-year-old man with abdominal pain and fever]. / 55-jähriger Patient mit abdominellen Schmerzen und Fieber.

A 55-year-old man was admitted for evaluation of chronic abdominal pain and fever. Computed tomography demonstrated a retroperitoneal inflammatory process involving the mesenteric root. Adipose tissue biopsy showed panniculitis mesenterica with granulomas. Further examinations confirmed the diagnosis of plasmocytoma type IgG kappa. Treatment with steroids (prednisolone), resulted in immediate improvement of pain and fever. Mesenteric panniculitis represents a paraneoplastic syndrome associated with non-Hodgkin lymphoma.

Kidney Failure After Occlusion of Accessory Renal Arteries in Endovascular Abdominal Aneurysm Repair.

PURPOSE: To evaluate the incidence of acute renal failure and chronic kidney disease due to occlusion of accessory renal arteries during endovascular aneurysm repair of infrarenal abdominal aortic aneurysm. MATERIAL AND METHODS: We retrospectively reviewed the course of 181 patients (mean age, 71, SD ± 9  years) who underwent EVAR of infrarenal abdominal aortic aneurysm. The renal vessel anatomy was analyzed in all pre- and postoperative CT scans. Diameter and origin of accessory renal arteries were evaluated. Renal function was determined by pre- and postoperative serum creatinine and eGFR levels. Long-term follow-up (>3 months) of patients was available in 121 cases (66.9%). Acute kidney injury and chronic kidney failure were defined according to guidelines of "Kidney Disease: Improving Global Outcomes" (KDIGO). RESULTS: In 65 of 181 patients (33.9%), 82 accessory renal arteries were identified preoperatively. In 19 of 181 patients (10.5%), one or more accessory renal arteries were covered and subsequently occluded by the implanted stent-graft device. Neither acute kidney injury (10.3% vs 12.5%; p = .785) nor chronic kidney disease (10.7% vs 15.38%; p = .452) was detected significantly more often in patients with covered accessory renal artery. The only significant predictor of acute kidney injury was the preoperative serum creatinine level (1.12 mg/dl vs. 0.98 mg/dl; p = .03). Significant predictors for chronic kidney disease were preoperative serum creatinine, eGFR, and impaired renal function (p < .001). CONCLUSION: Coverage of accessory renal artery due to stent-graft does not lead either to temporary acute kidney injury after endovascular aneurysm repair or to chronic kidney disease. LEVEL OF EVIDENCE: Level II b.

Specific immunization using keyhole limpet hemocyanin-ganglioside conjugates.

In a search for adjuvants of non-bacterial origin for immunization with ganglioside, we investigated whether chemical coupling to immune stimulatory protein could increase the immunogenicity of sialoglycosphingolipid. A novel method for the linkage of glycosphingolipids, including gangliosides, to protein was established. The procedure includes lysis of the sphingoid double bond by ozone, reduction of the ozonolysis product to the aldehyde, and coupling to amino groups, either directly by reductamination, or by conjugation via a long aliphatic chain dicarboxylic acid linker. Using this method, gangliosides Gfpt1 (IV2-Fuc-, II3NeuAc-Gg4Cer), Glac2 [II3(NeuAc)2-LacCer], and Gtet1 (II3NeuAc-Gg4Cer) were coupled to keyhole limpet hemocyanin (KLH), and the immunogenicity of the conjugates was tested. Immunization of mice with the KLH-ganglioside conjugates led in each case to the formation of IgG- and IgM antibodies that recognized the underivatized gangliosides, respectively. In contrast to this, mixtures of KLH and ganglioside proved ineffective for immunization. KLH-tumor-associated ganglioside conjugates may, therefore, be considered as possible vaccines in immune therapy of cancer.

In the search for new anticancer drugs. 27. Synthesis and comparison of anticancer activity in vivo of amino acids, carbohydrates, and carbohydrate-amino acid conjugates containing the [N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl group.

The [N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl [(2-chloroethyl)nitrosocarbamoyl, CNC] moiety containing compounds CNC-glycinamide 2d, CNC-amino acid derivatives 7a-d, and carbohydrate-CNC-amino acid conjugates 13, 18, 22, 23, 27, and 28 were synthesized and evaluated in vivo for their anticancer activities against the murine lymphocytic leukemia P388 using the National Cancer Institute (NCI) protocol. The most active compound was 2d with a 520% increase in life span (%ILS) and 6/6 survivors after 60 days. The CNC-amino acid analogs 7a-d possessed high to moderate activities with maximum %ILS values of 270, 174, 141 and 132, respectively. Among the carbohydrate-CNC-amino acid derivatives the alpha-methyl glycoside derivatives 22 and 23 were most active with maximum %ILS values of 277 and 137, respectively, followed by the hemiacetal carbohydrate analogs 13 and 18 with %ILS values of 93 and 149, respectively, and the tetra-O-acetyl derivatives 27 and 28 with %ILS of 110 and 111, respectively. Compounds 7b, 18, 23 and 28 were then tested in vivo against the murine lymphoid leukemia L1210 using the NCI protocol. In this case, the hemiacetal type carbohydrate-CNC-amino analog 18 had the highest activity with a maximum %ILS value of 477 and 4/6 survivors on day 60, followed by 7b (275% ILS), 23 (152% ILS) and 28 (106% ILS). The lipophilicities of all CNC compounds were determined by the partition coefficient using the UV method. A correlation of %ILS values with log P values indicated, in general, an increase in cytotoxicity with a decrease in hydrophilicity for the carbohydrate-CNC-amino acid conjugates 13, 18, 22, 23 and the clinical drugs streptozotocin (1e), chlorozotocin (1f), and cymerin (1g).

