Syntheses of branched-chain sugars with push-pull functionality. The reaction of methyl 4,6-O-benzylidene-3(2)-deoxy-alpha-D-erythro- hexopyranosid-2(3)-ulose with carbon disulfide, alkyl iodide, and sodium hydride gave methyl 4,6-O-benzylidene-3(2)-[bis(alkylthio)methylene]-3(2)-deoxy-alpha-D- erythro-hexopyranosid-2(3)-uloses. Methyl 4,6-O-benzylidene-2-[bis(methylthio)-methylene]-2-deoxy-alpha-D- erythro-hexopyranosid-3-ulose (5) reacted with aromatic amines to give, in a rearrangement process, N-aryl-2-aryliminomethyl-4,6-O-benzylidene-2-deoxy- alpha-D-erythro-hex-1-enopy-ranosylamin-3-uloses. The reaction of 5 with hydrazine hydrate afforded 5-methylthio-(methyl 4,6-O-benzylidene-2,3-dideoxy-alpha-D-erythro-hexopyranosido)[3,2- c]pyrazole.


Structure of the complement-activating proteoglycan from the pilose antler of Cervus nippon Temminck. An anti-complementary polysaccharide, DWA-2, isolated from an unossified pilose antler of C. nippon Temminck by digestion with pronase, gel filtration, and affinity chromatography, consisted mainly of GalNAc, GlcA, IdoA, and sulfate in the molar ratios 1.0:0.6:0.3:0.8, and small proportions of Man, Gal, GlcNAc, and protein (4.5%). Methylation analysis, NMR spectroscopy, and degradation with enzymes indicated that DWA-2 contained chondroitin sulfate A-, B-, and C-like moieties. DWA-2 showed potent anti-complementary activity, and crossed immunoelectrophoresis indicated that it cleaved complement C3 in the absence of Ca2+ ion. Digestion of DWA-2 with chondroitinase ABC or ACI reduced the anti-complementary activity to a low level, but digestion with chondroitinase B reduced the activity by approximately 40% and the enzyme-resistant fraction still showed a significant activity.


The structure of the O-specific polysaccharide chain of the lipopolysaccharide of Salmonella arizonae O61. The O-specific polysaccharide was obtained by mild degradation of the Salmonella arizonae O61 lipopolysaccharide with acid. It contained 2-acetamido-2-deoxy-D-glucose, 2-acetamidino-2,6-dideoxy-L-galactose (FucAm), and 7-acetamido-3,5,7,9-tetradeoxy-5-[(R)-3-hydroxybutyramido]-D- glycero-L-galacto-nonulosonic acid (Sug). On the basis of partial acid hydrolysis with 0.1 M HCl, solvolysis with anhydrous HF in methanol, and 1H- and 13C-NMR analysis (including 1H/13C inversely correlated spectroscopy for localisation of N-acyl substituents), it was concluded that the O-specific polysaccharide had the following structure. ----3)-alpha-L-FucAm-(1----3)-alpha-D-GlcNAc-(1----8)-beta-Sug+  ++-(2---- The O-antigen of S. arizonae O61 is structurally related to that of Pseudomonas aeruginosa O12, thus explaining the known serological cross-reactivity between these micro-organisms.


Structure of the D-mannan of the pathogenic yeast, Candida stellatoidea ATCC 20408 (type II) strain, in comparison with that of C. stellatoidea ATCC 36232 (type I) strain. Acid treatment of the cell-wall D-mannas of Candida stellatoidea strains ATCC 36232 (Type I, A3 strain) and ATCC 20408 (Type II, A2 strain) gave (1----2)-linked beta-D-manno-oligosaccharides (dp 2-5), whereas treatment with alkali gave the (1----2)-linked alpha-D-mannobiose. Conventional acetolysis of the acid- and alkali-treated D-mannan of the A3 strain gave oligosaccharides consisting of (1----2)- and (1----3)-linked alpha-D-mannopyranose residues, similar to those of Candida albicans serotype B strain. Mild acetolysis of the acid- and alkali-treated D-mannan of the A2 strain gave higher oligosaccharides that were digested by the Arthrobacter GJM-1 strain exo-alpha-D-mannosidase. The results of 1H- and 13C-NMR analyses indicated this D-mannan to contain branches with the following structures: beta-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp++ +-(1----2)-alpha-D-Manp- (1----2)-D-Man, beta-D-Manp-(1----2)-beta-D-Manp-(1----2)-alpha-D-Manp -(1----2)- alpha-D-Manp-(1----2)-D-Man, and beta-D-Manp-(1----2)-beta-D-Manp-(1----2)-beta- D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp-(1- ---2)-alpha-D-Manp- (1----2)-D-Man, in common with the D-mannans of C. albicans serotype A strains.


Solution conformation and properties of the galactoglucan from Rhizobium meliloti strain YE-2(S1). The physicochemical solution properties of the galactoglucan excreted by Rhizobium meliloti strain YE-2(S1) have been investigated by capillary viscometry, potentiometric titration, isothermal mixing microcalorimetry, and circular dichroism. Potentiometric and chiro-optical data, as a function of the degree of ionisation, indicate the absence of a co-operative conformational transition. Solution properties, as a function of ionic strength and temperature, suggest that the galactoglucan adopts a disordered conformation characterised by moderate flexibility. Polyelectrolyte theory is used to fit the enthalpy of dilution data with a suitable linear charge-density parameter. Conformational calculations and chain modelling, using molecular mechanics, give an unperturbed characteristic ratio, (C infinity) of 20, which was smaller than that estimated from intrinsic-viscosity and molecular-weight data for an expanded-coil chain model.


Structures of the O chains from lipopolysaccharides of Campylobacter jejuni serotypes O:23 and O:36. Lipopolysaccharides of C. jejuni serotypes O:23 and O:36 have been shown to contain structurally variable O polysaccharide chains with repeating units of four closely-related types: ----3)-beta-D-GlcpNAc-(1----3)-alpha-D-Galp-(1----2)-6d-alpha-D-alt-H epp-(1---- , ----3)-beta-D-GlcpNAc-(1----3)-alpha-D-Galp-(1----2)-6d-3-Me-alpha-D-alt -Hepp- (1----, ----3)-beta-D-GlcpNAc-(1----3)-alpha-D-Galp-(1----2)-D-glycero-alpha-D-a lt-Hepp - (1----, and ----3)-beta-D-GlcpNAc-(1----3)-alpha-D-Galp-(1----2)-3-Me-D-glycero-alph a-D-alt - Hepp-(1----. Structural methods included 1H- and 13C-NMR spectroscopy, methylation linkage analysis, fast atom bombardment mass spectrometry of methylated glycans, and selective fragmentations by the Smith degradation and N-deacetylation-nitrous acid deamination.


Cyclic (1----2)-beta-D-glucans (cyclosophorans) produced by Agrobacterium and Rhizobium species. Neutral and acidic cyclic (1----2)-beta-D-glucans (cyclosophorans), obtained from culture filtrates and cells of Agrobacterium and Rhizobiun, are synthesised on the cell surface and then secreted. Eight cyclosophorans with dp 17-24 were isolated; all of the strains of Agrobacterium showed almost the same distribution pattern, whereas there were three other distribution patterns for the strains of Rhizobium.


Occurrence of 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid as an N-acyl substituent in the O-polysaccharide chain of the lipopolysaccharide of Vibrio anguillarum V-123. A new and highly branched amino acid was found as an N-acyl substituent of the O-polysaccharide chain obtained from the lipopolysaccharide of Vibrio anguillarum V-123 (serogroup JO-2) and evidence is presented to support the structure as 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. Acid hydrolysis of the O-polysaccharide gave the lactone of 2,4-dihydroxy-3,3,4-trimethylglutamic acid, together with 2-amino-2-deoxy-D-galacturonic acid, 2-amino-2,6-dideoxy-D-glucose (D-quinovosamine), and 4-amino-4,6-dideoxy-D-glucose (D-viosamine). Degradation of the O-polysaccharide with hydrogen fluoride yielded a fragment (H1) that was indicated by the 1H-NMR data to be 4-amino-4,6-dideoxy-D-glucose N-acetylated with 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. The configuration of the amino acid was not determined.


Structure of the O-polysaccharide chain of the lipopolysaccharide of Vibrio anguillarum V-123. The O-polysaccharide chain (PS-1), released by mild acidic treatment of the LPS of V. anguillarum V-123 (serogroup JO-2), a pathogenic bacterium of marine and estuarine fish, consists of 2-amino-2-deoxy-D-galacturonic acid, 2-amino-2,6-dideoxy-D-glucose (D-quinovosamine), and 4-amino-4,6-dideoxy-D-glucose (D-viosamine) N-acylated with 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. Strong-acid hydrolysis of PS-1 afforded alpha-GalNA-(1----4)-alpha-GalNA-(1----3)-QuiN (A1) and alpha-GalNA-(1----3)-QuiN (A2), and hydrolysis with hydrogen fluoride gave N-acetylated A1 and 4-amino-4,6-dideoxy-D-glucose N-acylated by 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. Mild treatment of PS-1 with alkali removed the N-formyl substituents and Smith degradation of the product gave alpha-QuiNAc-(1----3)-beta-VioNAcyl-(1----3)-alpha-GalNAc A-(1----3)-2,3,4- trihydroxybutanoic acid (S1) and S2 in which the carboxyl group of the GalNAcA residue was amidated. Thus, the repeating unit of the O-polysaccharide is----3)-alpha-GalNAcA(amino)-(1----4)-alpha-GalNFoA-(1----3 )- alpha-QuiNAc-(1----3)-beta-VioNAcyl-(1----in which the N-Acyl group is 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid and Fo is formyl.


The "pseudo double-helical" structure of the gel-forming capsular polysaccharide from Rhizobium trifolii. X-ray diffraction analysis of oriented fibers of the gel-forming, neutral, doubly branched, galactoserich capsular polysaccharide from Rhizobium trifolii has been used to determine and refine the molecular structure to a final R value of 0.28. The polysaccharide forms a 2-fold single helix of pitch 20.2 A, is stabilized by a series of hydrogen bonds that involve the side chains, and has the appearance of a double helix. Packing calculations reveal that the short-range ordering of these "pseudo double helices" is brought about by intermolecular hydrogen bonds that involve the side chains. Complete or partial removal of side chains will weaken the molecular association and is detrimental to the gelation process.


