J Qual Clin Pract, 1994 Jun, 14(2), 111 - 4 The initial hospital management of childhood febrile convulsions: an audit; Dawson KP et al.; The records of 100 children admitted to hospital with a febrile convulsion during the years 1988-91 were studied . There were 295 investigations performed overall and all but one child had paracetamol prescribed during the hospital stay . Twenty-three per cent of the group received an antibiotic and 43% were discharged still receiving an antipyretic . Anticonvulsants were not widely used . The need for antipyretic use, the number of investigations performed and the need for children to be admitted overnight in the first instance is questioned. Am J Physiol, 1994 Jun, 266(6 Pt 1), C1754 - 63 Polyamines increase Ca2+ sensitivity in permeabilized smooth muscle of guinea pig ileum; Sward K et al.; The effects of polyamines were investigated in strips of smooth muscle from guinea pig ileum permeabilized with beta-escin (0.005%) . Spermine (1 mM) inhibited transient contractions induced in Ca(2+)-free medium by carbachol (0.1 mM) and GTP gamma S (0.1 mM) but potentiated responses to caffeine (20 mM) and D-myo-inositol 1,4,5-trisphosphate (40 microM) . At high ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid concentration (10 mM) and in the presence of A-23187 (10 microM), force at optimal and suboptimal Ca2+ concentrations was increased both by spermine and by carbachol . Spermine did not potentiate contraction in Ca(2+)-free medium or after full thiophosphorylation of the regulatory 20-kDa myosin light chains but slightly potentiated contractions produced by partial thiophosphorylation . Also, spermidine and putrescine, as well as the aminoglycoside antibiotic neomycin, increased sensitivity to Ca2+, with potency correlating with number of positive charges . After permeabilization by a high concentration (0.1%) of beta-escin, the sensitivity to Ca2+ was increased by spermine but not by GTP gamma S . In preparations permeabilized by Triton X-100, spermine slightly increased Ca2+ sensitivity but not maximal force . Tissue contents of putrescine, spermidine, and spermine in intact ileum muscle were 8, 98, and 184 nmol/g, respectively . Permeabilization by 0.005 and 0.1% beta-escin reduced spermine contents by 40 and 53%, respectively . Effects of added polyamines in permeabilized preparations may thus reflect physiological effects of endogenous polyamines modulating contraction in the intact tissue. Anesthesiology, 1994 Jun, 80(6), 1234 - 40 Is postoperative intrathecal catheter use associated with central nervous system infection? Bevacqua BK, Slucky AV, Cleary WF. BACKGROUND: Continuation of intrathecal anesthesia into the postoperative period has been limited by important safety concerns . Principal among these has been the assumption that extended intrathecal therapy leads to spinal (epidural and intrathecal) space infections . To address the role of extended intrathecal catheter therapy as a cause of infections, we cultured all intrathecal catheters used to provide postoperative analgesia . METHODS: All intrathecal catheters were inserted in the operating room using sterile technique . The catheters were used either for the duration of the patients stay in the intensive care unit or until they were no longer judged to provide a therapeutic advantage . They were removed without skin preparation . The distal 2-3 cm of the catheters was cultured using semiquantitative culture methods . Results were divided into four groups: group 1, negative culture results; group 2, ten or fewer colonies of growth; group 3, more than 10 colonies on initial plates and/or growth from broth cultures; and group 4, any bacterial growth, along with evidence of local or central nervous system infections . RESULTS: Cultures were obtained from 139 patients with a mean indwelling catheter time of 66.1 h . Group 1 (102 patients) had a mean indwelling duration of 55 h . Group 2 (26 patients) and group 3 (11 patients) had significantly longer indwelling duration (83.2 h P = .0023, 129.6 h P = < .0001, respectively) than group 1 . Cultures of cerebrospinal fluid obtained simultaneously with catheter cultures in 9 cases (5 in group 2 and 4 in group 3) showed no growth . No patient had evidence of local or central nervous system infection . Difficulty of catheter placement (number of attempts made and the number of levels explored), antibiotic administration, the composition of the postoperative infusions and the number of catheter breaks in the postoperative period were similar in each group . With the exception of two catheters in group 3, (cultured at 49 and 54 h), significant bacterial growth (more than ten colonies) was observed only after more than 96 h of indwelling duration . CONCLUSIONS: Application of semiquantitative culture methods assisted in explaining the results seen in group 2 as secondary to contamination of the catheter that occurred on removal . Higher numbers of bacteria (group 3) may define a population at increased risk for infectious complications . The results of this study do not absolutely resolve the issue of infectious risk associated with postoperative intrathecal catheter use, nor do they define a safe period beyond which the risk of continued catheter use would be unacceptable . However, it appears that limited periods of use (96 h or less) is not associated with either frequent local or spinal infections . Semiquantitative culture methods may help identify individuals (with catheter cultures yielding more than ten colonies) at increased risk for infectious complications and in need of closer observation. J Perinat Neonatal Nurs, 1994 Jun, 8(1), 59 - 73 Antifungal agents and their renal implications in the neonate; Levin RH et al.; The incidence of superficial or systemic fungal infections has been increasing in neonates . The cause of this increased susceptibility to fungal infections is due to the increased use of mechanical ventilation, indwelling catheters, broad-spectrum antibiotic therapy, parenteral nutrition, and steroid therapy . The most common organism encountered in neonatal infections is Candida species . This article will cover the etiology, signs, symptoms, diagnosis, and treatment of the usual neonatal fungal infections . Each of the antifungal agents used to treat neonates will be discussed with regard to its mechanism of action, pharmacokinetics, indications, normal and renal functional impairment dosing, and adverse effects. Zhongguo Zhong Xi Yi Jie He Za Zhi, 1994 Jun, 14(6), 349 - 51, 325 {Traditional Chinese medicine and Western medicine treatment for severe intractable head injury}; Wang XR et al.; 38 cases of severe intractable head injuries were treated by TCM-WM treatment, the survival rate was 68.4%, which was difficult or ineffective for Western medicine treatment . The author lay emphasis on taking the following measures: (1) Place nasal feeding tube in the nose as early as possible; (2) Take Zenye Tang and Shengmai Yin as chief prescription for nourishing Yin and replenishing Qi; (3) Take large dose of citicoline, Angong Niuhuang Wan and Xuefu Zhuyu Tang to promote resuscitation; (4) When pulmonary infection was serious and antibiotic ineffective, Shashen Maidong Tang and Ditan Tang etc . could be used. Neurochem Int, 1994 Jun, 24(6), 533 - 9 Is the heterologous expression of metabotropic glutamate receptors (mGluRs) an appropriate method to study the mGluR function? Experience with human embryonic kidney 293 cells transfected with mGluR1; Gabellini N et al.; The cloning of metabotropic glutamate receptors (mgluRs) has initiated a new approach to the study of their function: the introduction of mGluR cDNA into cells that do not normally express mGluRs, thus allowing the heterologous receptor expression . We have transfected human embryonic kidney (HEK) 293 cells with the full length mGluR1a cDNA and with its truncated variant which encodes the receptor termed mGluR1T (a receptor lacking the long intracellular domain and similar to the splice variant mGluR1c) . Transient transfection of HEK-293 cells with mGluR1a, but not the mGluR1T cDNA, resulted in a significant increase in inositol phosphate (IP) formation in absence of any mGluR agonists . This effect was completely dependent on the presence of extracellular calcium, and unlike the agonist-stimulated IP formation it was insensitive to pertussis toxin . The prolonged activation of IP formation might affect the cell physiology . In an attempt to obtain stably transfected cells, we transfected about 1.5 x 10(6) HEK-293 cells with the plasmid conveying the full-length mGluR1a cDNA and the neomycin-resistance gene . Only 12 clones survived the antibiotic selection, and only one of these 12 clones continued to divide . The size of mRNA from the clone was smaller than the full-length mGluR1a mRNA . The shortened mRNA, revealed in the clone, apparently encoded a functional mGluR that was sensitive to glutamate, but unlike the mGluR1a, it did not respond to 1S,3R-ACPD (1S,3R-aminocyclopentane-1,3-dicarboxylic acid) . A prudent use of the heterologous cell transfection technique is necessary in studying the function and the pharmacology of mGluRs. J Comput Aided Mol Des, 1994 Jun, 8(3), 257 - 72 Shape information from a critical point analysis of calculated electron density maps: application to DNA-drug systems; Leherte L et al.; A computational method is described for mapping the volume within the DNA double helix accessible to the groove-binding antibiotic netropsin . Topological critical point analysis is used to locate maxima in electron density maps reconstructed from crystallographically determined atomic coordinates . The peaks obtained in this way are represented as ellipsoids with axes related to local curvature of the electron density function . Combining the ellipsoids produces a single electron density function which can be probed to estimate effective volumes of the interacting species . Close complementarity between host and ligand in this example shows the method to give a good representation of the electron density function at various resolutions . At the atomic level, the ellipsoid method gives results which are in close agreement with those from the conventional spherical van der Waals approach. Hepatogastroenterology, 1994 Jun, 41(3), 290 - 3 Major hepatic resection in patients with a prosthetic heart valve receiving anticoagulation treatment; Shimada M et al.; We experienced two patients with a prosthetic heart valve, who underwent hepatic resection for hepatoma while on anticoagulation therapy . Patients with a prosthetic heart valve have the following characteristics; an increased risk of thromboembolism due to diminished anticoagulation in the perioperative period, a greater risk of endocarditis due to the artificial material in the heart, and impaired cardiopulmonary function including possible arrhythmia and heart failure . Furthermore, when such patients also have liver cirrhosis with a hepatoma, there is an increased risk of perioperative bleeding while on anticoagulation due to coagulopathy and also a risk of infection due to decreased cellular immunity . Patients with a prosthetic heart valve therefore require special care and attention whenever they have to undergo hepatic resection . With respect to anticoagulation, a minimal level is required to prevent bleeding and thromboembolism . Warfarin being administered preoperatively may be switched to heparin while closely monitoring the activated clotting time (biomaterial valve: 130-150 sec, non-biomaterial valve: 150-180 sec); the heparin should then be changed back to warfarin immediately after starting oral intake following operation . For the prevention of infection, a broad spectrum antibiotic should be used prophylactically both intra-operatively and postoperatively . The cardiopulmonary function must also be carefully monitored . For the assessment of postoperative liver function, lecithin: cholesterol acyltransferase, serum bilirubin and albumin are useful because there is no relevance of coagulation parameters such as prothrombin time under anticoagulation. Baillieres Clin Gastroenterol, 1994 Jun, 8(2), 339 - 50 Treatment of peptic ulcers from now to the millennium; Pounder RE; The present strategies for the management of peptic ulceration are well tolerated and clinically effective . Histamine H2-receptor antagonists can be used for mild to moderate disease, and proton pump inhibitors are of particular benefit for patients with severe peptic ulceration and the Zollinger-Ellison syndrome . However, none of these treatments provides protection against recurrent ulceration, except when taken as long-term continuous treatment . Long-term exposure to pharmacological agents raises problems of safety, particularly relating to a lack of intragastric acidity . In addition, the accelerated development of atrophic gastritis in patients receiving omeprazole requires investigation and assessment . It is unlikely that there will be any major development in the area of control of gastric acid secretion, except perhaps the introduction of specific immunization against gastrin . However, the clinical benefit of this strategy awaits assessment . The main area for development must be the introduction of convenient and effective regimens for the eradication of Helicobacter pylori infection . Existing regimens are either simpler and relatively ineffective, or too complicated for widespread application . Bearing in mind the long gestation period of any new drug, it seems likely that the only innovative drug that will be introduced for the management of peptic ulceration before the millennium will be ranitidine bismuth citrate, an antisecretory anti-H . pylori drug that will usually be used in combination with an antibiotic. Br J Haematol, 1994 Jun, 87(2), 308 - 16 Retroviral mediated gene transfer in chronic myelogenous leukaemia; Cornetta K et al.; Gene therapy for chronic myelogenous leukaemia (CML) may provide a therapeutic option for patients who are ineligible for bone marrow transplantation . To determine the feasibility of such an approach we evaluated the transduction efficiency of CML progenitor colonies from seven patients in chronic phase . Vector transduction was optimized using the CML-derived K562 cell line and applied to CML mononuclear cells . After vector exposure, optimal gene transfer was noted when CML mononuclear cell cultures contained stem cell factor, IL-3, GM-CSF and erythropoietin . The addition of IL-6 to this combination decreased transduction efficiency . Using these conditions, 20.4% +/- 2.4 (SE) of erythroid colonies (CFU-GEMM and BFU-E) and 20.2% +/- 4.7 of CFU-GM colonies were G418 resistant . This compares with a transduction