In the search for new anticancer drugs. XXV: Role of N-nitrosated amadori compounds derived from glucose-amino acid conjugates in cancer promotion or inhibition.

Earlier investigators found that some N-nitrosated Amadori compounds, derived from glucose and amino acid condensation reactions, exhibit mutagenic properties and theorized that these potentially carcinogenic compounds might be formed in the human digestive system. To further investigate these compounds, N-nitrosated Amadori compounds [i.e., N-(1-deoxy-D-fructos-1-yl)-L-N-nitroso-glycine (5a), -threonine (5b), -methionine (5c), -valine (5d), -phenylalanine (5e), and -tryptophan (5f)] were synthesized by modifications of known methods. Acute toxicity tests of 5a, 5b, 5c, 5d, 5e, and 5f in male Swiss mice produced the following lowest lethal limits of toxicity: 2000, 2000, 4000, 3000, 2000, and 6000 mg/kg, respectively, whereas the highest tolerated doses were 1750, 1500, 3000, 1500, and 5000 mg/kg, respectively. The 50% lethal dose (intraperitoneally) for 5b in mice was approximately 1777 mg/kg. This value is at least three times higher than that for the over-the-counter drug ibuprofen (i.e., 495 mg/kg, intraperitoneally, in mice). Compounds 5b, 5c, 5d, and 5f were evaluated in vitro by the National Cancer Institute primary antitumor screen consisting of 60 cell lines. None of the four compounds caused a significant inhibition of cell growth, even at the maximum dosage of 10(-4) M. Compounds 5a-f were tested in vivo against the lymphocytic leukemia P388, and 5b and 5f were tested against the lymphoid leukemia L1210 in CDF1 male mice following the National Cancer Institute protocol. There were no significant differences in results between the control and drug-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical appraisals of approaches for predictive designs in anticancer drugs.

The present review provides a critical appraisal of the most important areas in cancer drug research and, ultimately, in clinical oncology and therapy, with emphasis on the elucidation of possible predictive designs for the development of new anticancer drugs. These assessments encompass the well-established anticancer drugs and congeners which have been employed over the years in clinical therapy, and the more recent exploratory agents still requiring further rigorous scrutiny in the clinical environment. These areas mainly include the bioreversible redox carriers, the boron neutron capture compounds, some new mitosis-interactive agents, cell cycle modifiers, biological-response mpdifiers, oncogene inhibitors, drug-antibody conjugates, cancer cell suppression and destruction agents, antiangiogenesis and antimetastasis agents, apoptosis-promoting agents, and gene therapy and vaccines.

Re-assessment of acidic glycosphingolipids in small-cell-lung-cancer tissues and cell lines.

The occurrence of tumor-associated glycosphingolipids (GSLs) has been documented in a variety of cancer tissues (Hakomori, 1984, 1985, 1989). In the case of small-cell lung cancer (SCLC), the monosialoganglioside IV2Fuc-II3NeuAc-Gg4Cer (Fuc-GM1; short notations of gangliosides are according to Svennerholm, 1963), first described from bovine liver (Wiegandt, 1973), was found to be a unique tumor-associated GSL (Nilsson et al., 1984). It is present in up to 90% of all SCLC cases as compared with 25% frequency in non-SCLC, and no occurrence in normal lung (Brezicka et al., 1989, 1992). Thus, Fuc-GM1 may represent a suitable target antigen for immunotherapy of SCLC, and successful experiments have been performed showing tumor-cell killing by monoclonal antibodies (MAbs) against Fuc-GM1, both in vitro and, in a mouse model, in vivo (Brezicka et al., 1991). However, an effective tumor vaccination in humans would require this antigen to be expressed by the primary tumor and also by all metastases. The co-expression of Fuc-GM1 has already been reported in primary tumors and in most but not all metastases of SCLC (Hanquing et al., 1986; Nilsson et al., 1986; Brezicka et al., 1989). In view of the significance this ganglioside may have for possible immunotherapeutical approaches to SCLC and of the difficulty in obtaining a sufficient number of samples for analysis, a re-assessment of Fuc-GM1 expression was made in SCLC primary tumors and their metastases, as well as in established SCLC cell lines. In addition, the possible presence of such gangliosides, that might help to explain the selective tetanus-toxin binding of SCLC cells (Critchley et al., 1986; Heymanns et al., 1989) was investigated. Finally, the typical occurrence of sulfatide in all SCLC tissues and cell lines could be established.