Structures of the oligosaccharides obtained from the core regions of the lipopolysaccharides of Bradyrhizobium japonicum 61A101c and its symbiotically defective lipopolysaccharide mutant, JS314. The only core oligosaccharide released from the lipopolysaccharide (LPS) of Bradyrhizobium japonicum 61A101c by prolonged (5 h) mild hydrolysis with acid, and the major core oligosaccharide obtained from its symbiotic and LPS-defective mutant, JS314, was the trisaccharide alpha-D-Man p-(1----4)-alpha-D-Glc p-(1----4)-2,7-anhydro-alpha-Kdof. The 2,7-anhydro-3-deoxy-alpha-D-manno-2- octulofuranosonic acid moiety was probably formed during the prolonged mild hydrolysis with acid. A disaccharide core component, also released by mild acid hydrolysis of the mutant LPS, had the structure 4-O-Me-alpha-D-Man p-(1----5)-Kdo. The Kdo residue in this disaccharide is present as the normal pyranose form and as an anhydro derivative, possibly 4,8-anhydro-3-deoxy-D-manno-2-octulosonic acid, which may have formed also during prolonged mild hydrolysis with acid. Mild acid hydrolysis of the LPS of the parent strain does not produce this disaccharide, but 4-O-Me-Man is found exclusively in the O-chain fraction released from the parent LPS. Additionally, a small amount of O-chain is found in the mutant LPS. The results imply that the O-chain is attached to the remainder of the LPS through the 4-O-Me-Man-Kdo disaccharide component of the core region.


Studies of model compounds for the analysis of ester-containing polysaccharides by the reductive-cleavage method. The four O-propionyl regioisomers of methyl tri-O-methyl-alpha-D-glucopyranoside and the 2- and 3-O-propionyl regioisomers of methyl tri-O-methyl-beta-D-glucopyranoside were subjected to reductive cleavage in the presence of Et3SiH and Me3SiOSO2CF3, BF3.Et2O, or Me3SiOSO2Me-BF3.Et2O. The O-propionyl group was stable when either Me3SiOSO2CF3 or BF3.Et2O was the catalyst, but was slowly reduced to the (1-propyl) ether when Me3SiOSO2Me-BF3.Et2O was the catalyst. Reductive cleavages catalyzed by Me3SiOSO2CF3 were complete in 6 h, those catalyzed by BF3.Et2O required at least 24 h, and those catalyzed by Me3SiOSO2Me-BF3.Et2O required 30 min or less. In the alpha-series, the rate of reductive cleavage decreased in the order 6-O-propionyl greater than 4-O-propionyl greater than 3-O-propionyl much greater than 2-O-propionyl. The reductive cleavage of beta anomers was faster than that of the corresponding alpha anomers. This effect was particularly striking for the alpha and beta anomers of the 2-O-propionyl regioisomer, as would be expected on the basis of a participation reaction.


Structure of an acidic glycan from the reference strain for Serratia marcescens serogroup O22. In addition to a neutral glycan, lipopolysaccharide extracts from the reference strain for Serratia marcescens serogroup O22 contain an acidic polymer which probably defines the serogroup and is of microcapsular origin. The polymer is doubly branched with a heptasaccharide repeating unit and a galactan backbone. By means of spectroscopic and degradative studies, the structure of the repeating unit was established as that shown. [formula: see text]


The structure of a glycerol teichoic acid-like O-specific polysaccharide of Hafnia alvei 1205. The O-specific polysaccharide of Hafnia alvei 1205 contained D-glucose, D-galactose, 2-acetamido-2-deoxy-D-glucose, 4-acetamido-4,6-dideoxy-D-glucose (Qui4NAc), glycerol, phosphate, and O-acetyl groups. On the basis of 1D and 2D shift-correlated homonuclear and 13C-1H heteronuclear NMR spectroscopy, methylation analysis, Smith degradation, and dephosphorylation with hydrofluoric acid, it was concluded that the O-antigen was a partially O-acetylated teichoic acid-like polysaccharide having the following structure: [formula: see text]


Structure of the exopolysaccharide produced by Lactococcus lactis subspecies cremoris H414 grown in a defined medium or skimmed milk. The structure of the exopolysaccharide of Lactococcus lactis subsp. cremoris H414, isolated from a defined medium or skimmed milk, was established by linkage analysis on the native polysaccharide, and by characterisation of oligosaccharide fragments, obtained by Smith degradation and partial acid hydrolysis, using methylation analysis, FABMS, EIMS, and 1H-NMR spectroscopy. The polysaccharide has the branched-pentasaccharide repeating unit: [formula: see text]


Pythium aphanidermatum: culture, cell-wall composition, and isolation and structure of antitumour storage and solubilised cell-wall (1----3),(1----6)-beta-D-glucans. Under optimal conditions for the culture of the fungus Phytium aphanidermatum, no polysaccharides were excreted into the medium. The mycelium contained up to 38% of a slightly branched, storage (1----3),(1----6)-beta-D-glucan with a MW of 20,000. The cell-wall polysaccharides of the mycelium comprised 18% of cellulose and 82% of (1----3),(1----6)-beta-D-glucans. Of the non-cellulosic glucans, approximately 33% could be solubilised by extraction with water at 121 degrees, and they had a MW of 10,000, were highly branched, and contained 6% of (1----6) linkages. Treatment of the cell wall with 0.1 M trifluoroacetic acid released approximately 50% of the non-cellulosic glucans. The acid-soluble cell-wall (1----3),-(1----6)-beta-D-glucans of lower MW (6000) were still highly branched and contained 14% of (1----6) and 8% of (1----4) linkages. The storage glucan and the hot-water-soluble cell-wall glucan exhibited strong activity against the Sarcoma 180 in CD-1 mice, whereas the acid-soluble cell-wall glucans were inactive. The hot-water-soluble cell-wall glucan was also active against the DBA/2-MC.SC-1 fibrosarcoma in DBA/2 mice.


On the solution properties of bacterial polysaccharides of the gellan family. The influence of side chains and substituents on the polyelectrolyte behaviour of aqueous solutions of polysaccharides of the gellan family has been studied. The results of conductimetric and potentiometric titrations suggest that each of these polysaccharides adopts a double-helix conformation. Deacetylation destabilises the helix of rhamsan and gellan, and optical rotation data confirm these results. The side chain in rhamsan is more flexible and is remote from the carboxylate groups, and the behavior of this polysaccharide is similar to that of gellan. Gelation of deacetylated rhamsan occurs in the presence of calcium ions. The intrinsic viscosity as a function of ionic strength depends on the structure of the polysaccharide and on the presence of acetyl groups.


Determination of the structure of the capsular antigen of Escherichia coli O8:K46:H30, using FABMS and 2D-NMR spectroscopy. The structure of the capsular antigen from Escherichia coli O8:K46:H30 was elucidated by methylation analysis and 1D and 2D 1H- and 13C-NMR spectroscopy, and by methylation analysis, 1D- and 2D-NMR spectroscopy, and FABMS of the oligosaccharide-alditol obtained after dephosphorylation of the polymer with aqueous hydrofluoric acid. The capsular polymer is of the teichoic acid type and has the following repeating unit. [Formula: see text]


The structure of the O-specific polysaccharide from Hafnia alvei strain 38 lipopolysaccharide. The O-specific polysaccharide of the lipopolysaccharide from H. alvei strain 38 has been established by NMR spectroscopy (13C and 1H) and methylation analysis to have the repeating unit-->4)-beta-D-ManpNAc-(1-->4)-alpha-D-GlcpNAc(1-->.


Taxonomic implication of the apparent undetectability of 3-deoxy-D-manno-2-octulosonate (Kdo) in lipopolysaccharides of the representatives of the family Vibrionaceae and the occurrence of Kdo 4-phosphate in their inner-core regions. After conventional hydrolysis of lipopolysaccharides (LPSs), Kdo was not detectable by the periodate-thiobarbituric acid test in those of any member of Vibrionaceae except the gems Plesiomonas, but phosphorylated Kdo was demonstrated after strong-acid hydrolysis. Dephosphorylation, periodate oxidation, and methylation analysis of LPS preparations from 7 strains selected from all genera of Vibrionaceae, except Plesiomonas, showed that the inner-core region (unlike that in enteric Gram-negative bacteria) contains only one molecule of Kdo 4-phosphate 5-substituted with heptose, a constituent of the distal part of the core region, as in enteric bacteria. The undetectability of Kdo in LPS after conventional hydrolysis and the occurrence of phosphorylated Kdo in strong-acid hydrolysates and of Kdo 4-phosphate in the inner-core region are taxonomic characteristics of the family Vibrionaceae.


GLC-MS of reduced, acetylated, and methylated (2----4)- and (2----8)-linked disaccharides of 3-deoxy-D-manno-octulopyranosonic acid (Kdo). Synthetic alpha- and beta-(2----4)- and alpha- and beta-(2----8)-linked disaccharides of 3-deoxy-D-manno-octulopyranosonic acid (Kdo), of which the synthesis of the beta-(2----4)-linked compound is described here, were used to develop a simple GLC-MS method for the determination of their anomeric configuration. The GLC and GLC-MS data for the reduced and acetylated or methylated derivatives of the above compounds indicate the alpha-linked synthetic disaccharides to be identical to those isolated from bacterial lipopolysaccharides.


Synthesis and preliminary characterisation of new esters of the bacterial polysaccharide gellan. Under the appropriate experimental conditions, ethyl, propyl, and methylprednisolon-21-yl esters of gellan can be obtained without significant degradation. At low degrees of esterification (de), depending on the ester moiety, the products are water-soluble, which allows the influence of hydrophilicity and charge density on their ability to assume an ordered conformation in dilute aqueous solution to be studied. With high de, the products were soluble only in organic solvents (e.g., methyl sulphoxide) with good film-forming capacity. The methylprednisolon-21-yl esters have been characterised in a preliminary manner in terms of drug-release kinetics.


Structure of the core oligosaccharide in the lipopolysaccharide isolated from Aeromonas salmonicida ssp. salmonicida. The core oligosaccharide isolated from the lipopolysaccharide of Aeromonas salmonicida ssp. salmonicida has been investigated by methylation analysis, NMR spectroscopy (13C and 1H), oxidation with periodate and chromium trioxide, and Smith degradation. The following structure is proposed: [Formula: see text]


Re-investigation of the structure of the capsular polysaccharide of Klebsiella K15 using bacteriophage degradation and inverse-detected NMR experiments. The structure of the capsular polysaccharide from Klebsiella K15 has been re-investigated, principally by 1D and 2D 1H- and 13C-NMR spectroscopy of the oligosaccharide-alditol obtained by depolymerisation of the polysaccharide with a viral-borne endoglycanase followed by borohydride reduction of the isolated repeating oligosaccharide. The capsular polysaccharide was shown to have the repeating unit: [Formula: see text]


Immunohistochemical analysis of lymphocyte subsets infiltrating gastric carcinoma after mitomycin C administration. The intensity of lymphoid cell infiltration and distribution of lymphocyte subsets in tumors were investigated immunohistochemically on tumor tissues obtained from 11 patients with gastric carcinoma, who had been treated with mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were compared with those obtained from 24 untreated patients as controls. In the tumor tissues from pretreated patients, the intensity of lymphoid infiltration was not significantly different from that of untreated patients. However, high-grade infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas only 8% of control patients exhibited the high-grade infiltration (P < 0.02). Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells was more frequently estimated to be more than 1 in patients pretreated with MMC, as compared to untreated controls (P < 0.02). Further, CD25+ cells in pretreated tumor tissues were more predominant than those in control tumor tissues (P < 0.05). These results suggest that MMC administration induces these alterations in lymphocyte subsets in tumor tissue in patients with gastric carcinoma.