efficiency of 5.9% +/- 1.1 and 6.4% +/- 1.5, respectively, for erythroid and CFU-GM colonies using marrow obtained from normal donors . Only a modest increase in gene transfer was noted when CML cells were stimulated with cytokines for the 24 h preceding vector exposure . Vector DNA in colonies expressing the BCR/ABL transcript was documented by performing PCR analysis on individual colonies . The relatively high gene transfer rate in CML suggests that this disease might be very suitable for gene therapy. J Reprod Med, 1994 Jun, 39(6), 485 - 8 Management of severe hemorrhagic cystitis in pregnancy . A report of two cases; Fakhoury GF et al.; Acute hemorrhagic cystitis (AHC) is gross hematuria and symptoms of cystitis . Usually a self-limiting entity, it is found mainly in children and cancer patients receiving chemotherapy or radiation . In a small number of patients, AHC can be severe and require aggressive management . We present two cases of severe acute hemorrhagic cystitis in pregnant women that led to hemorrhage, resistance to antibiotic therapy and premature labor . Continuous bladder irrigation with normal saline was attempted with success in stopping the hematuria and arresting the premature labor . Severe hemorrhagic cystitis in pregnancy may require aggressive management when associated with a significant blood loss and preterm labor. Int Orthop, 1994 Jun, 18(3), 164 - 71 Infection in massive bone allografts sterilised by radiation; Loty B et al.; Massive bone allografts sterilised by radiation have been used in our hospital since 1985 . The 164 consecutive reconstructions which we carried out before December 1990 were in equal part for tumour resections and revision arthroplasties associated with major bone defects . The allografts were used as intercalary or composite graft-prosthesis reconstructions . Fourteen (8.5%) skin sloughs or infections occurred, all but one after operations for malignant tumours . The grafts never appeared to be responsible . Infection after malignant tumour resection most commonly occurred at the knee when preoperative radiation had been used . Twenty-five reconstructions were performed in the presence of infection, which only recurred in one case . Twelve infections were treated, but 2 other patients died for other reasons within a year . One patient had to have an amputation and one had persistent infection . In the other cases, the infection healed . Only two debridements alone were successful . Removal of the graft and replacement with antibiotic-loaded cement was the most effective treatment. Aliment Pharmacol Ther, 1994 Jun, 8(3), 323 - 7 Effective treatment after failure of omeprazole plus amoxycillin to eradicate Helicobacter pylori infection in peptic ulcer disease; Labenz J et al.; METHODS: Fifty patients with relapsing or complicated Helicobacter pylori positive duodenal (n = 41) or gastric ulcer disease (n = 9) and failure of a combined treatment with omeprazole plus amoxycillin to eradicate H . pylori infection were re-treated with either oral triple therapy (bismuth subsalicylate, metronidazole, tetracycline) plus ranitidine {group I: n = 22} or high-dose omeprazole (40 mg b.d . to t.d.s.) plus amoxycillin (1 g t.d.s.) {group II: n = 28} . RESULTS: Patients of group I and II had similar demographic and clinical characteristics . The overall proportion of eradication of H . pylori infection was 81.8% in group I and 78.6% in group II (P = N.S.) as judged from negative bacterial findings by means of an urease test, specific culture and histology after modified Giemsa stain . Ulcer healing was observed in all patients after a maximum duration of 10 weeks . Ten patients on triple therapy and only one patient on omeprazole plus amoxycillin (45.5% vs . 3.6%; P < 0.001) complained of side effects without necessity of discontinuation of the study medication in either group . Twenty patients (group I: n = 10; group II: n = 10) with relapsing duodenal ulcer disease and successful cure were prospectively followed for one year without any evidence of ulcer relapse or H . pylori re-infection . CONCLUSION: Oral triple therapy plus ranitidine or high-dose omeprazole plus amoxycillin remain highly effective in eradicating H . pylori infection in patients with peptic ulcer disease and treatment failure of omeprazole/amoxycillin, but the omeprazole enhanced antibiotic monotherapy seems to be superior with regard to side effects . Thus, high-dose omeprazole/amoxycillin is recommended as the treatment of first choice in these selected patients . Triple therapy should be reserved for patients intolerant of amoxycillin. Antibiot Khimioter, 1994 Jun, 39(6), 3 - 7 {Functioning of integrative vectors, based on phage phi C 31, in the strain Streptomyces bambergiensis 712}; Soldatova LI et al.; Actinomycete integrative vectors were constructed . The vectors contain the Escherichia coli plasmid ColE1 replicon, the thiostrepton resistance gene used for selection in Streptomyces and a fragment of the phi C31 actinophage genome with integrative functions . The pS133 and PS135 vector DNAs transformed Streptomyces bambergiensis 712, a strain producing the phosphoglycolipid antibiotic moenomycin . Two types of the transformants were detected . The first type was not affected in the ability to produce moenomycin and the vector pS135 DNA was shown to integrate into the S . bambergiensis 712 genome by the site-specific pattern with the psi C31 phage DNA fragment . The second type of the transformants lost the ability to produce moenomycin . The Southern analysis and cloning of the inserted DNA indicated that in this case the vector pS135 and pS133 DNAs also integrated specifically into the genome but the integration took place not within the phage DNA fragment . Its realization was suggested to proceed via homologous recombination. Zentralbl Veterinarmed B, 1994 Jun, 41(4), 283 - 90 Effect of terdecamycin on experimentally induced Mycoplasma hyopneumoniae-infection in pigs; Ueda Y et al.; The effect of terdecamycin, a new antibiotic, was evaluated on experimentally induced Mycoplasma hyopneumoniae infection in pigs . Tylosin and josamycin were used as the positive control drugs . Five to 7-week-old pigs were inoculated intranasally with homogenate of pig lung lesions containing M . hyopneumoniae . In experiments 1 and 2, drugs were given in feed for 42 days, from 7 days before inoculation to 35 days after inoculation, and necropsy was carried out 35 days after inoculation . In experiment 3, drugs were given in feed for 10 days, from 3 days before inoculation to 7 days after inoculation and necropsy was carried out 28 days after inoculation . Drug efficacy was evaluated on the basis of clinical signs, lung lesions, (including percentage of gross lung lesion area), isolation of M . hyopneumoniae and growth performance data . The total number of days on which coughing was observed and the mean percentage of lung lesion area in pigs given feed containing terdecamycin at 50 ppm or above were lower than those in unmedicated control pigs . Average daily weight gain in terdecamycin-treated pigs was higher than that in unmedicated control pigs . Treatment with terdecamycin showed equal or better efficacy as compared with treatment with tylosin or josamycin. J Mol Recognit, 1994 Jun, 7(2), 123 - 32 (+)-CC-1065 as a probe for intrinsic and protein-induced bending of