Successful treatment of multiple brain abscesses with antibiotics alone

Seven adults with multiple brain abscesses were successfully treated with antibiotic therapy alone at The George Washington University Medical Center, Washington, D.C., during 1976-1981. Fever, meningismus, and focal neurologic signs were common presenting features. No patient presented with coma or obtundation. Etiologic agents were identified in only three cases. Computerized tomographic (CT) scans were valuable in diagnosing and monitoring the response to therapy. Decrease in the size of the lesions was noted two to nine weeks after initiation of antibiotic therapy. In all patients, clinical signs of improvement preceded evidence of resolution of lesions on CT scan. These results indicate that, in carefully selected patients in whom surgical drainage is not feasible because of the anatomic location and/or multiplicity of lesions, a prolonged course of high-dose intravenous antibiotics alone can lead to a successful outcome.     

1,3-Dimethyllumazine derivatives from Limnatis nilotica

Two previously unknown lumazine derivatives, 1 and 2, have been isolated from the parasitic freshwater leech Limnatis nilotica. The structures of the compounds have been elucidated by NMR and unambiguously corroborated by chemical synthesis.     

Differential regulation of hyaluronic acid synthase isoforms in human saphenous vein smooth muscle cells: possible implications for vein graft stenosis

Autologous saphenous vein bypass grafts (SVG) are frequently compromised by neointimal thickening and subsequent atherosclerosis eventually leading to graft failure. Hyaluronic acid (HA) generated by smooth muscle cells (SMC) is thought to augment the progression of atherosclerosis. The aim of the present study was (1) to investigate HA accumulation in native and explanted arterialized SVG, (2) to identify factors that regulate HA synthase (HAS) expression and HA synthesis, and (3) to study the function of the HAS2 isoform. In native SVG, expression of all 3 HAS isoforms was detected by RT-PCR. Histochemistry revealed that native and arterialized human saphenous vein segments were characterized by marked deposition of HA in association with SMC. Interestingly, in contrast to native SVG, cyclooxygenase (COX)-2 expression by SMC and macrophages was detected only in arterialized SVG. In vitro in human venous SMC HAS isoforms were found to be differentially regulated. HAS2, HAS1, and HA synthesis were strongly induced by vasodilatory prostaglandins via Gs-coupled prostaglandin receptors. In addition, thrombin induced HAS2 via activation of PAR1 and interleukin 1beta was the only factor that induced HAS3. By small interfering RNA against HAS2, it was shown that HAS2 mediated HA synthesis is critically involved in cell cycle progression through G1/S phase and SMC proliferation. In conclusion, the present study shows that HA-rich extracellular matrix is maintained after arterialization of vein grafts and might contribute to graft failure because of its proproliferative function in venous SMC. Furthermore, COX-2-dependent prostaglandins may play a key role in the regulation of HA synthesis in arterialized vein grafts.     

Determination of the half-life of C3 in patients and its relation to the presence of C3-breakdown products and/or circulating immune complexes

Summary Measurement of complement components in serum may not accurately assess the degree of activation of the complement system. An alternative approach is the measurement of conversion products of the complement components. The relation between the presence of an increased concentration of C3-conversion products and the metabolism of C3 was investigated. In a group of patients, circulating immune complexes were also measured (Clq-binding test) to see whether the combination of those markers yielded information on the C3 metabolism. In this study it is shown that static measurements of serum C3 levels is of no value for the degree of complement activation. Measurement of C3-conversion products may indicate C3 hypercatabolism (in 8 of the 11 patients with C3-conversion products), but it does not imply depressed C3 synthesis. Detection of circulating immune complexes by the Clq-binding assay did not always indicate a C3 hypercatabolism. Of 12 SLE patients studied, in 9 of them, a C3 hypercatabolism was detected, and 5 of these patients were clinically characterized by the presence of minor disease symptoms. Overall, the results indicated that detection of circulating immune complexes and/or C3-conversion products could not be used as an absolute measure for insight into the C3 metabolism.     

Molecular structure of the octamer d(G-G-C-C-G-G-C-C): modified A-DNA.

The deoxynucleotide fragment d(GpGpCpCpGpGpCpC) was synthesized and crystallized, and its three-dimensional structure was determined by x-ray diffraction techniques to a resolution of 2.25 A. The molecule forms a right-handed double helix in which the two base pairs at either end of the molecule are in the conventional A-DNA conformation, while the central four base pairs have a modified form in which alternate residues have sugar conformations that are closer to those in B-DNA than in A-DNA. The molecules have an intermolecular contact in which the planar terminal guanine . cytosine base pair lies on the flat minor groove surface of the A-DNA helix.     