Penetration of anti-melanoma immunotoxin into multicellular tumor spheroids and cell kill effects. In order to gain a better understanding of the interaction between immunotoxins and tumor cells at the level of three-dimensional tumor mass, we evaluated the cell kill effects of monoclonal antimelanoma-antibody/ricin-A-chain immunotoxin (ITN) on melanoma cells in multicellular tumor spheroids (MTS) as well as the penetration of ITN into MTS. For Minor melanoma cells in monolayer the ITN exerted cytotoxic effects after as little as 1 h of exposure. Increasing exposure time resulted in progressive increases in cytotoxic activity. In contrast, the cell kill effects of ITN were markedly delayed and reduced when Minor cells were in MTS. The ITN cytotoxic effects on the melanoma MTS were more than 100 fold less than those in monolayer. Patterns of ITN-induced cytotoxicities for Minor and for another melanoma cell line, DND-1A, were comparable. The native ricin A was more active against PC-10 squamous lung cancer cells than Minor cells, whereas the ITN was more cytotoxic against Minor cells than PC-10 cells, thus exhibiting selectivity. An autoradiographic study revealed time-dependent penetration of radiolabeled ITN from the surface of Minor MTS into the core. Incubation for 1 h resulted in the penetration of ITN into only the two or three outer layers of the Minor MTS, and low grain counts. Prolonged exposure resulted in inhomogeneous penetration of ITN into almost the entire melanoma MTS. Penetration of ITN into PC-10 MTS was extremely poor. The reduced cytotoxicity of ITN on melanoma cells in MTS as compared to cells grown in monolayer appears to correlate with its inhomogeneous distribution in the MTS. The delayed cytotoxicity of ITN is also consistent with its slow penetration into the core of the MTS.


Significant antitumor effect of a synthetic lipid A analogue, DT-5461, on murine syngeneic tumor models. The antitumor effect of a synthetic lipid A analogue, DT-5461, was investigated using syngeneic tumor models in mice. Intravenous injection of DT-5461 into mice transplanted with solid tumors of MethA fibrosarcoma, MH134 hepatoma, MM46 mammary carcinoma, Lewis lung carcinoma (3LL), and colon adenocarcinomas 26 and 38 resulted in significant reductions in the weight of all tumors except Colon 26, with marked hemorrhagic necrosis of tumor tissues. Efficacy was almost equal to that of an Escherichia coli-type synthetic lipid A (compound 506), and also to those of some chemotherapeutics including Adriamycin, mitomycin C, fluorouracil and cisplatin. Furthermore, DT-5461 was more effective than other immunotherapeutics, including picibanil (OK-432) and lentinan. However, its antitumor effects were inferior to those of Adriamycin or OK-432 against the malignant ascites caused by intraperitoneal inoculation with MethA or with MH134 cells; life span was not prolonged by either intraperitoneal or intravenous administration. In addition, although DT-5461 showed direct inhibitory effects on the in vitro growth of MethA or MH134, these were much weaker than those of Adriamycin. These findings clearly indicated that DT-5461 with systemic administration is a highly effective antitumor agent on solid tumors, and suggest that the antitumor effect of DT-5461 with potent necrotizing activity might derive from indirect mechanisms related to the activation of host immune systems and not to the weak direct cytotoxicity.


Active specific immunotherapy with Newcastle-disease-virus-modified autologous tumor cells following resection of liver metastases in colorectal cancer. First evaluation of clinical response of a phase II-trial. A group of 23 colorectal cancer patients were treated by a new type of active specific immunotherapy (ASI) following complete surgical resection of liver metastases (RO resection). For ASI treatment we used a vaccine consisting of 1 x 10(7) autologous, irradiated (200 Gy) metastases-derived tumor cells incubated with 32 hemagglutination units (HU) of Newcastle disease virus (NDV). The adjuvant vaccine therapy was started 2 weeks after surgery and was repeated five times at 14-days intervals followed by one boost 3 months later. The delayed-type hypersensitivity (DTH) skin reactions to the vaccine were measured as well as the DTH reactions to a challenge test of 1 x 10(7) non-virus-modified autologous tumor cells from liver metastases or 1 x 10(7) autologous normal liver cells. In addition 32 HU NDV alone and a standard antigen test (Merieux test) were applied pre- and post-vaccination. The vaccination was well tolerated. In 13 of 23 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. Nine patients (40%) experienced an increased DTH reactivity against autologous tumor cells following vaccination, while 17% or fewer showed an increased reactivity to Merieux test antigens, NDV, or normal liver cells. The increased antitumor response was not correlated to responsiveness to NDV alone, autologous liver cells, enzymes and culture medium used for vaccine preparation or standard antigens (Merieux test). After a follow-up of at least 18 months 61% of the vaccinated patients developed tumor recurrence in comparison to 87% of a matched control groups from the same institution that had been only surgically treated. The results of this phase II trial are encouraging and should stimulate further prospective randomized studies.


Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.


Tumor necrosis factor alpha modifies resistance to interferon alpha in vivo: first clinical data. Patients with Philadelphia-positive chronic-phase chronic myelogenous leukemia (CML) resistant to interferon (IFN) alpha were treated in a phase I/II study with recombinant human tumor necrosis factor alpha to overcome IFN alpha resistance. Doses of 40, 80, 120 or 160 micrograms/m2 TNF alpha were given as 2-h infusions on 5 consecutive days every 3 weeks. IFN alpha (4 x 10(6) IU/m2 s.c., daily) treatment was continued. Six patients were treated, completing 1-24 (median, 12) treatment cycles. Five of the six patients achieved partial hematological remission, while the remaining patient had to stop treatment because of WHO grade 4 thrombocytopenia following the first TNF alpha cycle. No complete hematologic remission or cytogenetic improvement was seen. Side-effects were similar to those described for both substances alone. Maximum tolerable TNF doses usually varied between 80 micrograms/m2 and 160 micrograms/m2. To examine possible pathways of TNF activity in these patients, interferon receptor status and (2'-5')-oligoadenylate synthetase levels were examined in peripheral blood mononuclear cells. Both parameters remained unchanged during TNF alpha treatment. These preliminary data point to significant clinical efficacy of additionally applied TNF alpha in IFN alpha-resistant CML patients.


Tumorigenicity of interleukin-2 (IL-2)-cDNA-transfected L1210 lymphoma and its in vivo variants is modulated by changes in IL-2 expression; potential therapeutic implications. To study parameters that affect the tumorigenicity of L1210 lymphoma we have analyzed the structure of MHC class I antigens of this tumor. In addition this tumor was transfected with interleukin-2 (IL-2) cDNA in order to determine the effects of high concentrations of IL-2 within the tumor environment. The nucleotide sequence of the class I Kd, Dd and Ld mRNAs from this tumor showed that the encoded amino acid sequence of the corresponding antigens is normal, thus suggesting that the tumorigenicity of L1210 lymphoma is not due to defective antigen presentation to tumor-specific cytotoxic T cells. In contrast, induction of IL-2 expression by cDNA transfection led to loss of tumorigenicity of the IL-2-secreting tumor cells. However, a fraction of long-term-surviving mice developed progressively growing variant tumors that showed substantial decrease or loss of IL-2 expression. These results suggest that IL-2 secretion by tumors is suicidal but, because of tumor heterogeneity, IL-2-loss-variant tumors may arise that are able to escape the immune defenses of the host. The observed consistent loss of IL-2 expression in variant tumors implies that specific targeting of large quantities of IL-2 to tumor cells may be a valuable approach to immunotherapy of cancer. In addition we find that under specific gamma ray irradiation IL-2-secreting tumor cells lose their ability to multiply yet continue to secrete IL-2 at levels equivalent to those secreted by unirradiated cells. Such IL-2-secreting irradiated tumor cells were found to be superior immunogens in comparison to the irradiated parental tumor cells, suggesting their use as tumor vaccines.


Blocked ricin-conjugated T cell immunotoxins: effect of anti-CD6-blocked ricin on normal T cell function. The biological properties of an immunotoxin composed of an anti-CD6 monoclonal antibody conjugated to whole ricin, which had been modified so that the galactose-binding sites of the B chain were blocked ("blocked ricin"), were examined. Treatment of peripheral blood lymphocytes with anti-CD6-blocked ricin for a 24-h period prevented T cell proliferation induced by phytohemagglutinin in a dose-dependent manner with concentrations causing 50% inhibition (IC50) ranging from 5 pM to 30 pM. In contrast, treatment with either blocked ricin alone or with a control immunotoxin prepared with a B-cell-lineage-restricted monoclonal antibody gave IC50 values of approximately 2 nM. Although shortening the duration of the anti-CD6-blocked ricin treatment to as little as 3 h had little significant effect on the observed inhibition, T cell viability experiments demonstrated that the magnitude of immunotoxin-induced killing after a given time period is significantly higher when the target cells become activated. Thus, from the initial concentration of cells treated with anti-CD6-blocked ricin placed in culture, 40%-45% viable cells remained after 2 days yet only 3%-9% remained if phorbol ester and Ca2+ ionophore were added; activation of T cells after mock treatment using blocked ricin plus nonconjugated anti-CD6 demonstrated that this effect was not the result of activation alone. The toxicity of anti-CD6-blocked ricin was also measured by inhibition of PHA-induced clonogenic growth of normal T cells. Continuous treatment of the cells using anti-CD6-blocked ricin at 0.1 nM resulted in a surviving fraction of about 3.5 x 10(-3); when immunotoxin treatment was for 24 h or less, the surviving fraction was only about 10(-1). As an indication of the unique specificity of anti-CD6-blocked ricin, immunotoxin pretreatment of potential responder cells prevented the generation of allogeneic cytolytic T lymphocytes in mixed lymphocyte cultures yet had little effect on the generation of interleukin-2-induced lymphokine-activated killer cell activity. We conclude that anti-CD6-blocked ricin demonstrates a cellular specificity and potency that make it a highly promising anti-T cell reagent.