DNA; Hurley LH et al.; (+)-CC-1065 is a biologically potent DNA-reactive antitumor antibiotic produced by Streptomyces zelensis . This antibiotic covalently modifies DNA by alkylation of N-3 of adenine in the minor groove . As a structural consequence of covalent modification of DNA, the helix axis is bent into the minor groove . The drug-induced bending of DNA has similarities to intrinsic A-tract bending and the 3' adenine of A-tracts shows a unique reactivity to alkylation by (+)-CC-1065 . Upon covalent modification of A-tracts, the magnitude of bending is increased and the helix is stiffened . Using high-field NMR, hydroxyl-radical footprinting and gel electrophoresis, the molecular basis for the high reactivity of the bonding sequence 5'-AGTTA* (an asterisk indicates the covalent modification site) to (+)-CC-1065 has been shown to involve the inherent conformational flexibility of this sequence . Furthermore, these studies also demonstrate that after alkylation the drug-induced bending is focused over the TT region . By analogy with the junction bend model for A-tracts, a 'truncated junction bend model' is proposed for this structure . Last, the application (+)-CC-1065 entrapped/induced bending of DNA as a probe for the Sp1-induced bending of the 21-base-pair repeat and Mu transposase bending of the att L3 sequence is described. Chin Med Sci J, 1994 Jun, 9(2), 75 - 80 Antitumor activity of immunoconjugates composed of boanmycin and monoclonal antibody; Zhen Y et al.; Boanmycin (bleomycin A6, BM), an antitumor antibiotic, was conjugated to monoclonal antibodies including R19, H111 and CCT2 . The immunoconjugates exhibited selective cytotoxicity to related target cells including cecum cancer Hce-8693 cells, liver cancer BEL-7402 cells and leukemia CEM cells . They were highly effective against related human tumor xenografts in nude mice, and the inhibition rates by the conjugates were much higher than those by free BM . The inhibition rate by R19-BM conjugate against human cecum cancer xenografts reached 90% . BY immunoelectron microscopy, CCT2-BM conjugate showed specific binding and internalization in leukemia CEM cells . The results indicate that boanmycin-monoclonal antibody immunoconjugates are highly active both in vitro and in vivo. Chem Pharm Bull (Tokyo), 1994 Jun, 42(6), 1258 - 63 Fungal metabolites . XVII . Synthesis and NMR study of ion channel-forming peptides, trichosporin B-VIa and its derivative; Nagaoka Y et al.; A membrane-modifying peptide antibiotic, trichosporin B-VIa, having catecholamine secretion-inducing activity on bovine adrenal chromaffin cells has been synthesized . Aib14-Trichosporin B-VIa, in which Pro14 was replaced by Aib, has also been synthesized to modify the secondary structure of trichosporin B-VIa . Sequence-specific 1H-NMR assignments of both peptides in methanol were achieved by using two-dimensional NMR techniques. J Exp Med, 1994 Jun 1, 179(6), 1867 - 75 Adeno-associated virus 2-mediated high efficiency gene transfer into immature and mature subsets of hematopoietic progenitor cells in human umbilical cord blood; Zhou SZ et al.; Recombinant adeno-associated virus 2 (AAV) virions were constructed containing a gene for resistance to neomycin (neoR), under the control of either the herpesvirus thymidine kinase (TK) gene promoter (vTK-Neo), or the human parvovirus B19 p6 promoter (vB19-Neo), as well as those containing an upstream erythroid cell-specific enhancer (HS-2) from the locus control region of the human beta-globin gene cluster (vHS2-TK-Neo; vHS2-B19-Neo) . These recombinant virions were used to infect either low density or highly enriched populations of CD34+ cells isolated from human umbilical cord blood . In clonogenic assays initiated with cells infected with the different recombinant AAV-Neo virions, equivalent high frequency transduction of the neoR gene into slow-cycling multipotential, erythroid, and granulocyte/macrophage (GM) progenitor cells, including those with high proliferative potential, was obtained without prestimulation with growth factors, indicating that these immature and mature hematopoietic progenitor cells were susceptible to infection by the recombinant AAV virions . Successful transduction did not require and was not enhanced by prestimulation of these cell populations with cytokines . The functional activity of the transduced neo gene was evident by the development of resistance to the drug G418, a neomycin analogue . Individual high and low proliferative colony-forming unit (CFU)-GM, burst-forming unit-erythroid, and CFU-granulocyte erythroid macrophage megakaryocyte colonies from mock-infected, or the recombinant virus-infected cultures were subjected to polymerase chain reaction analysis using a neo-specific synthetic oligonucleotide primer pair . A 276-bp DNA fragment that hybridized with a neo-specific DNA probe on Southern blots was only detected in those colonies cloned from the recombinant virus-infected cells, indicating stable integration of the transduced neo gene . These studies suggest that parvovirus-based vectors may prove to be a useful alternative to the more commonly used retroviral vectors for high efficiency gene transfer into slow or noncycling primitive hematopoietic progenitor cells, without the need for growth factor stimulation, which could potentially lead to differentiation of these cells before transplantation. Biochemistry, 1994 May 31, 33(21), 6524 - 30 Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone . 2 . Identification of the site of alkylation by tetrahydropentalenolactone; Cane DE et al.; Incubation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with the antibiotic pentalenolactone (3) results in time-dependent, irreversible inhibition of GAPDH by modification of a single Cys residue in each subunit of the homotetrameric enzyme . Reduction of pentalenolactone with tritium gas gave {2,3,7,8-3H4}tetrahydropentalenolactone (7), which also exhibited time-dependent, irreversible inactivation of GAPDH . The site of covalent attachment of 7 was determined . Tryptic digestion of inactivated GAPDH and purification of the resultant products by reverse-phase HPLC gave a single labeled peptide . Amino acid sequence analysis of the radioactive peptide gave Ile-Val-Ser-Asn-Ala-Ser-X-Thr-Thr-Asn-(...) . This sequence is identical to the highly conserved region from Ile-143 to Asn-152 in pig muscle GAPDH, except for the active site Cys-149 to which the tetrahydropentalenolactone was covalently bound . Molecular modeling was used to compare both pentalenolactone (3) and heptelidic acid (4), a mechanistically related inactivator of GAPDH, with the normal substrate, glyceraldehyde 3-phosphate (1) . Finally, pentalenolactone was shown by reaction with model thiols to undergo epoxide ring opening exclusively by nucleophilic attack at the primary carbon, C-10. J Med Chem, 1994 May 27, 37(11), 1602 - 9 DNA sequence-specific reading by echinomycin: role of hydrogen bonding and stacking interactions; Gallego J et al.; The binding of echinomycin to DNA hexamers of the form GpApXpZpTpC, where the central XpZ step can be CpG, TpA, GpC, or ApT, has been studied by molecular modeling and molecular mechanics techniques . Interaction energies have also been calculated for the complexation of echinomycin with sequences containing the preferred central CpG step and different flanking