A 53-year-old man with shock and arthritis 1 month after consolidation chemotherapy for acute myeloid leukemia

Summary We recently reported that IgM antibody-related microparticles exist in some patients with idiopathic thrombocytopenic purpura (ITP) [14]. In this study, we investigated the relationship between antiphospholipid (cardiolipin and phosphatidylinositol) antibodies and microparticles in 56 ITP patients. We used an ELISA to detect anti-phospholipid antibodies. IgG antibodies against cardiolipin and phosphatidylinositol were detected in 13 and 12 patients, respectively. The titers of IgG antibodies against these phospholipids did not correlate with the platelet-associated IgG level or the platelet count. Next, we investigated the binding of anti-phospholipid antibodies to platelets and microparticles. Microparticles were obtained by incubating washed platelets with collagen plus thrombin. ITP plasma containing IgG-class anti-phospholipid antibodies showed significantly increase binding to microparticles compared with plasma without such antibodies (p<0.001). Our results suggest that anti-phospholipid antibodies could affect the function of platelet microparticles in ITP.This work was supported in part by a Research Grant for Intractable Diseases from the Ministry of Health and Welfare of Japan.     

Determination of the growth fraction in monoclonal gammopathy with the monoclonal antibody Ki-67

The monoclonal antibody Ki-67 reacts with a nuclear antigen that is present only in proliferating cells. The proportion of Ki-67 positive cells may therefore serve as a reliable measurement for the growth fraction in normal and neoplasmic cell populations. We have tested the significance of the MoAb Ki-67 in the classification of monoclonal gammopathy and compared the results with the plasma cell labelling index. In benign monoclonal gammopathy the percentage of Ki-67 positive plasma cells (median 1.6%) was significantly lower than in untreated multiple myeloma (median 9.6). Among the patients with more than 10% Ki-67 positive plasma cells there were some very short survivors. The largest growth fractions (median 41.8%) were found in patients with relapsing multiple myeloma indicating here a different growth pattern more resembling the high-grade lymphomas. A linear correlation between the proportion of Ki-67 positive plasma cells and the labelling index was not found. Determination of the plasma cell growth fraction with the monoclonal antibody Ki-67 in monoclonal gammopathy may help to discriminate benign monoclonal gammopathy from multiple myeloma and will probably identify a subgroup of multiple myeloma patients with a poor prognosis, including those with relapsing multiple myeloma.     

Mothers' reports of infant crying and soothing in a multicultural population

OBJECTIVES—To investigate the prevalence of infant crying and maternal soothing techniques in relation to ethnic origin and other sociodemographic variables.DESIGN—A questionnaire survey among mothers of 2-3 month old infants registered at six child health clinics in Amsterdam, the Netherlands.SUBJECTS—A questionnaire on sociodemographic characteristics and crying behaviour was completed for 1826 of 2180 (84%) infants invited with their parents to visit the child health clinics. A questionnaire on soothing techniques was also filled out at home for 1142 (63%) of these infants.RESULTS—Overall prevalences of "crying for three or more hours/24 hour day", "crying a lot", and "difficult to comfort" were 7.6%, 14.0%, and 10.3%, respectively. Problematic infant crying was reported by 20.3% of the mothers. Of these infants, only 14% met all three inclusion criteria. Problematic crying occurred less frequently among girls, second and later born children, Surinamese infants, and breast fed infants. Many mothers used soothing techniques that could affect their infant''s health negatively. Shaking, slapping, and putting the baby to sleep in a prone position were more common among non-Dutch (especially Turkish) mothers than among Dutch mothers. Poorly educated mothers slapped their baby more often than highly educated mothers.CONCLUSIONS—Mothers'' reports of infant crying and soothing varied sociodemographically. Much harm may be prevented by counselling parents (especially immigrants) on how and how not to respond to infant crying. Health education should start before the child''s birth, because certain soothing techniques could be fatal, even when practised for the first time.     

Force-current relationships in intraneural stimulation: role of extraneural medium and motor fibre clustering

Animal experiments and model simulations of monopolar, intrafascicular nerve stimulation are presented to study force-current relationships (recruitment curves). The conductivity of the extraneural medium is of prime importance to the resulting recruitment curves: an insulating extraneural medium generally leads to steeper curves with lower threshold currents than a well-conducting extraneural medium. Extensive statistical comparison of experimental and model results suggests the occurrence of clustering of α-motoneurons within the fascicle, manifesting itself mainly by an increased spread in threshold currents, as opposed to the situation where the fibres are distributed uniformly throughout the entire fascicle.