Quantitative autoradiographic evaluation of the influence of protein dose on monoclonal antibody distribution in human ovarian adenocarcinoma xenografts. We studied the effect of monoclonal antibody protein dose on the uniformity of radioiodinated antibody distribution within tumor masses using quantitative autoradiography. Groups (n = 11-13/group) of athymic nude mice with subcutaneous HTB77 human ovarian carcinoma xenografts were injected intraperitoneally with an 125I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4 using a high or a low protein dose (500 micrograms or 5 micrograms). At 6 days post-injection the macroscopic and microscopic intratumoral biodistribution of radiolabeled antibody was determined. The degree of heterogeneity of the labeled antibody distribution within each tumor was quantified and expressed as the coefficient of variation (CV) of the activity levels in serial histological sections. Tumors from mice given the 500-micrograms protein doses had substantially lower CV values, 0.327 +/- 0.027, than did tumors from animals given 5-micrograms protein doses, 0.458 +/- 0.041, (P = 0.0078), indicating that the higher protein dose resulted in more homogeneous distribution of radioactivity in tumors than did the lower dose. While the percentage of the injected dose reaching the tumor was comparable between groups, injecting the higher dose of protein resulted in significantly lower tumor to non-tumor uptake ratios than those obtained for the lower protein dose. These data indicate, in this system, that to achieve more uniform intratumoral antibody (and radiation for radioimmunotherapy) delivery, a relatively high protein dose must be administered. However, to obtain this increased uniformity, a substantial drop in tumor/background uptake ratios was seen. Quantitative autoradiographic evaluation of human tumor xenografts is a useful method to assess the intratumoral distribution of antibodies.


Antitumour activity of a sterically blocked ricin immunotoxin on a human colorectal adenocarcinoma grafted subcutaneously in nude mice. We prepared a ricin-antibody conjugate, lacking the ability to bind the galactosidic residues of Sepharose 6B, a so-called blocked immunotoxin. The monoclonal antibody AR-3 was cross-linked to ricin through a thioether bond. Further studies showed that the immunoconjugate suppressed the tumour growth of HT-29 cells in intraperitoneally grafted nude mice, without showing any undesirable ricin toxicity. In this work, to demonstrate the therapeutic activity of the AR-3-ricin conjugate injected into mice bearing subcutaneous tumour, we first evalauted its pharmacokinetic behaviour and biodistribution. The behaviour of the immunoconjugate injected intravenously was almost intermediate between that of the antibody and ricin. Moreover, when the immunotoxin was intravenously administered to nude mice bearing subcutaneous tumour, no therapeutic effects appeared, in accordance with the relatively low permeability of the immunotoxin from the blood to the skin. In contrast, peritumoral treatment produced a strong reduction of the neoplastic nodules without substantial regrowth of the malignant cells. This result was also achieved when the immunotoxin treatment was performed on a well-established tumour. This finding was strictly related to the specifcity of the immunoconjugate, since the analogous treatment with an irrelevant immunotoxin showed therapeutic failure.


Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-alpha 2a and interleukin-2. Immunological parameters were evaluated in patients treated with cytokine-mediated immunotherapy (CMI) consisting of low doses of recombinant human interferon alpha 2a (rIFN alpha) and recombinant human interleukin-2 (rIL-2) administered either concomitantly or sequentially by subcutaneous self-injections in an outpatient setting. Twenty-six patients with hematological malignancies and 2 metastatic melanoma patients in a progressive stage were enrolled in this clinical trial. Of the 26 patients, 24 were at a stage of minimal residual disease, including 14 patients who had received autologous bone marrow transplantation (ABMT) 2-5 months previously, 7 chronic myelogenous leukemia (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1 mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK-sensitive (K562) target cells was assessed before, during and after CMI, either in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2 activation (induced activity). Spontaneous killing activity was low prior to treatment, but increased upon termination of treatment in 10/15 evaluated cycels. rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8 patients after one and two cycles, respectively, of sequential treatment, as well as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of concomitant treatment. Activation of the T cell mitogenic response was demonstrated in 6/9 patients after concomitant CMI, while no such effect was observed throughout a sequential treatment in lymphoma and leukemia patients after ABMT. Although a direct correlation between immune stimulation and the in vivo antitumor response cannot yet be determined, our clinical observations support a beneficial therapeutic effect in a substantial number of patients. These results indicated that the ambulatory CMI protocol of rIL-2 and rIFN alpha could stimulate the host defense immune system and may be helpful in mediating the in vivo antitumor response in patients with minimal residual disease.


A new 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for testing macrophage cytotoxicity to L1210 and its drug-resistant cell lines in vitro. Activated by interferon gamma (IFN gamma)(50 U/ml) and lipopolysaccharide (50 ng/ml), mouse peritoneal macrophages were cocultured with the L1210 parental cell line (L1210/PRT) and its Adriamycin-, cisplatin-resistant cell lines (L1210/ADM, L1210/CDDP) for 24 h at effector: target (E:T) ratios of 10:1, 5:1 and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT)-cleavage assay, a new improved indirect MTT assay, and the colony-formation assay were used to quantify macrophage-mediated suppression of these non-adherent tumour targets. The results showed that the macrophages can produce formazan at a high level, which can interfere with the final results of a direct MTT assay. The new indirect MTT assay can avoid such interference because the effectors are separated from the targets before the assay is performed, so the real viability of the targets is reflected. An indirect MTT assay, as developed in this study, could be better than the direct assay for examining the suppressive effect of activated macrophages on non-adherent tumour cells in vitro. This study also revealed that all the L1210 cell lines can be suppressed significantly by the macrophages at E:T ratios of 10:1 and 5:1 while the two drug-resistant cell lines have lower survival rates at an E:T ratio of 10:1, indicating that they are more susceptible than their parental cell line.


T lymphocyte killing by a xanthine-oxidase-containing immunotoxin. We report on the preparation of an immunotoxin consisting of xanthine oxidase, a free-radical-producing enzyme, covalently linked to an anti-CD3 monoclonal antibody. The immunotoxin retained both enzymic and immunological properties and its toxicity to target cells (a) was greater than that of the free enzyme, (b) was proportional to the enzyme concentration, and (c) was reduced either in the absence of hypoxanthine or by an excess of free anti-CD3 monoclonal antibody. The cytotoxicity and selectivity of the hypoxanthine/conjugated xanthine oxidase system were potentiated by the addition of chelated iron and by washing away the unbound immunotoxin prior to the addition of substrate. The same system was not toxic to bone marrow progenitor cells. A possible use of this immunotoxin for the ex vivo purging of organs to be transplanted from T lymphocytes, to avoid the graft-versus-host reaction, is suggested.


[The antianginal effects of a new delayed-release formulation of diltiazem in patients with stable angina pectoris: its evaluation by the ergometry test and dynamic electrocardiogram]. The antianginal efficacy and duration of action of slow-release (SR) diltiazem were evaluated in 12 patients with stable angina. Patients underwent maximal symptom limited bicycle exercise testing and 24-hour Holter monitoring at the end of 1-week placebo run-in phase and after 1-month therapy with either placebo or SR-diltiazem (120 mgs bid) using a placebo controlled, double-blind, randomized cross-over trial. No concomitant antianginal therapy, except sublingual nitroglycerin, was allowed during the trial. Exercise testing was performed 3 and 12 hours after drug administration. Blood samples were obtained for the determination of diltiazem plasma concentrations. After diltiazem administration, peak exercise duration increased significantly in comparison both with placebo and the run-in phase: from 292 +/- 48 to 378 +/- 113 s at 3 hours and from 286 +/- 59 to 366 +/- 109 s 12 hours after drug administration. Similarly, ST depression time increased from 240 +/- 59 to 374 +/- 123 s at 3 hours and from 231 +/- 57 to 332 +/- 123 s 12 hours after diltiazem. No significant changes of heart rate, blood pressure and double product were detected. Diltiazem plasma concentrations averaged, respectively, 175 +/- 86 pg/ml and 109 +/- 43 pg/ml 3 and 12 hours after its administration. No correlation was found between plasma concentrations and antianginal effects of diltiazem. At 24 hours Holter monitoring, SR-diltiazem induced a significant decrease of mean heart rate with a reduction in the number and duration of ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)


[Aortic stenosis and coronary pathology. Their implications for the transvalvular gradient]. To assess the incidence of coronary artery disease in patients with valvular aortic stenosis and its implication on peak systolic valvular gradient, 31 consecutive patients who underwent cardiac catheterization were examined. Associated significant coronary artery disease (> 50% reduction in luminal diameter evaluated in proximal segments and right dominant circulation) was present in 54.8% of patients. There was no difference in the distribution of risk factors among patients with and without significant luminal narrowings. The prevalence of coronary artery disease was found not to be significantly correlated with age (p = 0.276). There was no relationship between typical angina pectoris and the presence of coronary artery disease (p = 0.063). Fourty-seven percent of cases resulted free of chest pain. Ejection fraction was found to be significantly lower in patients with coronary artery disease (45 +/- 14.2%) than in patients without coronary artery disease (65.1 +/- 3.9%; p = 0.03) and a reverse relationship was observed between the presence of coronary artery disease and peak systolic valvular gradient (p = 0.006) which, in turn, correlated significantly with ejection fraction (r = 0.68; p = 0.023). These data demonstrate that the value of peak systolic valvular gradient, as the only index for the evaluation of the severity of aortic stenosis, is greatly limited in patients with associated coronary artery disease. Moreover, confirming the guidelines of the American College of Cardiology and of the American Heart Association task force, these data also stress the necessity of performing coronary angiography regardless angina pectoris is present or not.


[Angioplasty in total occlusion of the coronary arteries: the importance of the angiographic variables]. Total coronary occlusions can be treated by coronary angioplasty with a lower success rate when compared to the angioplasty success rate of stenoses. To evaluate factors associated with successful re-opening of total coronary occlusion we evaluated 128 occlusions attempted in 120 patients. We analyzed clinical and angiographic variables. Successful re-opening was obtained in 65% of total occlusions attempted; 1 patient (0.8%) had to undergo emergency coronary artery bypass surgery. Only the morphological characteristics of the occlusions were predictive of success. When total occlusions had a tapered morphology, success was achieved in 87% of the attempts versus 50% of success without tapered morphology (p < 0.001). The success, when the occlusion was associated with the presence of bridging collaterals, was very low (present: 30% success; absent: 71% success, p < 0.005). Success for occlusions longer than 1.5 cm was lower when compared to shorter occlusions (61% vs 78%; p < 0.005). The type of occlusion (absolute, functional), the presence of a branch originating at the level of the occlusion, the duration of the occlusion, the artery and its segment were not predictive of success. Multivariate analysis showed that tapered morphology was the only variable associated with successful re-opening of a total occlusion (87% probability of success when present). We conclude that it is possible to re-open a total coronary occlusion with low complication rate and high primary success rate when careful care is applied with particular attention paid to the morphology of the occlusion.