base pairs . Besides, two more sets of sequences incorporating either 2,6-diaminopurine (DAP) or hypoxanthine in place of adenine or guanine, respectively, have been examined . The aim of this work was to evaluate the relative importance of hydrogen-bonding and stacking interactions in the association of echinomycin with DNA and further rationalize the experimental evidence . The results of these calculations are in consonance with available data from footprinting experiments and appear to support our previous hypothesis that, in addition to the crucial intermolecular hydrogen bonds in the central region, the stacking interactions involving the quinoxaline-2-carboxamide chromophores of the drug and the DNA base pairs play an important role in modulating the binding specificity of this bisintercalating antitumor antibiotic . This is most clearly seen when sequences with similar minor-groove environments are compared (e.g . CpI vs TpA or CpG vs TpDAP) . The dipole moment of N-methylquinoxaline-2-carboxamide has been measured (mu = 4.15 +/- 0.03 D) and compares very well with the calculated value (mu = 4.14 D) . The fact that G:C, I:C, A:T, and DAP:T base pairs are shown to be endowed with distinct van der Waals and electrostatic stacking properties with respect to this heteroaromatic ring system could have important implications for the design of novel DNA mono- and bis-intercalating agents. Eur J Obstet Gynecol Reprod Biol, 1994 May 18, 54(3), 177 - 80 The placental transfer of cefuroxime at parturition; Holt DE et al.; Maternal and fetal serum concentrations of cefuroxime were determined at birth in 39 women who were given a single intravenous dose of either 750 mg or 1500 mg of cefuroxime before delivery . Mean serum cefuroxime concentrations in maternal venous and umbilical venous blood were dose dependent, being significantly higher after 1500 mg of cefuroxime (55.0 mg/l, 95% CI 33.4-80.9 and 19.5 mg/l, 95% CI 9.5-26.3, respectively) than after 750 mg (14.7 mg/l, 95% CI 10.5-21.1 and 8.8 mg/l 95% CI 5.8-9.4, respectively) . Antibiotic concentration in maternal blood correlated with sampling time but a similar relationship was not found in cord blood . Fetal concentrations did not correlate with mode of delivery or initial maternal blood pressure . No relationship could be demonstrated between cefuroxime concentration in maternal or cord blood and maternal weight, maternal weight gain, birthweight of baby or volume of fluid infused prior to epidural anaesthesia . It is concluded that maternal and fetal concentrations likely to be effective for prophylaxis before delivery require a maternal dose of 1500 mg of cefuroxime and are independent of these physiological variables. Biochim Biophys Acta, 1994 May 17, 1218(1), 27 - 34 Antisuppression by a mutation in rpsM(S13) giving a shortened ribosomal protein S13; Faxen M et al.; The phenotype associated with an rpsM(S13) mutation, originally isolated in Escherichia coli in a selection for pseudoreversion of streptomycin dependence, was studied in strains lacking the original mutations for antibiotic dependence . The rpsM mutation gives a decreased translational step time and a reduced growth rate . It functions as a strong antisuppressor to both the serU(Su1) amber suppressor and the trpT(Su9) opal suppressor, whereas the tyrT(Su3) amber suppressor is much less affected . The small ribosomal subunit from the rpsM mutant shows a reduced sedimentation coefficient but is able to form apparently normal 70S ribosomes as judged by ultracentrifugational analysis . Cloning and sequencing show that the rpsM mutation is a CAG to TAG alteration at codon position 100, giving an S13 protein which is shortened by 19 amino acids at its C-terminal end . This implies that the C-terminal domain of the protein that is involved in binding to 16S ribosomal RNA should be affected. Biochem J, 1994 May 15, 300 ( Pt 1), 165 - 73 Localized chemical reactivity in DNA associated with the sequence-specific bisintercalation of echinomycin; Bailly C et al.; Four complementary footprinting and probing techniques utilizing DNAse I, methidiumpropyl EDTA (MPE).FeII, diethyl pyrocarbonate (DEPC) and KMnO4 as DNA-cleaving or DNA-modifying agents have been applied to investigate the sequence-specific binding to DNA of the antitumour antibiotic echinomycin . A 265 bp EcoRI-PvuII DNA restriction fragment excised from plasmid pBS was used as a substrate . Six regions of protection against DNAase I cleavage were located on the 265-mer: three sites encompass the sequences 5'-TCGA or 5'-GCGT and the three others contain 5'-GpG (CpC) dinucleotide sequences where the inhibition of DNAase I cutting by echinomycin is less pronounced . In contrast, MPE.FeII cleavage allows identification of only three echinomycin-binding sites on the 265-mer: two sites contain the sequence 5'-TCGA and one encompasses the sequence 5'-ACCA . Cleavage of DNA by MPE.FeII in the presence of echinomycin remains practically unaffected at the sequence 5'-GCGT, despite its identification by DNAase I as a strong site for binding the antibiotic, as well as at the two other sequences containing GpG steps . With both DNAase I and MPE.FeII, enhanced DNA cleavage is evident at AT-rich sequences in the presence of echinomycin . Enhanced reactivity towards KMnO4 and DEPC provides clear evidence for sequence-dependent conformational changes in DNA induced by the antibiotic . The experiments reveal that KMnO4 reacts most strongly with thymines located around, but not necessarily adjacent to, an echinomycin-binding site, whereas the carbethoxylation reactions caused by DEPC occur primarily at the adenine residues lying immediately 5' or 3' to the dinucleotide that denotes an echinomycin-binding site . The results reported here demonstrate that DEPC and KMnO4 serve as sensitive probes for different states of the DNA helix . It seems that the reaction with KMnO4 involves transient unstacking events, whereas the carbethoxylation reaction of DEPC requires larger-scale helix opening. J Chromatogr B Biomed Appl, 1994 May 13, 655(2), 320 - 4 Determination of fosfomycin in biological fluids by capillary electrophoresis; Leveque D et al.; A capillary electrophoresis method was developed for the determination of the antibiotic fosfomycin in serum, cerebrospinal fluid and aqueous humor . The technique uses indirect UV detection and the working buffer includes an organic cation to improve fosfomycin mobility . The electrophoretic time of migration is less than 7 min in both fluids . The limit of quantification is 2.5 and 1 microgram/ml in serum and aqueous fluids, respectively (signal-to-noise ratio = 3) . The method was validated in serum and water over the concentration range 2.5-200 micrograms/ml . The calibration graph for serum was linear with a correlation coefficient r = 0.999 . At a fosfomycin concentration of 2.5 micrograms/ml in serum, the intra- and inter-day precisions (coefficients of variation) were 5 and 5.2%, respectively . The mean recovery in serum was 94.5% (S.D . = 2.4%). Proc Natl Acad Sci U S A, 1994 May 10, 91(10), 4534 - 8 Spontaneous generation of a biradical species of neocarzinostatin chromophore: role in DNA bulge-specific cleavage; Hensens OD et al.; Detailed structure determination of the major and minor base-catalyzed degradation products of the chromophore of the enediyne anticancer antibiotic