Surgical management and outcome of locoregional neuroblastoma: comparison of the Childrens Cancer Group and the international staging systems

Although precise anatomic staging is prognostically important in neuroblastoma, most widely employed staging systems remain incompatible. The International Neuroblastoma Staging System (INSS) was formulated to incorporate the basic elements of several systems to and define the significance of tumor resectability, anatomic "midline," and lymph node involvement. The authors sought to determine the applicability and value of the INSS compared with the classic Evans system. Between 1980 and 1992, 424 children with the diagnosis of local or regional neuroblastoma were entered in Childrens Cancer Group (CCG) clinical trials. The patients were assigned to Evans stage I, II, or III, by clinical and surgicopathologic assessment, and were treated uniformly by Group-wide therapy protocols. INSS stage 1, 2A, 2B, or 3, was applied, by retrospective analysis, to the children in the earlier studies, and by prospective evaluation of recent patients in the current studies. Survival and relapse-free survival (RFS) rates were determined and compared, based on age at diagnosis, extent of resection, and staging reassignment. All 87 Evans stage I patients were classified as INSS stage 1 and had a 92% 3-year RFS rate. Of the 144 Evans stage II patients, 65 also qualified as INSS stage 1 patients, with an 82% RFS rate. The other 79 stage II children remained in INSS stage 2A or 2B and had a 70% RFS rate (P = .10). Of the 193 Evans stage III patients, 24 were reassigned to INSS stage 1 (85% RFS rate) and 33 to stage 2A or 2B (65% survival rate; 61% RFS rate).(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of S100b in myocardium: an intrinsic inhibitor of cardiac hypertrophy

The world fauna of the order Siphonaptera is reviewed with respect to undescribed taxa, endangered species, taxonomic specialists, developmental stages, ultrastructure, taxonomic characters, host specificity, literature, fossil record, and the phylogenetic affinities of and within the order. The 15 currently recognized families are discussed with respect to their subfamilial, tribal, and generic classification. The numbers of species in these taxa are discussed and their general distribution and host preferences are briefly outlined. The current numbers of tribes, genera, and species, including invalid names, are listed.     

Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya

BACKGROUND: HIV infection is a major risk factor for pneumococcal disease in industrialised countries. Although both are common infections in sub-Saharan Africa, few studies have investigated the importance of this interaction. We have followed up a cohort of female sex-workers in Nairobi and report here on the extent of invasive pneumococcal disease. METHODS: A well-established cohort of low-class female sex-workers, based around a community clinic, was followed up from October, 1989, to September, 1992. 587 participants were HIV positive and 132 remained HIV negative. Set protocols were used to investigate common presentations. Cases were identified clinically and radiographically. Streptococcus pneumoniae and other pathogens were diagnosed by culture. FINDINGS: Seventy-nine episodes of invasive pneumococcal disease were seen in the 587 HIV-positive women compared with one episode in the 132 seronegative women (relative risk 17.8, 95% CI 2.5 to 126.5). In seropositive women the incidence rate was 42.5 per 1000 person-years and the recurrence rate was 264 per 1000 person-years. By serotyping, most recurrent events were re-infection. A wide spectrum of HIV-related pneumococcal disease was seen: only 56% of cases were pneumonia; sinusitis was seen in 30% of cases, and occult bacteraemia, a novel adult presentation, in 11%. Despite forty-two bacteraemic episodes, no deaths were attributable to Strep pneumoniae. At first presentation the mean CD4 cell count was 302/microL(SD 191) and was 171/microL (105) for recurrent episodes. During acute Strep pneumoniae infection the CD4 cell count was reversibly suppressed (mean fall in sixteen episodes, 105/microL [123]). The neutrophil response to acute infection was blunted and was correlated with CD4 count (r=0.50, 95% CI 0.29 to 0.66). Strep pneumoniae caused more disease, at an earlier stage of HIV immunosuppression, than Mycobacterium tuberculosis or non-typhi salmonellae. INTERPRETATION: Our study highlights the importance of the pneumococcus as an early but readily treatable complication of HIV infection in sub-Saharan Africa.     

