Supernumerary umbilical vein in a hydropic neonate with hypertrophic cardiomyopathy

The anomalies of the umbilical vessels are uncommon, with the exception of a single umbilical artery. We report a term female infant with fetal hydrops, hypertrophic cardiomyopathy, and a four-vessel umbilical cord consisting of two umbilical arteries and two umbilical veins. The presence of two veins in the umbilical cord has been attributed to persistence of both the normal left umbilical vein and the caudal part of the right umbilical vein. This fetal vascular pathology has been reported very rarely and may be associated with increased risk of congenital malformations and adverse perinatal outcome.     

An uncommon cause of neonatal respiratory distress

We describe a term infant without any features of congenital infection, who presented with respiratory distress at birth. Respiratory distress persisted despite change of antibiotics, and chest radiography showed bilateral diffuse patchy infiltrates. Congenital infections screening obtained on the 10th day of life was reported positive for syphilis. The infant was started on penicillin G and came off oxygen within five days. Although the presentation of congenital syphilis as pneumonitis in the absence of other clinical signs is unusual, in view of the re-emergence of the disease, syphilitic involvement of the lungs should be considered in any infant presenting with persistent diffuse lung disease of unknown etiology.     

L-selectin mediates neutrophil rolling in inflamed venules through sialyl LewisX-dependent and -independent recognition pathways

The glycoprotein (GP) L-selectin initiates adhesive interactions between leukocytes and endothelial cells (EC). It functions as a lymphocyte-lectin homing receptor recognizing carbohydrate determinants of the peripheral lymph node addressing on high endothelial venules. It also mediates neutrophil rolling, the earliest interaction of neutrophils with acutely inflamed venules. Neutrophil L-selectin presents sialyl-LewisX (sLe(X)) as a ligand to P- and E-selectin in vitro, and we have proposed that this is a major mechanism of L- selectin-mediated rolling in vivo. In contrast, the contribution of neutrophil L-selectin as a receptor protein recognizing one (or more) ligand(s) on inflamed EC is unclear. To address this question, an sLe(X)-negative murine pre-B cell line, L1-2, that can neither bind vascular selectins nor roll in inflamed rabbit venules, was transfected with human L-selectin cDNA. L-selectin expression in stable transfectants was sufficient to confer significant rolling in vivo. Rolling was unaffected by neuraminidase treatment but completely blocked by anti-L-selectin monoclonal antibody (MoAb) DREG-56. Thus, L- selectin can initiate leukocyte interactions with EC determinants potentially through recognition of endothelial carbohydrates. In contrast, when human neutrophils were tested, rolling was reduced, but not abolished, by MoAb DREG-56. Likewise, treatment with neuraminidase or anti-sLe(X) MoAbs decreased, but did not abrogate, neutrophil rolling, consistent with residual EC recognition via L-selectin. Combination of MoAb DREG-56 and neuraminidase resulted in almost complete loss of rolling, as did removal of glycosylated L-selectin by chymotrypsin. Together with the demonstrable rolling of L-selectin transfectants, our results support the concept of a bidirectional interaction between L-selectin bearing sLe(X) on neutrophils and activated EC in vivo. These findings also suggest that L-selectin may mediate rolling of lymphocytes that lack carbohydrate ligands for E- or P-selectin, although probably less efficiently than through bidirectional recognition.     

Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease

Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL- 1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.     

Inosine monophosphate dehydrogenase and myeloid cell maturation

In previous studies of purine ribonucleotide metabolism in the human myeloid leukemia cell line HL-60, we observed that there is a down- regulation of guanine ribonucleotide biosynthesis from the central intermediate, inosine monophosphate (IMP) and a depletion of intracellular guanosine triphosphate (GTP) and guanosine diphosphate (GDP) pools that occur during the induced maturation of these cells. We also found that inhibitors of IMP dehydrogenase, the enzyme that catalyzes the first step of guanylate synthesis from IMP, are potent inducers of HL-60 maturation. Because of these observations we specifically investigated the activity of IMP dehydrogenase in HL-60 cells and in a new inducible human myeloid leukemia cell line, RDFD2- 25, both during maintenance culture and during induced maturation of the cells. Enzyme activity was examined directly in cell extracts with a radiometric assay that measures free 3H2O formed from [2-3H] IMP during the conversion of IMP to XMP. Uninduced HL-60 and RDFD2 cells in maintenance culture were found to have high levels of IMPD activity (5.2 to 5.7 pmol IMP metabolized/10(7) cells/min) compared with normal neutrophils and monocytes that had been purified from blood (less than 1.5 pmol IMP metabolized/10(7) cells/min). However, when HL-60 and RDFD2-25 cells were induced to mature with retinoic acid (10(-6) mol/L), dimethylformamide (6 X 10(-2) mol/L), or a known IMPD inhibitor, tiazofurin (10(-6) mol/L), IMPD activity in the cells fell by 51% to 80% within three to six hours. These changes in IMPD activity preceded detectable functional and antigenic maturation of the cells by at least 12 hours and were not temporally related to changes in cellular proliferation. These findings are consistent with the concept that the regulation of myeloid cell maturation may be influenced by intracellular concentrations of guanine ribonucleotides because IMP dehydrogenase activity is known to be rate limiting for the production of these nucleotides.     

Acute cerebral infarction in monkeys: an experimental study using MR imaging

Magnetic resonance (MR) imaging was performed in five monkeys with experimentally induced acute cerebral infarction to define the MR imaging features and correlate these with computed tomographic (CT) findings, laboratory analysis, and histopathologic studies. Acute infarct (2-4 hours after embolization) was generally visible on MR images but not on CT scans. CT at 24 and 48 hours did show the infarcts. In all cases the infarct was more clearly depicted with MR imaging and was visualized as an area of high signal intensity on T2-weighted images. Spectrometric nuclear MR measurements of the postmortem cerebral tissue confirmed prolongation of both T1 and T2 values similar to that calculated from MR images. At postmortem laboratory testing, the area of infarction detected with MR imaging had decreased specific gravity and increased water content, reflecting edema.     

Palpable prostatic nodules: comparison of US and digital guidance for fine-needle aspiration biopsy

This study was undertaken to evaluate the use of transrectal sonographically guided fine-needle aspiration biopsy and to compare sonographic with digital guidance for biopsy. In 62 patients in whom prostatic carcinoma was suspected at digital rectal examination, fine-needle aspiration biopsies were performed transperineally under sonographic guidance and transrectally under digital guidance. These patients had 89 nodules, 73 of which were sampled with both techniques. Malignant cells were obtained under digital guidance in 17 of 73 nodules (23%) and under sonographic guidance in 16 (22%). An additional seven nodules, which were not seen sonographically, were sampled under digital guidance and proved to be negative. In nine other nodules that were nonpalpable and evident only with sonography, malignant cells were obtained under sonographic guidance in three. These findings indicate that sonographic guidance for fine-needle aspiration biopsy is as good as digital guidance for palpable lesions.