neocarzinostatin in the absence of DNA demonstrates that the enolate Michael addition reaction leading to a spirolactone cumulene intermediate is a spontaneous, stereoselective process . The implications of these findings for the mechanism of the thiol-independent, site-specific cleavage by the so-generated radical species of the drug at a DNA bulge are described. Proc Natl Acad Sci U S A, 1994 May 10, 91(10), 4519 - 23 Posttranslational modifications in microcin B17 define an additional class of DNA gyrase inhibitor; Yorgey P et al.; Drugs that inhibit the activity of DNA gyrase fall almost exclusively into two structural classes, the quinolones and the coumarins . A third class of DNA gyrase inhibitor is defined by the ribosomally synthesized peptide antibiotic microcin B17 (MccB17) . MccB17 contains 43 amino acid residues, but 14 of these are posttranslationally modified . Here we describe the characterization of the structure of these modifications . We propose that four cysteine and four serine side chains undergo condensation with the carbonyl group of the preceding residue, followed by alpha/beta dehydrogenation to yield four thiazole and four oxazole rings, respectively . The three proteins implicated in catalyzing these modifications (McbBCD) would constitute the only thiazole/oxazole biosynthetic enzymes identified . These results open up possibilities for the design of DNA gyrase inhibitors and add to the repertoire of posttranslational modifications with potential for protein engineering . Escherichia coli sbmA mutants, which lack the inner membrane protein (SbmA) involved in MccB17 uptake, were found to be resistant to bleomycin . Bleomycin is structurally unrelated to MccB17 except for the fact that it contains two thiazole rings . This suggests that thiazole rings are part of the MccB17 structure recognized by SbmA . This observation and the finding that SbmA homologs are widely conserved and can play developmental roles {Glazebrook, J., Ichige, A . & Walker, G . C . (1993) Genes Dev . 7, 1485-1497} suggest that thiazole- and oxazole-containing compounds may serve as signaling molecules for a wide variety of bacteria in diverse environments, including pathogen interactions with plant and animal hosts. Biochemistry, 1994 May 3, 33(17), 5347 - 55 Short peptide fragments derived from HMG-I/Y proteins bind specifically to the minor groove of DNA; Geierstanger BH et al.; Short peptides derived from chromosomal proteins have previously been proposed to bind specifically to the minor groove of A,T-rich DNA {for a review, see M . E . A . Churchill and A . A . Travers (1991) Trends Biochem . Sci . 16, 92-97} . Using NMR spectroscopy, we investigated the DNA binding of SPRKSPRK, which is one such A,T-specific motif . Under the conditions studied SPRKSPRK interacts only nonspecifically with d(CGCAAAAAAGGC).d(GCCTTTTTTGCG) . The peptides TPKRPRGRPKK, PRGRPKK, and PRGRP derived from the non-histone chromosomal protein HMG-I/Y, however, bind specifically to the central A,T sites of d(CGCAAATTTGCG)2 and d(CGCGAATTCGCG)2 . 2D NOE measurements show that the RGR segment of each peptide is in contact with the minor groove . The arginine side chains and the peptide backbone are buried deep in the minor groove, in a fashion generally similar to the antibiotic netropsin . Under the same conditions the peptide PKGKP does not interact with the same oligonucleotide duplexes, indicating that the arginine guanidinium groups are major determinants of the A,T specificity. Am J Otol, 1994 May, 15(3), 313 - 20 Chronic otitis media after tympanostomy tube placement caused by Mycobacterium abscessus: a new clinical entity? Franklin DJ, Starke JR, Brady MT, Brown BA, Wallace RJ Jr. Infections with nontuberculous mycobacteria (NTM) are being identified with increasing frequency, but the otologic manifestations of NTM infection are not well defined . Mycobacterium abscessus is a ubiquitous rapidly growing mycobacterium (RGM) known to cause disease by inoculation after trauma . Though reported following open heart and breast augmentation surgery, it is not recognized as a cause of sporadic post-tympanostomy tube otorrhea . This report presents detailed clinical information on six sporadic cases and partial information on 15 additional cases of ear infection caused by RGM over the past 7 years . Of these, 20 of 21 cases (95%) were attributable to M . abscessus, 14 of 21 (67%) subjects lived in a southern coastal state and 16 of 16 with available histories had previously undergone placement of tympanostomy tubes . Each isolate exhibited resistance to many antibiotics, with 50 percent exhibiting high level mutational resistance to aminoglycosides related to prior topical aminoglycoside use . Therapy was difficult, requiring debridement and prolonged antibiotic therapy . M . abscessus is a problematic infection requiring specific diagnosis and treatment and should be sought as a cause of refractory post-tympanostomy tube otorrhea. Am J Physiol, 1994 May, 266(5 Pt 1), C1440 - 52 Na-K-Cl cotransport in nystatin-treated tracheal cells: regulation by isoproterenol, apical UTP, and {Cl}i; Haas M et al.; Chloride secretion in mammalian airway epithelia is stimulated by beta-adrenergic agonists via an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent mechanism and by apical triphosphate nucleotides (ATP, UTP) via a cAMP-independent mechanism . Both types of secretagogues are known to stimulate apical Cl channels in airway cells; however, to maintain a stimulated rate of secretion, basolateral Cl influx via Na-K-Cl cotransport must be upregulated in parallel with apical Cl efflux . To examine the regulation of basolateral cotransport activity and its relationship to apical Cl efflux, we examined Cl transport in confluent primary cultures of dog tracheal epithelial cells treated with nystatin, an antibiotic that increases the permeability of plasma membranes to small monovalent ions, including Cl . By applying nystatin to the apical membrane of these cultures, apical Cl permeability could be increased to the point where transepithelial Cl transport is limited by transport across the basolateral membrane, which reflects primarily the activity of the cotransporter . In cultures of tracheal cells not treated with nystatin, transepithelial (basolateral-to-apical) 36Cl flux was increased two- to threefold by exposure to isoproterenol (5 microM, basolateral) or apical UTP (10 microM) . Apical application of nystatin (400 units/ml) increased the basal level of transepithelial 36Cl flux approximately 1.5-fold and eliminated UTP stimulation of this flux, although an approximately twofold stimulation by isoproterenol persisted . Nystatin treatment also abolished UTP stimulation of saturable, basolateral {3H}bumetanide binding, a measure of functioning Na-K-Cl cotransporters in these cells; isoproterenol stimulation of binding was only mildly inhibited by nystatin treatment . Lowering intracellular Cl concentration ({Cl}i) by incubating cultures with apical media containing nystatin and reduced {Cl} (NO3 replacement) increased both basolateral-to-apical 36Cl flux and {3H}bumetanide binding in the absence of secretagogues or cell shrinkage . The results support our previous suggestion, based entirely on {3H}bumetanide binding {M . Haas, D . G . McBrayer, and J . R . Yankaskas . Am . J . Physiol . 264 (Cell . Physiol . 