Osteoblastoma: experience with 23 patients.

A retrospective review of 23 patients with osteoblastoma was undertaken in an attempt to answer questions concerning the aggressiveness and potential malignancy of this tumour. Demographic information confirmed that recorded in the literature. There was no suggestion of malignant potential, but, significantly, one tumour persisted, with local recurrence after 11 operations over a period of 27 years. A second tumour, a spinal lesion, occurred (still in a benign form) after a symptom-free period of 17 years. Recognition of aggressive features clinically, radiologically and histologically suggests the need for more aggressive surgical treatment, and late recurrence indicates the need for a more guarded prognosis and longer follow-up.     

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.     

Acrometageria: A spectrum of “premature aging” syndromes

A child with manifestations of acrogeria and metageria, two “premature aging” syndromes, is presented. Because of his indistinct phenotype and because the question has been previously raised as to whether these conditions are separate, we propose the designation of acrometageria to describe this phenotypic continuum. As there is much in common clinically between acrometageria and the syndrome of type III procollagen deficiency (Ehlers-Danlos type IV), it might be presumed that a similar pathogenesis for acrometageria exists. This possibility has been tested previously, without demonstrating specific quantitative or qualitative deficits, but with some indirect evidence that collagen metabolism is deranged in these patients. One such crude indicator is the elevation of urinary hyaluronic acid levels, demonstrated in our patient and also observed in the phenotypically distinct Werner and Hutchinson-Gilford premature aging syndromes. On one hand, it could be argued that this supports the concept that premature aging syndromes exist as a biological continuum. On the other hand, it is equally valid to argue that syndromes of premature aging are so described merely because they include recognizable changes of normal aging and that the demonstration of an underlying mutation in a collagen gene, for example, invalidates their study as models of accelerated normal aging. © Wiley-Liss, Inc.     

Prevention of vascular injuries in revision total hip replacement.

Iliac-vessel injury from total hip arthroplasty is associated with hemorrhagic complications and an increased death rate. The authors identified seven patients who had severe medial displacement of the acetabular prosthesis and associated vascular injury to the iliac vessels after total hip replacement. One patient had two hip replacements. Preoperative findings included a pelvic mass (three hips), pelvic pain (eight), radiologic evidence of cement in the pelvis (three) and the acetabular prosthesis in the pelvis (eight), computed tomographic evidence of cement in the pelvis and proximity of the prosthesis to the iliac vessels (four), and arteriography showing displacement or compression of the iliac vessels (seven). Operative management in all cases involved medial exposure, mobilization and repair of the iliac vessels before revision of the hip prosthesis. Postoperative complications were deep vein thrombosis (three), in spite of prophylaxis, and occlusion of a vein interposition graft (one) requiring placement of a femoral crossover graft. There were no deaths, amputations or hemorrhagic complications. The authors advocate preoperative identification of patients who have iliac-vessel involvement by their total hip prosthesis and initial medial extraperitoneal exposure and repair of these vessels before removal of the displaced acetabular prosthesis.     

In Vivo Proton Spectroscopy of Intracranial Infections and Neoplasms

The chemical characteristics of 10 neoplastic and 11 infectious brain masses were studied by in vivo ¹H magnetic resonance spectroscopy. In tumors, peak height ratios of n-acetyl-L-aspartate to choline were decreased compared to those in normal brain tissue and infectious masses (p < 0.02), but the ratios in normal brains and those with infections did not differ. N-acetyl-L-aspartate—to-creatine/phosphocreatine ratios were significantly lower in infectious masses and tumors compared to normal brain tissue (p = 0.003). However, in progressive multifocal leukoencephalopathy, N-acetyl-L-aspartate appeared relatively unchanged. Lactate was greater than choline in 9 of 11 brains with infection, 0 of 14 control brains, and 1 of 10 tumors. Lactate-to-choline ratios were significantly elevated in infectious masses compared with tumors (p < 0.01). ¹H magnetic resonance spectroscopy is promising for the noninvasive diagnosis of focal brain masses.     