[Increased serum levels of IgA and C4 in atherosclerosis: the absence of a correlation with the arteriographic picture]. We have previously shown that an increase in serum IgA and C4 is often detectable in presence of diffuse atherosclerotic disease. The present study was performed to verify such results in a different and larger sample of subjects, and to ascertain whether the above immunologic variables are correlated with the severity of atherosclerotic disease. Seventy-three atherosclerotic subjects with at least 1 significant (> 75%) stenosis in a major arterial branch were selected according to the reports of arterial panangiographies performed previously. Among them, 36 subjects (24 men and 12 women, mean age 63 +/- 7 years) were singled out, who matched by age and sex 36 control subjects (mean age 63 +/- 7 years). In all of these subjects the following serum immunologic and lipid variables were measured: IgG, IgA, IgM, IgE, C3, C4, total cholesterol, HDL-cholesterol and triglycerides. With respect to the controls, the 36 matched atherosclerotic subjects had higher levels of IgA (263.0 +/- 119.8 vs 334.3 +/- 130.5 mg/dl; p = 0.0126), C4 (25.7 +/- 5.8 vs 30.4 +/- 9.1 mg/dl; p = 0.0297) and triglycerides (153.1 +/- 77.3 vs 209.7 +/- 141.3; p = 0.0500). No correlation was found between the number of arterial stenoses (range 1-8, mean 2.9 +/- 1.5) and any of the immunologic or lipid parameters in all the 73 atherosclerotic subjects. Only the daily cigarette consumption was correlated with the disease extension (tau = 0.1984; p = 0.0392).(ABSTRACT TRUNCATED AT 250 WORDS)


[The coronary angioplasty of oversized vessels by the hugging-balloon and single guiding-catheter technic: a case report]. A case is described of percutaneous coronary angioplasty performed on an oversized right coronary artery (> 7 mm), using the hugging balloon technique. The procedure and the equipment utilized are described.


Distribution and size of particles after dynamic angioplasty in cadaveric arteries with the Kensey catheter system: a comparison with clinical experience. The distribution and size of atheromatous debris after angioplasty with the Kensey catheter was determined after recanalization of 18 segments of human cadaveric superficial femoral arteries (SFA). The debris produced was studied cytologically and measured semiquantitatively. Nearly 80% of all particles ranged from 5 to 15 microns, approximately the size of red blood cells. More than 20% of all particles exceeded this size and 2% were larger than 100 microns. The use of the Kensey catheter dynamic angioplasty system in the lower extremities contains the risk of embolic complications because more than 20% of all particles are larger than human blood cells. Seven patients with occlusion and 3 with stenoses of the SFA were treated with the Kensey catheter system. Recanalization was successful in all and in 1 case, small emboli in the anterior tibial artery were observed. There was a 50% restenosis/reocclusion rate between 2 weeks and 10 months.


Percutaneous transluminal angioplasty for occlusion of the subclavian artery: short- and long-term results. Percutaneous transluminal angioplasty was performed in 8 symptomatic patients with proximal occlusion of the left subclavian artery. Technical and short-term clinical success was achieved in 7 cases. Nonoccluding embolization to the distal subclavian artery and stenosis of the brachial artery after a combined femoral/brachial approach occurred as complications in 2 patients. Three patients are asymptomatic with a patent subclavian artery 25, 28, and 37 months after angioplasty. Reobstructions in 4 patients occurring after 8, 12, and 16 months were retreated by angioplasty (3 patients) and stent implantation (1 patient with a second restenosis) with good technical and clinical success. Long-term patency was less than 50%, but successful retreatment is feasible. Therefore, we consider percutaneous transluminal angioplasty a reasonable therapeutic option in patients who are not surgical candidates.


Percutaneous transluminal angioplasty of tibial arteries for limb salvage. Percutaneous transluminal balloon angioplasty (PTA) was performed in 17 tibial arteries with an average cross-sectional area stenosis of 92% (range 75-99%) in 13 patients (14 limbs) for limb salvage. In 4 of 14 lower extremities, PTA of femoropopliteal arteries was also performed. Technical success with 50% or less residual stenosis was achieved in all 17 tibial vessels. At approximately 2 months after PTA, clinical improvement had occurred in 10 of 14 limbs; no patient was made worse. Most recent follow-up (mean 19 months, range 8-34 months) revealed continued satisfactory clinical success with no further vascular intervention in 9 of these 10 limbs (one patient died). Short segmental stenoses, residual stenoses less than 40% following PTA, and absence of diabetes or gangrene appear to be predictors of favorable clinical outcomes. Our results suggest that PTA of focal tibial stenosis is an effective and safe treatment modality in properly selected patients and that wider use of PTA may be justified.


Percutaneous transcatheter ethanol sclerotherapy of postoperative pelvic lymphoceles. Although percutaneous procedures have been used for the treatment of lymphoceles, transcatheter sclerosing therapy has not been widely applied. We present the results of transcatheter sclerotherapy of lymphoceles with 96% absolute ethanol in 7 patients who had developed lymphocele after pelvic lymphadenectomy for uterine cancer. Seven of the eight lymphoceles (88%) completely disappeared after treatment. The duration of catheter drainage ranged from 4 to 21 days. Although one lymphocele did not resolve completely, it did not require surgery as the patient's symptoms resolved.


Strecker stent in stenotic hemodialysis Brescia-Cimino arteriovenous fistulas. Flexible tantalum stents (Strecker) were used as an adjunct to percutaneous transluminal angioplasty (PTA) in the treatment of stenotic arterial or venous limbs of Brescia-Cimino hemodialysis fistulas. The diagnostic procedure was performed using retrograde fistulography. After PTA with unsatisfactory results, stents were placed in 5 patients with significant residual stenoses and poor fistula function. Within the mean follow-up period of 6.4 months (range 3-10 months) all fistulas were functioning. We conclude that Strecker stent is useful in the treatment of stenotic hemodialysis arteriovenous fistulas as an adjunct to PTA.


Pulse-spray pharmacomechanical thrombolysis. The synergistic potential of combining pharmacologic and mechanical methods of thrombolysis has recently been recognized. Pulse-spray pharmacomechanical thrombolysis is one such method, which in our experience has markedly increased the efficiency and acceptability of thrombolysis. With this technique, dialysis grafts usually require only 20-35 min for thrombolysis; bypass grafts or native arteries usually require 60-150 min. The entire procedure is accomplished in one session within the angiography suite, including the supplemental transluminal angioplasty, atherectomy, or stenting that is usually also necessary. Clear understanding of the principle of the method and meticulous attention to technical details is essential for maximal speed, safety, and efficacy.


Thrombosis of the popliteal vein.

Thrombosis of the popliteal vein. Among 3,307 consecutive patients (3,556 legs) with deep venous thrombosis, 54 (1.5%) showed an isolated thrombus of the popliteal vein on phlebography. The majority of those had a history of "effort" or long lasting flexion during air or bus travel. Forty-four percent suffered from pulmonary embolism as the first sign of deep venous thrombosis. Functional phlebography demonstrated the primary site of thrombosis at folds forming in the vein wall at flexion. In order to further elucidate the pathogenetic mechanism, 158 popliteal veins were examined phlebographically in different functional states revealing age-related characteristic wall patterns of rings and folds in flexion causing transient impairment of flow. Complementary morphological studies of 120 popliteal veins during autopsy showed a transverse rippling of the vein wall caused by intimal fibrosis and partial atrophy of the media corresponding to the phlebographic findings. It is concluded that microtrauma during effort in combination with impaired venous backflow and fibrotic transformation of the venous wall can lead to thrombus formation in the popliteal vein.


Angiographic findings in a patient with primary antiphospholipid syndrome: case report. A case of antiphospholipid syndrome (APPS) is presented. A 33-year-old female presented with a right hemispheric stroke secondary to thrombosis of the middle cerebral artery. Shortly thereafter, she developed thrombosis of the right brachial artery. Despite thrombolytic therapy, progressive occlusion of this artery occurred as demonstrated by a follow-up angiogram. The patient had a history of multiple recurrent spontaneous abortions. Lupus anticoagulant, anticardiolipin antibodies, and VDRL were positive on two different occasions. The angiographic findings of multiple and progressive arterial thrombosis in young women should alert the angiographer to the possibility of APPS.


Effect of monensin on the neuronal ultrastructure and endocytic pathway of macromolecules in cultured brain neurons. 1. The endocytic pathway of horseradish peroxidase (HRP) was investigated in the perikarya of cultured neurons by electron microscopy and enzyme cytochemistry. The tracer was observed in endocytic pits and vesicles, endosomes, multivesicular bodies, and lysosomes. It took approximate 15 min for the transfer of HRP from the exterior of the cell to the lysosomes. 2. Monensin induced distension of the Golgi apparatus and formation of intracellular vacuoles. When neurons were incubated with both monensin and HRP for 30 to 120 min, the number of HRP-labeled endosomes was greater than that in the monensin-free group, whereas the reverse was seen for HRP-positive lysosomes. The formation of HRP-positive lysosomes in monensin-treated cells was blocked by 47 to 79%. 3. These results indicate that the intracellular transport of the endocytosed macromolecule is pH dependent. It is also possible that the export of lysosomal enzymes is inhibited by monensin, resulting in an accumulation of the endosomes and a reduction of the lysosomes.


Hypoplastic superficial femoral artery associated with bilateral persistent sciatic arteries: a diagnostic pitfall. A patient with unsuspected bilateral persistent sciatic arteries (PSAs) underwent angiography following a gunshot wound to the right thigh. A hypoplastic superficial femoral artery associated with this rare vascular anomaly was misdiagnosed as being traumatically occluded. Pitfalls in the diagnosis of PSA as well as the embryology, clinical features, and complications are discussed.


Choline acetyltransferase expression studied with an oligonucleotide probe. 1. The localization of choline acetyltransferase messenger RNA has been studied using a digoxigenin-tailed complementary oligodeoxynucleotide probe for in situ hybridization. 2. Putative cholinergic cells of the rat and ferret spinal cord and the ferret retina were labeled. 3. This technique affords superior resolution compared to radioactively labeled probes, with apparently equal sensitivity.


Modified Tru-Cut needle with exchangeable blunt stylet for safe puncture: technical note. A modified Tru-Cut needle has been developed to safely bypass interposed vital structures during large-bore biopsies of solid lesions in various regions of the body. The needle allows blunt advancement in critical locations and facilitates accurate pin-point advancement when needed. The needle performed as designed in computed tomography (CT)-guided biopsies of 31 solid lesions.


Dissolution of multiple biliary duct stones using methyl tert-butyl ether (MTBE): experience in two cases. Methyl tert-butyl-ether (MTBE) was successfully used for stone dissolution in 2 patients with multiple bile duct cholesterol stones. The presence of a biliary-enteric anastomosis precluded the endoscopic approach. Because of leakage of MTBE into the bowel, dissolution time ranged from 7.5 to 36 h. No significant complications other than mild nausea were encountered. No recurrence of stone formation has been found at a follow-up varying from 9 to 12 months.