32): C189-C200, 1993}, that UTP stimulation of basolateral Na-K-Cl cotransport in airway epithelial cells is entirely secondary to, and requires, an increase in apical Cl efflux, and further suggest that a decrease in {Cl}i may be a signal for cotransport activation in response to UTP . In addition, a cAMP-dependent cascade initiated by isoproterenol appears to directly stimulate the cotransporter. Ophthalmology, 1994 May, 101(5), 950 - 4 Orbital polymyositis and giant cell myocarditis; Leib ML et al.; BACKGROUND: Orbital polymyositis associated with giant cell myocarditis rarely has been reported in the literature . The authors report the clinical, neuroradiographic, and histopathologic features of the only patient to survive this usually fatal syndrome after cardiac transplantation . FINDINGS: This 22-year-old white woman presented in 1991 with periorbital redness, swelling, and pain in both eyes that was unresponsive to antibiotic therapy . Results of her examination were significant for limited extraocular movements, ptosis, erythema, edema, chemosis, and exophthalmos . Electrocardiogram and chest x-ray were normal . Orbital computed tomographic scan showed swelling of the extraocular muscles up to and including their insertions . The patient was given the diagnosis of orbital polymyositis and her condition improved clinically and radiographically while taking parenteral steroids . One month after discharge, the patient was in cardiogenic shock . Endomyocardial biopsy showed giant cell myocarditis, and the patient underwent emergent cardiac transplantation . Despite a complicated postoperative course, the patient has done remarkably well . CONCLUSION: Although this disorder is rare, this case suggests the need for a high index of suspicion for giant cell myocarditis in patients with inflammatory orbital polymyositis . In non-Graves orbital polymyositis the patient should be questioned and instructed concerning the signs and symptoms of congestive heart failure . Chest x-ray, Holter monitoring, and electrocardiogram also should be performed and be repeated with an echocardiogram if there are any cardiac symptoms . In addition, early endomyocardial biopsy should be considered in the proper clinical setting, allowing timely diagnosis and expeditious cardiac transplantation. J Comput Assist Tomogr, 1994 May-Jun, 18(3), 492 - 4 Invasive pulmonary aspergillosis occluding the descending aorta and left pulmonary artery: CT features; Hayashi H et al.; Invasive pulmonary aspergillosis (IPA) has been recognized as an infectious complication in immunocompromised patients . We present a case of IPA, which occluded the descending aorta and left pulmonary artery and led to death after antileukemic chemotherapy . Contrast-enhanced CT demonstrated thrombi in the great vessels as low attenuation areas . These thrombi became extensive despite intensive antibiotic and antifungal therapy . Microscopic examination revealed that the thrombi contained aspergillus hyphae, and occlusions of both great vessels were induced by direct extension of aspergillus . This case illustrates that IPA can be the cause of great vessel occlusion in immunocompromised patients . We describe the CT and autopsy findings of this case and emphasize the virulence of this fungus. Invest Ophthalmol Vis Sci, 1994 May, 35(6), 2809 - 14 Improved ocular penetration of gentamicin by mucoadhesive polymer polycarbophil in the pigmented rabbit; Lehr CM et al.; PURPOSE . To investigate whether polycarbophil, a mucoadhesive polymer of the poly(acrylic acid) type, would improve the ocular delivery of topically applied gentamicin . METHODS . Two gentamicin formulations of this polymer (neutralized versus non-neutralized) and an aqueous control formulation in saline were administered to the pigmented rabbit eye . Drug concentrations in plasma, as well as in cornea, bulbar conjunctiva, anterior sclera, iris-ciliary body, aqueous humor, and vitreous humor, were measured by fluorescence polarization immunoassay . RESULTS . Both polymeric formulations increased the uptake of gentamicin by the bulbar conjunctiva two times . Drug penetration into the aqueous humor was observed with only the non-neutralized polymer, probably occurring via the conjunctival-scleral pathway facilitated by intensified contact between the mucoadhesive polymer and the underlying bulbar conjunctiva . CONCLUSION . Polymers of the poly(acrylic acid) type are potentially useful for improving topical antibiotic drug delivery, particularly when irritancy potential due to low pH can be overcome. Mol Carcinog, 1994 May, 10(1), 23 - 9 Mutations in a shuttle vector exposed to activated mitomycin C; Srikanth NS et al.; The cytotoxicity of the potent antibiotic and antitumor agent mitomycin C (MMC) is due to its irreversible binding to DNA . Alkylating species generated by bioreductive activation of MMC are known to cause monoadducts and cross-links in DNA by specifically binding to guanine residues . To gain insight into how these lesions lead to base- and sequence-specific mutations, shuttle vector pSP189 was treated with MMC chemically reduced by treatment with sodium borohydride, replicated in human Ad293 cells, rescued in bacteria, and analyzed for mutations in the supF tRNA gene sequence . The MMC-induced mutations were predominantly base substitutions . Eighty-four percent of the base substitutions were transversions, with G:C-->T:A the major transversion . Single base deletions were the other major mutational event, and 77% of these were G:C deletions . Base positions 115, 123, and 163 were mutational hot spots based on the frequency of independent mutations . Identification of a single MMC adduct (presumed to be a modified G on the basis of its Rf value) and clustering of MMC-induced mutations at three GC-rich areas (nt 100-123, 152-163, and 168-176) suggested that the mutational spectrum we found was due to binding of MMC to guanine on either strand of the plasmid DNA. Am J Obstet Gynecol, 1994 May, 170(5 Pt 1), 1233 - 7 Delayed delivery of multifetal pregnancies with premature rupture of membranes in the second trimester; Arias F; OBJECTIVE: Premature rupture of membranes in multifetal gestations during the second trimester has an ominous prognosis and the majority of the fetuses die after preterm delivery . STUDY DESIGN: We used cervical cerclage, tocolysis, and antibiotic therapy after vaginal delivery of the fetus with ruptured membranes in eight patients with multifetal pregnancies to extend the intrauterine life and improve the outcome of the remaining fetuses . RESULTS: Survival of six fetuses was achieved in five of the eight pregnancies (four originally twins and one originally triplets) . The mean +/- SD gestational age of the fetuses first delivered was 19.6 +/- 2.6 weeks, and it was 26.7 +/- 6.8 weeks in the fetuses with delayed delivery (exact two-tailed p = 0.01) . The mean +/- SD birth weight of the fetuses delivered first was 306 +/- 149 gm and it was 1029 +/- 947 gm for the fetuses who had delayed delivery (exact two-tailed p = 0.05) . The mean +/- SD prolongation of pregnancy was 48.8 +/- 42.06 days (range 8 to 114 days) . CONCLUSIONS: Intervention with tocolysis, antibiotics, and cervical cerclage after delivery of the first fetus is a reasonable option for some patients with multifetal pregnancies and premature rupture membranes in