Effects of photoperiod on hypothalamic and anterior pituitary tachykinins of male Siberian hamsters during development

In previous reports from our laboratory we showed that the hypothalamus and especially the anterior pituitary gland of the Siberian hamster contain very high concentrations of substance P- and neurokinin A-like immunoreactive substances, as compared with other common laboratory rodents. It was thought, therefore, that a study of the developmental changes of these two tachykinins in the hypothalamus and anterior pituitary of male Siberian hamsters would be of interest. In addition, as this species is very sensitive to changes in environmental light, these studies were carried out in animals kept under short or long daily photoperiods. The results of this investigation show that in male Siberian hamsters, photoperiod did not markedly influence the hypothalamic concentrations of substance P- and neurokinin A-like immunoreactive substances, which steadily increased from prepuberty up to 40-50 days of age. The influence of photoperiod, however, was much more marked on tachykinin levels in the anterior pituitary gland, because the developmental increase of tachykinins in this gland was significantly more evident in animals kept under short daily photoperiods than in animals under long daily exposure to light. These results are similar to those previously obtained in female Siberian hamsters, in spite of the fact that estradiol and testosterone seem to have opposite effects on anterior pituitary tachykinin concentrations. It seems, therefore, that, in addition to gonadal steroids, other factors may be important mediators of the tachykinin response to photoperiods in the anterior pituitary of the male Siberian hamster.     

Intramolecular localization of the functional units of Sepia officinalis hemocyanin by immunoelectron microscopy

The quaternary structure of Sepia officinalis hemocyanin (Hc) as studied in immunoelectron microscopy with rabbit IgGs and Fab fragments raised against functional units (FU) Soc, Sod, Soe, Sof, Sog, and Soh and fragment Soab. The architecture of immunocomplexes shows that (i) epitopes characteristic of FUs Soc and Sog and of fragment Soab are located in the two external tiers of FUs, (ii) FUs Soh and Soe or Sod are located in arches. These results were confirmed using immunocomplexes made up of Sepia Hc and IgGs or Fab fragments purified from antisera raised against FUs of Octopus vulgaris and Octopus dofleini. Frozen-hydrated immunocomplexes containing one Hc molecule and at least one FU-specific Fab fragment were observed in the electron microscope and submitted to image processing. When the Hc molecule is viewed along its 5-fold axis (i) anti-Soc Fab fragments project on a radius passing through the arch's pillar, (ii) anti-Sof Fabs project slightly out of the arches, and (iii) anti-Soh Fabs project between neighboring arches. When applied to a recent three-dimensional (3D) reconstruction volume, these results allow us to deduce the intramolecular location of five of the eight FUs. For the last three FUs limited uncertainties remain: (i) Soc can be located in two positions in the external tier of FUs; (ii) Soa and Sob can both occupy three positions in the external tiers; and (iii) because of an immunological cross-reactivity Sod may be located in the wall and Soe in the arch, or vice versa. An analysis of the quaternary structure considering the possible locations of the 80 FUs and postulating a single type of subunit shows that 80 possibilities of paths still exist for the polypeptide chain. To solve definitely these 80 possibilities only five questions remain to be answered.     

Long-term experience with controlled expansion cylinders in the AMS 700CX inflatable penile prosthesis and comparison with earlier versions of the Scott inflatable penile prosthesis

OBJECTIVEs. To determine complication and survival rates of the AMS 700CX penile prosthesis and to compare its reliability with earlier versions of the Scott inflatable penile prosthesis. METHODS: Retrospective chart review and telephone interviews were used. RESULTS: Actual 4-year survival of the AMS 700CX device was 85%, whereas earlier versions of the device had actual 4-year survival of 46% (p < 0.0001). The observed difference in prosthesis reliability could not be accounted for by differences in patient population, surgical technique, or incidence of infections. The most significant factor that contributed to improved prosthesis survival was the lack of cylinder complications (leaks and aneurysms). CONCLUSIONS: The controlled expansion cylinders of the AMS 700CX penile prosthesis are a significant advance in reliable, low-morbidity surgical therapy for impotence.     

Simultaneous expression of smooth and rough phase properties related to lipopolysaccharide in a strain of Brucella melitensis

Brucella strains exhibit either a rough (R) or a smooth (S) colonial phase identifiable by bacteriological methods. This depends on the biosynthesis and translocation to the surface in S but not in R strains, of the O-polysaccharide chain of the lipopolysaccharide (LPS) molecule. B. melitensis biovar 1 strain EP exhibited simultaneously both S and R characteristics in relation to colonial morphology, agglutination by monospecific anti-M and anti-R sera, activity of bacteriophages lytic for rough Brucella spp. (phage R/C) and for smooth B. melitensis (phage Iz). B. melitensis strain EP expressed fewer O-chains with a similar distribution of molecular weights than B. melitensis reference strain 16M by SDS-PAGE and immunoblotting, but higher amounts of R-LPS. Quantitative determination of S-LPS by a turbidimetric latex inhibition immunoassay with monoclonal antibodies confirmed the limited expression of S-LPS in strain EP. As with other gram-negative bacteria, the phenomenon could be attributed to a deficiency in one step of the biosynthetic assembly of the O-chains.     