A topography and ultrastructural characterization of in vivo 5,7-dihydroxytryptamine-labeled serotonin-containing neurons in the central nervous system of Aplysia californica. 1. Several weeks after administration of 5,7-dihydroxytryptamine (5,7-DHT) to Aplysia, a dark pigmentation appears in serotonin-containing neurons, and this pigmentation allows visual identification of serotonergic neurons but does not appear to alter their physiology. 2. We have determined the distribution of labeled nerve cell bodies in the various ganglia of Aplysia and have characterized the pigment containing structures in both control and labeled neurons. 3. All neurons in this preparation, whether or not they utilize serotonin as a transmitter, contain pigment granules, and three types of pigment granules can be distinguished. After 5,7-DHT a new type of granule appears in serotonergic neurons, probably reflecting lysosomes that have accumulated serotonergic synaptic vesicles that contain the oxidized 5,7-DHT. 4. It remains unclear why this substance does not cause neurotoxicity in mollusks as it does in mammalian preparations.


Contrast injection around mandril wire of an Accustick system using an extension tubing: technical note. We describe a technique for injecting contrast material around a mandril wire of an Accustick access system through the outer 6 French sheath of this system, thus identifying the position of the wire. This is accomplished by using an extension tubing.


[Pneumocystis carinii today--40 years later]. Forty years ago Czech scientists, J. Vanĕk and O. Jírovec, diagnosed Pneumocystis carinii as the agent of interstitial plasmocytic pneumonia in weak infants. At present it is the most frequent pulmonary pathogenic organism in patients suffering from AIDS. In the submitted paper the author summarizes experience and recent findings on the aetiopathogenesis, pathology, clinical picture, diagnosis, treatment and prevention of pneumocystis pneumonia.


Isoprenylation and carboxylmethylation in small GTP-binding proteins of pheochromocytoma (PC-12) cells. 1. A group of 21 to 24-kDa proteins of pheochromocytoma (PC-12) cells was found in blot overlay assays to bind specifically [alpha-32P]GTP. Binding was inhibited by GTP analogues but not by ATP. Such small GTP-binding proteins were found in the cytosolic and in the particulate fraction of the cells, but they were unevenly distributed: about 75% of the small GTP-binding proteins were localized within the particulate fraction of the cells. Separation of these proteins by two-dimensional gel electrophoresis revealed the existence of seven distinct [alpha-32P]GTP-binding proteins. 2. Targeting of the small GTP-binding proteins to the particulate fraction of PC-12 cells requires modification by isoprenoids, since depleting the cells of the isoprenoid precursor mevalonic acid (MVA) by the use of lovastatin resulted in a 50% decrease in membrane-bound small GTP-binding proteins, with a proportionate increase in the cytosolic form. This blocking effect of lovastatin was reversed by exogenously added MVA. 3. In addition, metabolic labeling of PC-12 cells with [3H]MVA revealed incorporation of [3H]MVA metabolites into the cluster of 21 to 24-kDa proteins in a form typical of isoprenoids; the label was not removed from the proteins by hydroxylamine, and labeling was enhanced in cells incubated with lovastatin. The latter effect reflects a decrease in the isotopic dilution of the exogenously added [3H]MVA, as the addition of exogenous MVA reversed the effect of lovastatin on [3H]MVA-metabolite incorporation into the 21 to 24-kDa proteins. 4. Additional experiments demonstrated that isoprenylation is required not only for membrane association of small GTP-binding proteins, but also for their further modification by a methylation enzyme. This was evident in experiments in which the cells were metabolically labeled with [methyl-3H]methionine, a methylation precursor. The group of 21 to 24-kDa proteins was labeled with a methyl-3H group in a form typical of C-terminal-cysteinyl carboxylmethyl esters. Their methylation was blocked by the methylation inhibitors methylthioadenosine (MTA), 3-deazadenosine and homocysteine thiolactone as well as by lovastatin. MVA reversed the lovastatin block of methylation. 5. Two-dimensional gel analysis of the [3H]methylated proteins detected seven methylated small GTP-binding proteins that correspond to the isoprenylated proteins. Levels of the small GTP-binding proteins as well as isoprenylation and methylation were reduced by cycloheximide. 6. Distribution of the methylated proteins between particulate and cytosolic fractions was found to be similar to that of the small GTP-binding proteins (i.e., a 4:1 ratio).(ABSTRACT TRUNCATED AT 400 WORDS)


[Smokeless tobacco--also a danger to us?]. As a result of the decline in the prevalence of smoking in Western countries another form of tobacco addiction is developing in the shape of moist snuffs from which nicotine is released in the mouth. The addiction which develops is serious, as most people who use this form of tobacco belong to young or very young age groups. The highest prevalence is at present in Sweden and the United States, in western European countries this drug addiction is not as frequent. The authors discuss the impact on health, forms and types of moist snuff and of advertisements focused on young age groups. It is important to become familiar with these data and facts and focus attention on prevention.


[Pneumocystis carinii infection after kidney transplantation]. The authors demonstrate on the example of two patients after transplantation of the kidney with pneumocystis pneumonia their experience with this disease. Predisposing factors include prolonged immunosuppression, protein and energy malnutrition, chronic inflammations and large doses of methylprednisolone. In the clinical picture dominated acute dyspnoea with hypoxaemia and non-productive cough. In one patient the X-ray picture was quite atypical. The prognosis of the disease is poor, both patients died.


[Determination of antithrombin III in situ in the skin of patients with allergic arteriolitis]. The authors assessed antithrombin III in patients with allergic arteriolitis. Positive expression of antithrombin was assessed on endothelia, thrombi and infiltrate cells in approximately 2/3 of patients of the examined group (n = 23). The authors assume that expression of antithrombin III reflects inhibited hemocoagulation in the affected vessels as well as inhibition of leucocyte proteases in the above disease.


Percutaneous hepaticoneojejunostomy and choledochocholedochal reanastomosis using metallic stents: technical note. A new, nonsurgical approach to biliary duct reconstruction in two high-operative risk patients is presented. The first patient with an obstructed hepaticojejunostomy underwent such reconstruction by placement of Wallstent, which remained patent 9 months until death from recurrent tumor. The second patient with an inadvertently ligated common bile duct underwent a combined percutaneous transhepatic-retrograde endoscopic reconstruction with placement of a Gianturco-Rösch (GR) stent. Because of occlusion by granulation tissue 5 months later, a new GR stent covered with a silicone membrane was placed within the initial stent. Nine months after the second GR stent placement there is no evidence of obstruction.


[A case of recurrent alimentary lead poisoning]. The authors describe a case of lead poisoning in a family (father, mother, son, daughter). The condition was at first diagnosed as acute hepatic porphyria. The correct diagnosis was made on the basis of increased urinary excretion of delta-aminolevulinic acid and coproporphyrin and on the basis of the revealed reversibly inhibited activity of delta-aminolevulinic acid dehydratase in red blood cells. The source of intoxication was the use of red lead pigment instead of dried red pepper.


[The effect of chloroquine on lymphocytic HLA-A and B antigens]. The author investigated the effect of 20%, 15%, 10%, 5%, 2.5%, 1.25% chloroquine on HLA-A,B antigens on lymphocytes and on the reaction HLA-A,B antigen-antibody. HLA-A,B antigens are not released by chloroquine from the lymphocyte surface and their expressivity does not change, as was revealed by examination of the micro-lymphocytotoxic and absorption test. Higher concentrations of chloroquine cause poly-reactivity of lymphocytes. A 20%, 15% and sometimes also 10% and 5% of chloroquine solution block the reaction HLA-A, B antigen--HLA antibodies. The reason for this is the destructive action of chloroquine on rabbit complement.


[Study on the interaction between hypertension, smoking and the disorder of lipids metabolism in the coronary artery disease]. The correlations of the coronary artery disease (CAD) and hypertension, smoking and/or the levels of lipoproteins and apolipoproteins, were studied in 100 patients with CAD diagnosed by coronary arteriography and 141 non-CAD controls. The findings are: 1. There are: significant positive dose-response relationships between the degrees of CAD and the levels of diastolic pressure, cumulative smoking consumptions, the levels of high-density lipoprotein subclasses and apolipoproteins A1 and/or B. 2. The degrees of CAD in patients with the hypertension and smoking at same time were more serious than those with only a single risk factor. It's suggested that there are some synergy between hypertension and smoking in the occurrence of CAD. The synergic mechanism may be related to lipids metabolism.


[Studies on the serotyping and pyocintyping of Pseudomonas aeruginosa]. Pseudomonas aeruginosa (118 strains) from Xian were typed by 12 groups O-serum and revised pyocin typing method Results indicated that VI, I, III were major serotypes, VI type were mainly from trauma infected, I type mainly from respiration system infected. Pyocintype were mainly I and UT types. Pyocintype I were mainly 1/c and 1/x subtypes. 85.7% of 1/c subtypes were serotype VI, 84.4% of 1/x subtypes were serotype I.


[A study on EDTA antigens for detection of IgG antibodies to Legionella pneumophila]. The EDTA and Sonicate antigens used in ELISA for detection of IgG antibodies to Legionella Pneumophila serogroups 1-6 and Tatlock was evaluated. Sensitivity and specificity of EDTA antigens were compared with Sonicate antigens in three groups of subjects. In two serum samples from healthy employees, the Lp1 antibody titers with EDTA and Sonicate antigens were less than or equal to 1:160. Testing seven samples from patients indicated that four samples reacted with titers of 1:1280-2560 to Lp1 with EDTA and Sonicate antigens. But in another three samples, the antibody titers to Lp1 with EDTA antigen were lower 1-3 dilution than Sonicate antigen. One of the lowest titer to EDTA was 1:320 that was interpreted as positive. In all of the seven samples, the antibody titers to Lp4 and Tatlock raised to 1:640-2560 with sonicate antigens and significantly higher than the titers with EDTA antigens (1:320-640). The comparison between the EDTA and Sonicate antigens showed that when the antibody titer with EDTA antigens greater than or equal to 1:320 was regarded as a positive mark the sensitivity of EDTA antigens was similar to Sonicate antigens and the specificity was better than Sonicate antigens. Comparison of EDTA antigen was simple. It is worth to further study.


[Asymptomatic hepatitis B virus infection among the elderly]. The hepatitis B virus (HBV) infection usually occurs during infancy and children. To elucidate how the infection changes during the elderly life, 2233 residents were surveyed and among them 440 individuals with the age of 60-96 years were centered for analysis. The infection in the elderly was decreasing. HBsAg prevalence (5.0%) and titer (3.5 +/- 2.3) were getting lower, nearly all HBeAg seroconverted to anti-HBe, and the infection might be cleared at last. However, the HBV antibody prevalence steadily maintained, implying frequent HBV exposure and antibody responses during aging in the endemic area. Among them no fresh HBsAg were detected at one year follow-up, but antibodies developed in 10.8% of 65 individuals without HBV markers initially, and more, in 79 with single anti-HBs or anti-HBc 6.3% developed another antibody in a year. Therefore, the elderly population might be in a hypo-infection and dynamic hyperimmune status of the hepatitis B virus.