Interleukin 4 receptor targeted cytotoxicity: genetic construction and in vivo immunosuppressive activity of a diphtheria toxin-related murine interleukin 4 fusion protein.

The interleukin 4 (IL 4) receptor is expressed on various cells of the immune system, including T and B lymphocytes, macrophages and mast cells. We have constructed a recombinant protein, DAB389-mIL 4, that is composed of the enzymatically active and membrane translocation domains of diphtheria toxin fused to murine IL 4. We demonstrate that this fusion toxin selectively inhibits protein synsthesis in eukaryotic cells which express the murine IL 4 receptor. The cytotoxic potency of this fusion toxin is shown to be directly proportional to the reported number of IL 4 receptors on the surface of target cells. Since the action of DAB389-mIL 4 can be blocked with either excess mIL 4 or antibody to mIL 4, we conclude that its entry into target cells is mediated through the mIL 4 receptor. A mutant form of DAB389-mIL 4, DA(197)B389-mIL 4, in which the fragment A-associated ADP-ribosyltransferase is inactive, is not cytotoxic to murine IL 4 receptor-bearing cells. Finally, we demonstrate that DAB389-mIL 4 administered subcutaneously to DBA/2 mice results in suppression of delayed-type hypersensitivity (DTH); whereas, the non-toxic DA(197)B389-mIL 4 fails to dampen the DTH response.     

Synthesis and antiviral activity of phosphonoacetic and phosphonoformic acid esters of 5-bromo-2'-deoxyuridine and related pyrimidine nucleosides and acyclonucleosides

Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl chloride (TPS) or dicyclohexylcarbodiimide (DCCI) as condensing agents, to give a range of phosphonate esters. The carboxylic ester linkage of PAA to the 5'-position of 5-bromo-2'-deoxyuridine (BUdR, 3) was achieved via the mixed anhydride formed from (diethylphosphono)acetic acid and trifluoroacetic anhydride. Phosphonoformic acid (PFA, 2) was coupled with BUdR by using the DCCI method to give the phosphonate ester. Of these compounds only phosphonate esters in the 2'-deoxyuridine series showed significant activity against herpes simplex virus types 1 and 2. The BUdR-PAA derivative and the BUdR-PFA derivative were highly active, especially the latter, which was more active than the parent nucleoside BUdR against the type 2 virus. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agents, but an intrinsic component of antiviral activity may also be involved.     

Inhibition of cytotoxicity by sulfasalazine. I. Sulfasalazine inhibits spontaneous cell-mediated cytotoxicity by peripheral blood and intestinal mononuclear cells from control and inflammatory bowel disease patients

We have studied the effects of sulfasalazine and its metabolites on cell-mediated cytotoxicity by peripheral blood and intestinal mononuclear cells from both control and inflammatory bowel disease (IBD) patients. Sulfasalazine and sulfapyridine, as well as hydrocortisone and nordihydroguaiaretic acid inhibited spontaneous cell-mediated cytotoxicity by control and IBD peripheral blood cells. Sulfasalazine and nordihydroguaiaretic acid inhibited spontaneous cell-mediated cytotoxicity by control and IBD intestinal mononuclear cells cultured for 72 h in media alone. In contrast, 5-aminosalicylate, indomethacin and benzylimidazole had no effect on cytotoxicity by any cell population. Lectin-induced, antibody-dependent and interleukin-2-induced cell-mediated cytotoxicity, as well as lymphokine-activated killing were not inhibited by the drugs: inhibitory effects in these assays were primarily upon the underlying spontaneous cell-mediated cytotoxicity. The inhibition induced by sulfasalazine, sulfapyridine and nordihydroguaiaretic acid could not be reversed by adding the lipoxygenase metabolites leukotriene B4 or 12-hydroxyeicosatetraenoic acid. These findings demonstrate that spontaneous cell-mediated cytotoxicity by control and IBD mononuclear cells can be inhibited by sulfasalazine.