Nonpeptide endothelin receptor antagonists. XI. Pharmacological characterization of SB 234551, a high-affinity and selective nonpeptide ETA receptor antagonist

The present study describes the pharmacological profile of ((E)-alpha-[[1-butyl-5-[2-[(2-carboxyphenyl)methoxy]-4-methoxy-phenyl ]-1H-pyrazol-4-yl]methlene]-6-methoxy-1,3-benzodioxole-5-propanoic acid) (SB 234551), a high-affinity, nonpeptide endothelin type A (ETA)-selective receptor antagonist. In human cloned ETA and endothelin type B (ETB) receptors, SB 234551 produced a concentration-dependent displacement of [125I]-endothelin-1 with Ki values of 0.13 and 500 nM, respectively. SB 234551 elicited concentration-dependent, rightward competitive shifts in the endothelin-1 concentration-response curves in isolated rat aorta and isolated human pulmonary artery (ETA receptor-mediated vascular contraction) with Kb values of 1.9 and 1.0 nM, respectively. SB 234551 antagonized ETB receptor-mediated vasoconstriction in the isolated rabbit pulmonary artery, as demonstrated by concentration-dependent, rightward shifts in the sarafotoxin S6c concentration-response curves (Kb = 555 nM). SB 234551 produced weak functional inhibition of sarafotoxin S6c-mediated endothelium-dependent relaxation (IC50 = 7 microM). SB 234551 (10 microM) had no significant effect against contraction produced by several other vasoactive agents and did not significantly influence radioligand binding to a number of diverse receptors. SB 234551 (0. 1-1.0 mg/kg i.v.) dose-dependently inhibited the pressor response to exogenous endothelin-1 in conscious rats. In vivo pharmacokinetic analysis in the rat demonstrated that SB 234551 was rapidly absorbed from the GI tract with a bioavailability of 30%. SB 234551 had a plasma half-life of 125 min and a systemic clearance of 25.0 ml/min/kg. The present study demonstrates that SB 234551 is an antagonist with high affinity for the ETA receptor, while sparing the ETB receptor. SB 234551 is a new pharmacological tool that should assist in the elucidation of the role of endothelin in pathophysiology.     

Loss of dopamine D2 receptors in Alzheimer''s disease with parkinsonism but not Parkinson''s or Alzheimer''s disease

Qualitative analyses of midfoot stabilization in triple arthrodeses utilizing bone staple versus 4.5-mm cannulated cancellous screw fixation, with and without washers, were performed in fresh cadaveric specimens. Twenty-two trials (11 matched-pair feet) were used for direct comparison. Stiffness, defined as force/displacement, was determined at each talonavicular and calcaneocuboid joint. Ultimate load failure points of each specimen were also calculated. Trial results showed no statistically significant difference in stiffness or ultimate failure between these two forms of midfoot fixation for triple arthrodeses.     

Fidelity of DNA ligation: a novel experimental approach based on the polymerisation of libraries of oligonucleotides

Complete libraries of oligonucleotides were used as substrates for Thermus thermophilus DNA ligase, on a M13mp18 ssDNA template. A 17mer primer was used to start a polymerisation process. Ladders of ligation products were analysed by gel electrophoresis. Octa-, nona- and decanucleotide libraries were compared. Nonanucleotides were optimum for polymerisation and up to 15 monomers were ligated. The fidelity of incorporation was studied by sequencing 28 clones (2268 bases) of nonanucleotide polymers, 12 monomers in length. Of the ligated monomers, 79% were the correct complementary sequence. In a total of 57 (2.5%) mispaired bases, there was a strong bias to G.T, G.A, G.G and A.G mismatches. Of the mismatches, 86% were found to be purines on the incoming oligonucleotide, of which 71% were G. There is evidence for clustering of mismatches within specific 9mers and at specific positions within these 9mers. The most frequent mismatches were at the 5'-terminus of the oligonucleotide, followed by the central position. We suggest that sequence selection was imposed by the ligase and not just by base pairing interactions. The ligase directs polymerisation in the 3' to 5' direction which we propose is linked to its role in lagging strand DNA replication.