[Serological study about the infection of hepatitis B in Xiyang County, Shanxi Province]. Authors examined HBsAg, anti-HBs and anti-HBc of 471 people in Xiyang, Shanxi. The positive rate is 10.19%, 34.61% and 19.11% respectively. The total infection rate of HBV is 52.65%. It indicates that Xiyang county is highly infectious area of HB. The age distribution of positive rate of HBsAg, anti-HBs, and the infection rate of HBV present special model: i.e. goes up along with age's growing, up to 30 years old, it gets the high peak. After 30 years old, the positive rate of HBsAg is going down along with the age's growing, the positive rate of anti-HBs and the infection rate of HBV go down a little. The group of 50 years old has a high peak again. The positive rate of HBsAg of peasant is remarkable higher than cadre's. The infection rate of HBV of peasant is the highest, it is 59.55%. The infection rate of HBV of the people who work in food units is lowest, because they are examined regularly. The infection of man and woman is same.


[Cause analysis of measles incidence in National Diseases Surveillance System in 1990]. This paper described the time and areas distribution of 875 measles cases in DSP in 1990 and discussed relationship between vaccination and measles cases. Through studying cases in several points with high morbidity, the authors found that there was no high immunization coverage. It must have been the first chance of measles incidence. Further more the immunization technics and cold chain were found unqualified, which were thought to be the second chance.


[Epidemic investigation of genital mycoplasma hominis infection in women]. The genital mycoplasma hominis infection in women was investigated at Xiaguan district, Nanjin in June, 1990. Leucorrheas from 722 women were tested with ELISA for the antigen of M. hominis. The prevalences of genital M. hominis were not statistically different among age and occupation groups. Women having pregnancy more than three times had a significantly higher infection rate, it is suggested that induced abortion might provide chances of the infection. The prevalence was significantly different among groups of various contraceptive means, it is lower in the group of contraceptive condom and higher in the group of intrauterine device.


[Study of the effects of air pollution on human health in Beijing]. 3000 habitants from different polluted areas of Beijing were examined for their states of health in both the summer and the winter in 1989, and 7000 questionnaires were filled. Meanwhile, the data of air pollution surveillance during 1980 and 1988 were collected and analysed. The air pollutants in the areas have been identified. The results of the study showed that the effects of air pollution on human health in urban were more severely than that in suburb and rural area; the complaints of respiratory system were correlative with the level of pollution in the areas; and the index method is useful in the studies of the effects of multi-factor pollution of human health.


[Trend analysis of causes of death among the population in Shandong Province from 1970 to 1974 and from 1981 to 1989]. This report showed the general mortality and changes of mortality distribution among the population in Shandong province in the early 1970S and in 1980S, through data analysis of causes of death in the Province from 1970 to 1974 and from 1981 to 1989. In the past 20 years, the mortality in respiratory diseases increased by 19.21%, ranking the first among the leading causes of death; the mortality in malignant tumors and cerebrovascular diseases increased by +7.15% and 75.31% respectively, rising from the third and fourth to the second and third leading causes of death, the mortality in heart diseases changed little, remaining in the fourth leading cause of death; the mortality in infectious diseases decreased by 78.22%, dropping from the second place in the early 1970S to the eighth place.


[Influence of smoking on cholesterol concentrations in serum lipo-protein of healthy subjects]. Sixty hundred and nineteen-seven smokers and 841 non-smokers among healthy male workers of 40-60 years of age were comparatively observed. Their housing environment and working conditions were similar. The results showed that smoking had remarkable influence on the cholesterol concentration in the serum lipo-protein of healthy subjects. The levels of HDL-C HDL2-C, HDL3-C and HDL2-C/HDL3-C of the smoking group were obviously lower than those of the non-smoking group, while the levels of LDL-C, VLDL-C and LDL-C/HDL-C of the smoking group were obviously higher than those of the non-smoking group. Moreover, these indices were significantly associated with the smoking amount, smoking duration, depth of inhalation. Smoking was an important dangerous factor for lowering levels of HDL-C, HDL2-C, HDL 3-C, HDL2-C/HDL3-C and raising levels of LDL-C, VLDL-C, LDL-C/HDL-C. The relative risk (RR) of the two factors were estimated to be 1.09-5.77 and 2.37-3.57 respectively. The levels of the 7 indices such as HDL-C of passive smokers were identical with those of light smokers. This showed that passive smoking also had marked influence on cholesterol concentrations in serum lipoprotein.


Empyema in children: a review of 52 cases. A prospective study was undertaken to assess the clinical pattern, management and outcome in children admitted with empyema at Harare Hospital. Fifty-two children were seen and followed up during the three-year period, 1984-1987. All patients were managed with intrapleural drain and antibiotics. Two needed decortication. The predominant pathogen isolated from the pleural cavity was Staphylococcus aureus. All survived and on follow up only one child was found to have persistent radiological abnormality and poor exercise tolerance. Early intrapleural drainage and appropriate antibiotics should be the mainstay of treatment for empyema for the majority of children in Zimbabwe.


Pattern of HIV-infection in Hurungwe district, Mashonaland West, Zimbabwe. After the first case of HIV-infection had been diagnosed in 1986 in a Northern district of Zimbabwe, a local hospital based surveillance system, was introduced. In order to monitor the spread of the epidemic in the district, residence, age, sex and clinical presentation of all newly diagnosed HIV-patients were recorded. After three years, the data were compiled and analysed with the following results. Altogether 887 symptomatic HIV-patients (0.5 pc of the district population) were diagnosed. The most common HIV-associated signs and symptoms were PGL (47 pc), chest infection (29 pc), herpes zoster (24 pc) and chronic STDs (15 pc). The female-to-male ratio in adults was 1.4. The average age on diagnosis in women was 26.0 +/- 6.7 years and in men 30.7 +/- 8.6 years. The three years' cumulative incidence of HIV-cases was 27.2/1,000 in the urban area and 3/1,000 in the rural areas of the district.


Bacterial contamination of food and household stored drinking water in a farmworker community in Zimbabwe. Food and water samples, collected from the homes of farmworkers with children less than five years old, were cultured for Escherichia coli (which was used as an indicator of faecal contamination) and bacterial enteric pathogens. Sixteen percent of the food samples and 41 pc of the household stored water samples had E.coli. Ten percent of the foods had high E.coli counts greater than 10(4) counts per ml or g of food. Most of the foods were stored for more than 12 hours. Bacterial enteric pathogens were isolated in low percentages in foods and water except Aeromonas which was very common in household stored water. The majority of the faecally contaminated water samples had low E.coli counts (less than 20 E.coli/100 ml) and 61 pc of the water was stored for less than 12 hours. There was no relationship between faecal contamination of the water and period of storage in the home. Household stored water had a higher percentage of samples contaminated with E.coli than the tap water which was used to fill the storage vessels. Household stored drinking water is a major route of transmission of Aeromonas in the rural community which was studied.


Neurocysticercosis: experience with diagnosis by ELISA serology and computerised tomography in Zimbabwe. Over a three-year period, 646 sera from 630 patients with signs and symptoms compatible with neurocysticercosis were investigated for antibodies to cysticercal antigens using an ELISA test. Overall, 12 pc specimens were positive. The sensitivity of the ELISA, when compared with a limited number of computerised tomography investigations, was over 70 pc. False negative serology was associated with HIV infection in some patients. The positive predictive value was 87 pc and the negative predictive value was 85 pc when patients with active infection, potentially amenable to chemotherapy, were considered. The specificity, determined from serological tests of patients with a variety of trematode, cestode and other infections, was over 90 pc. Three of 11 patients with intestinal taeniasis, and each of two patients with hydatid disease were seropositive. The results suggest the value of ELISA serology as a more cost-effective diagnostic method for all patients with suspected cysticercosis.


Penetrating abdominal spear injuries.

Penetrating abdominal spear injuries. Eight cases of penetrating abdominal spear injuries are presented. The type and size of the spearhead as well as its direction and severity of the impact were reflected in the degree of visceral damage. At laparotomy, retro-peritoneal haematoma (RPH) was a constant finding. Morbi-mortality was associated with early haemorrhage or later septic complications. Manipulation of intra abdominal embedded spears may require unusual surgical procedures, and no attempt to extract the weapon should be made before emergency laparotomy is carried out. Prompt first aid and hospital referral, resuscitation and facilities for the treatment and care of the critically ill patient, were important factors influencing the outcome of these cases.


Neonatal septicaemia in Calabar, Nigeria. In a twelve-month prospective study of 132 neonates suspected of having septicaemia in the Special Care Babies Unit (SCBU) of the University of Calabar Teaching Hospital (UCTH), Calabar, 79 were confirmed by positive blood cultures. Forty (50.6 pc) of these were preterm infants. The incidence was 19.3 per 1,000 hospital live births, while the mortality rate was 30.3 pc. The main predisposing factors were birth asphyxia, birth outside hospital, prolonged rupture of membranes, prolonged labour and poor water supply in hospital. The predominant pathogens were coliform organism and Staphylococcus aureus. The antibiotic sensitivity pattern of the pathogens suggest the use of gentamicin as a sole agent in the initial treatment of septicaemia while awaiting culture results. In view of the role of inadequate antenatal care, poor water supply and unhygienic delivery practices in the aetiology of newborn septicaemia, it is suggested that improved antenatal care, water supply and childbirth practices will reduce the incidence of septicaemia.


Metastatic clostridial myonecrosis associated with intra-uterine clostridial infection: a report of three cases. Three cases of metastatic Clostridial myonecrosis are reported, two following spontaneous and one following criminal abortion. This particular combination has not been reported before. The two survivors were managed by hysterectomy and disarticulation of the leg through the hip. The patient who died did so before surgery could be undertaken. The literature on gas gangrene infections of the uterus and metastatic Clostridial myonecrosis is reviewed and guidelines for management are discussed.


Volvulus of the sigmoid colon in paediatric patients: report of two cases. Two cases of volvulus of the sigmoid colon in paediatric patients are presented. The condition is rare in childhood. The diagnosis was established at laparotomy in the first case while the second case was diagnosed because of heightened awareness. The clinical features of the disease are essentially as in adults.


Abnormal syndrome of iliac osteomyelitis presenting as acute appendicitis. A case of right iliac osteomyelitis initially misdiagnosed and treated as acute appendicitis is reported. Deep-seated right lower quadrant pain persisted and a gluteal abscess appeared in the immediate post-operative period. The gluteal abscess was incised and it continued to discharge pus until appropriate diagnosis and treatment was instituted. Pain due to iliac osteomyelitis is deep-seated and may radiate to the thighs or lumbar region. Compression and distraction of the pelvis elicits pain in the affected ilium.


The changing age ecology of measles and its implications on measles control. In the City of Gweru measles vaccination was commenced in 1971. With the advent of the Expanded Programme on Immunisation in 1981-82, measles vaccination coverage was increased, reaching over 80 pc in 1985 and after. Despite this vaccination effort measles morbidity rates have remained high and epidemics continue to occur periodically. It is argued that the shift of the disease from young age groups to older children, coupled with the fact that there are more vaccinees amongst cases with the disease, will mean that transmission will continue uninterrupted. Possible reasons for persistent transmission in older children are explored. It is concluded that measles revaccination is required to interrupt measles transmission.


Parental history of hypertension in Zimbabwe and cardiovascular reactivity to psychological experimental stress. Thirty (16 male and 14 female) black subjects with a parental history of hypertension (FH) were matched in sex and age with 30 subjects without family history of hypertension (NFH). These two subgroups of black Zimbabweans were matched in number, sex and age and compared to FH and NFH subgroups of healthy, young white subjects. The relationship between parental history of hypertension and cardiovascular reactivity to alpha- and beta-adrenergic stressors was estimated by using cold pressure and mental stressor tests respectively. Black-white differences in cardiovascular reactivity were found. Blacks at risk of getting hypertension showed greater vascular response to the cold pressor, which produces an alpha-adrenergic increase of vascular resistance, compared with the respective whites with parental history of hypertension who showed exaggerated reactivity to mental stressor, a beta-adrenergic activator that enhances cardiovascular reactivity via increases in cardiac output.


Factual knowledge about AIDS and dating practices among high school students from selected schools. Following various educational strategies by governmental and non-governmental organisations to educate youths and school teachers about HIV infection and prevention, this KABP survey was one attempt to evaluate the results. The study sample of 478 high school students was drawn from four randomly selected schools in Mashonaland and Matabeleland including high and low density, government and mission co-educational schools. The sample was randomly selected and stratified to represent sex and grade level. The KABP self administered questionnaire was used. The paper analyses the relationship between the knowledge and dating patterns. Generally, respondents demonstrated a 50pc to 80pc accuracy of factual knowledge. Of the 66pc Forms I through IV pupils who dated, 30pc preferred only sexually involved relationships and a small number considered the possibility of HIV/AIDS infection. A theoretically based tripartite coalition involving the school, the family health care services for education, guidance and support to promote responsible behaviour throughout childhood was suggested.


Socio-democratic characteristics of women presenting with abortion--a hospital based study. To determine socio-demographic characteristics and clinical features of women presenting with abortion, and to define factors associated with complications of abortion. A prospective descriptive study. Women in Gynaecology casualty department at Harare Central Hospital, Harare, Zimbabwe. 307 women with features of complete or incomplete abortion were interviewed during February to June 1991. They were randomly selected and represented 53pc of all women with the problem. Three quarters of the women were married and lived with their spouses. In 23.1pc this was a first pregnancy. Over a quarter of the women who were on the pill claimed to have fallen pregnant whilst on the pill, mainly because of poor compliance. One hundred and twenty-two were not on the pill but in only 16pc it was intended to fall pregnant. In nearly 30pc the pregnancy was not wanted but only 2.3pc admitted to having induced the abortion. Sepsis was present in 25.6pc and they tended to be younger, not presently married and have an unplanned pregnancy. Although there was some evidence of trauma in 6.2pc, it was not possible from the study to assess the percentage of abortion likely to have been induced. Contraceptive usage is generally low and cultural and traditional factors may play a role, but expanded sex education programmes and continued contraceptive counselling need reinforcing before attempts are made to review the legal issues regarding termination.


Normal pulmonary function in Botswana.

Normal pulmonary function in Botswana. Forced vital capacity, forced expiratory volume in one second and peak expiratory flow rate were measured in 125 adult Batswana who were without evidence of pulmonary disease. Regression co-efficients suitable for the calculation of normal values for these parameters are presented. Results are similar to those in other Negroid populations but lower than in Caucasian subjects.


The changing pattern of surgical pathology of the thyroid gland in Zambia. Review of reports of thyroid tissue sent for histopathology to the Department of Pathology at the University Teaching Hospital, Lusaka (UTH) by one of the five general surgical units at the institution during the period January 1981-December 1990 shows a 20pc decrease in the incidence of colloid goitre and doubling of the incidence of the adenoma and carcinoma when compared to the study done at the Central Hospital, Kitwe in the late sixties. In our study for the general pathology of the thyroid gland female to male ratio is 7.4:1; 1.25:1 when only thyroid cancers are considered. The incidence of papillary carcinoma is substantially lower than in the west. Recently, there has been an increased incidence of thyroid abscesses associated with HIV infection. Knowledge of the local pattern of surgical pathology of an organ is important for planning the operative management more effectively but in many developing countries, such as ours, this information is not readily available. Goitre is common in Zambia and to our knowledge to date there is only one comprehensive report done during the period January 1966, to March 1971. This deals with the Northern and Western regions of the country. This study was undertaken to look into the surgical pathology of the thyroid gland seen at the University Teaching Hospital, Lusaka, which is in the central part of the country.


Lassa fever: review of virology, immunopathogenesis, and algorithms for control and therapy. Lassa fever is an acute viral illness which causes consideration morbidity and mortality in the West African subregion. Recent studies have revealed that platelet and endothelial dysfunction might play a central role in the pathophysiology of this disease. Guidelines for the management of cases of the disease have recently been revised by the Centres for Disease Control, recommending care in local hospitals with use of meticulous barrier nursing techniques. This article reviews the epidemiology, immunology, pathogenesis and pathology, and current algorithms for prevention and therapy.


Congenital absence of the internal carotid artery. A case of a 27 year old male who was found to have the unusual congenital absence of one internal carotid artery is presented. A second case with similar but slightly different X-ray findings due to occlusion of the internal carotid is presented for comparison. Only forty cases of agenesis of the internal carotid artery have been found by us in the literature and this appears to be the first from Africa.


Repeat balloon aortic valvuloplasty.

Repeat balloon aortic valvuloplasty. This paper attempts to determine limitations and indications of performing a second balloon aortic valvuloplasty procedure (BAV2) because of restenosis, which is the major limitation of this technique. From September 1985 to December 1989, 357 patients underwent a primary BAV (BAV1) and 67 patients had a BAV2. Forty-two patients (group A) had repeat catheterization because they were markedly symptomatic 11 +/- 7 months after BAV1. Twenty-five patients (group B) came from a group of 73 patients who had been systematically scheduled for repeat catheterization in order to evaluate the hemodynamic restenosis rate 8 +/- 3 months after BAV. At time of BAV2 most of the patients of group A were severely disabled. Comparison of pre-BAV2 gradient and aortic valve area with pre-BAV1 measurements showed in a slightly less severe degree of aortic stenosis in group A and in group B with any difference in cardiac index and ejection fraction. Immediately following BAV2, the gradient decreased from 72 +/- 22 to 33 +/- 15 mm Hg (P less than 0.001) and aortic valve area increased from 0.56 +/- 0.18 to 0.85 +/- 0.28 cm2 (p less than 0.001) in group A. In group B, gradient decreased from 68 +/- 15 to 33 +/- 15 mm Hg (p less than 0.001) and aortic valve area increased from 0.70 +/- 0.16 to 0.90 +/- 0.25 cm2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Use of twenty-four hour infusions of intracoronary tissue plasminogen activator to increase the application of coronary angioplasty. Coronary arteries occluded by long lengths of thrombus are usually considered unattractive for angioplasty. Nine patients (8 male, mean age 50.1 years) undergoing angiography for unstable angina were found to have single vessel disease considered unsuitable for angioplasty as the vessel was occluded by a long length of thrombus. These patients were treated with 24 hr intracoronary infusions of 100 mg tPA in an attempt to make angioplasty feasible. Marked thrombolysis occurred in 7 patients who received uncomplicated infusions. One case was unsuccessful due to catheter displacement, while another had the infusion ceased due to an intracerebral bleed from a previously silent A-V malformation. This was the only major complication. Angioplasty was attempted in 6 of 7 cases where lysis had been achieved, with success in all lesions attempted. This reports shows that intracoronary tPA infused over prolonged periods produces excellent thrombolysis, making angioplasty feasible in some patients who were previously unsuitable.


Activated clotting times and activated partial thromboplastin times in patients undergoing coronary angioplasty who receive bolus doses of heparin. The accurate assessment of coagulation status is an important part of interventional procedures performed in the cardiac catheterization laboratory. While the traditional clinical means of assessing heparin anticoagulation has been with the activated partial thromboplastin time (APTT), the activated coagulation time (ACT) has come into widespread use in the catheterization laboratory as an assay of whole blood clotting time which can be performed rapidly at the bedside. The purpose of the present study was to (1) assess the anticoagulant effect of a 10,000 U bolus of heparin in PTCA patients and (2) document the relationship between ACTs and APTTs in a subset of these patients. Baseline and postheparin ACTs were measured using a HemoTec coagulation timer in 545 unselected PTCA patients. The average baseline ACT was 120 +/- 22 sec. After a 10,000 U bolus of heparin the average ACT was 249 +/- 44 sec; 58% of patients had an ACT less than 250 sec, 17% had an ACT between 250 and 275 sec, 12% had an ACT between 275 and 300 sec, and 13% had an ACT greater than 300 sec. A total of 175 paired ACT and APTT measurements were obtained in a random subset of these patients at baseline, after heparinization, and at 4-6 hr intervals after the procedure. The APTT was limited by absolute upper and lower limits of 150 and 22 sec; there were no such limits on the ACT. When limiting values were excluded, there was a strong overall correlation between ACT and APTT measurements (r = 0.92, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Transseptal catheterization update 1992. Resurgence of the transseptal procedure in the last decade has occurred coincident with the advent of therapeutic catheterizations and in particular mitral balloon vavuloplasty. As larger numbers of these procedures have been performed, experience shows that the position of intended septal puncture varies for each anticipated procedure and need not lie at the fossa ovalis, which is frequently displaced or inaccessible. Recognizing the dynamic alterations in septal and atrial anatomy that accompany the various combinations of valvular heart disease, the experienced interventionalist will use precatheterization echo and radiological techniques to enable precise and localized transseptal puncture. Using these techniques in 597 patients for valvular heart disease, we have had no deaths and a morbidity of 1.8% with the transseptal puncture.


Atrial septal puncture technique in percutaneous transvenous mitral commissurotomy: mitral valvuloplasty using the Inoue balloon catheter technique. Transseptal catheterization is a vital component of percutaneous transvenous mitral commissurotomy. Therefore, a well-executed transseptal catheterization is the key to a safe and successful percutaneous transvenous mitral commissurotomy. Two major problems inherent in atrial septal puncture for percutaneous transvenous mitral commissurotomy are cardiac perforation and puncture of an inappropriate atrial septal site. The former may lead to serious complication of cardiac tamponade and the latter to possible difficulty in maneuvering the Inoue balloon catheter across the mitral orifice. This article details atrial septal puncture technique, including landmark selection for optimal septal puncture sites, avoidance of inappropriate puncture sites, and step-by-step description of atrial septal puncture.