the second trimester. Clin Orthop, 1994 May, (302), 231 - 4 Hematogenous osteomyelitis with inflammatory cyst formation mimicking a soft-tissue tumor; Ueng WN et al.; Reported is a case of hematogenous osteomyelitis of the femur with inflammatory cyst formation mimicking a soft-tissue tumor . A 15-year-old boy with a three-year history of a gradually enlarging soft-tissue mass of his left thigh was found to have an aborted acute hematogenous osteomyelitis complicated by an inflammatory cyst that was probably caused by inadequate antibiotic therapy . The osteomyelitis and its inflammatory cyst were treated with excisional debridement and six weeks of antibiotic therapy . The patient remains well five years later, with no clinical or radiologic evidence of recurrence . This is a new variant of chronic osteomyelitis that has not previously been reported. Minerva Cardioangiol, 1994 May, 42(5), 233 - 7 {Primary aorto-enteric communication}; Ghilardi G et al.; BACKGROUND . Primary aortoenteric communications are a rare and severe complication of abdominal aortic aneurysms or erosions by neoplastic diseases . Early diagnosis and surgical treatment are crucial . Postoperative morbidity and mortality are high . Diagnosis if often made intraoperatively, because the typical clinical feature (digestive haemorrhage, abdominal aneurysmal mass, abdominal pain) is often incomplete and critically ill patients require quick surgical decision and do not allow the use of sophisticated diagnostic tools . MATERIAL AND METHODS . Eight cases, observed through 13 years, are presented: six males and two females . Mean age was 61 years; male to female ratio was 3:1 . In four cases (50%) a herald bleeding occurred during the days preceding hospital admission . Presenting symptoms were haematemesis (63%), melaena (87%), abdominal pain (63%); six subjects (75%) presented hemorrhagic shock . Only three patients (37%) were aware to be affected with abdominal aortic aneurysm before admission . Diagnosis was always made by clinical feature and urgent laparotomy: two preoperative duodenoscopies were not diagnostic . Aortoduodenal communication occurred in six cases: one of these was secondary to erosion of the aorta by a carcinoma of the pancreas . Aortogastric communication occurred once; the remainder case was a communication between a hypogastric artery aneurysm and the last ileal loop . RESULTS . Surgical operation was carried out in emergency in seven patients: the eight (tumour of the pancreas and aortoduodenal erosion) died before operation . Enteric defect repair, aneurysmectomy and aortic grafting was performed in six cases . In the last case (hypogastric-ileal communication) ligation of the hypogastric artery and ileal segmental resection was performed . Thirty days operative mortality was 58% . CONCLUSION . Despite early recognition and operation, primary aorto-enteric communication remains a severe life threatening disease, bringing high mortality rates . These are clearly affected by shock condition, but a correct surgical technique and prolonged postoperative antibiotic medication to avoid graft infection are mandatory to minimize mortality. Semin Surg Oncol, 1994 May-Jun, 10(3), 200 - 7 Technical considerations in the surgical treatment of colon and rectal cancer; Fengler SA et al.; Surgery is the primary mode of therapy for colorectal cancer . Advances beyond exteriorization began to appear at the end of the nineteenth century . The antibiotic era brought on more advances . Dogma abounds with respect to the technical aspects of surgery for colon and rectal cancer and few randomized, prospective trials have been done to evaluate the importance of these techniques . Firmly established are the techniques of resection of lymphatic drainage of tumors, en bloc resection of invaded structures, and obtaining at least 2 cm margins of rectal cancers . Radical lymph node dissection, luminal ligation, oophorectomy, and the "No-Touch Technique" are discussed . Despite the paucity of irrefutable scientific data to support many of the described surgical techniques, differences in outcome between surgeons suggest that technique is important . There is great need for randomized, prospective trials to evaluate the multitude of techniques described for the surgical treatment of colorectal cancer. Clin Infect Dis, 1994 May, 18(5), 683 - 93 Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients; Grayson ML et al.; In a double-blind randomized trial, imipenem/cilastatin (I/C; 500 mg every 6 hours) and ampicillin/sulbactam (A/S; 3 g every 6 hours) were compared in regard to their efficacy for initial empirical and definitive parenteral treatment of limb-threatening pedal infection in diabetic patients . The major endpoints of treatment were cure (resolution of soft-tissue infection), failure (inadequate improvement, necessitating a change in antibiotic therapy), and eradication (clearance of all pathogens from the wound and any bone cultures) . Patients in the two treatment groups were similar in regard to the severity of diabetes; presence of neuropathy and peripheral vascular disease; site and severity of infection; pathogen isolated; and frequency of osteomyelitis (associated with 68% of the 48 A/S-treated infections and 56% of the 48 I/C-treated infections) . After 5 days of empirical treatment, improvement was noted in 94% of the A/S and 98% of the I/C recipients . At the end of definitive treatment (days' duration {mean +/- SD}: 13 +/- 6.5 {A/S}, 14.8 +/- 8.6 {I/C}), outcomes were similar: cure, 81% (A/S) vs . 85% (I/C); failure, 17% (A/S) vs . 13% (I/C); and eradication, 67% (A/S) vs . 75% (I/C) . Treatment failures were associated with the presence of antibiotic-resistant pathogens and possible nosocomial acquisition of infections . The number of adverse events among patients in the two treatment groups was similar: 7 in the A/S group (4 had diarrhea and 3 had rash) and 9 in the I/C group (5 had diarrhea, 2 had severe nausea, 1 had rash, and 1 had seizure) . Efficacy of A/S and I/C is similar for initial empirical and definitive treatment of limb-threatening pedal infection in patients with diabetes. J Pharm Sci, 1994 May, 83(5), 723 - 6 Renal handling of tobramycin in the isolated perfused rat kidney; Aiba T et al.; The renal handling of tobramycin (TOB), an aminoglycoside antibiotic (AG), was studied using a single-pass isolated perfused rat kidney with moment analysis . In the bolus administration study at tracer concentration (7.4 microM), 32% of the glomerular-filtrated TOB remained in the lumen, but no TOB was found in the vein . This ratio of the luminal uptake was reduced in a dose-dependent manner . Other aminoglycosides such as gentamicin inhibited this uptake, but tetraethylammonium and glucosamine had no effect . In addition, under the alkalinuria condition, TOB uptake was decreased to 67% of the control value . This indicated that TOB has mainly been taken into the renal epithelial cells from their luminal site and that this uptake process was saturable and specific for AGs which have more than one cationic group . The present findings should be helpful in developing a method to reduce the nephrotoxicity of AGs and to identify their toxicity mechanisms. Drug Metab Dispos, 1994 May-Jun, 22(3), 447 - 50 Studies on the renal excretion mechanisms of cefadroxil; Granero L et al.; The mechanisms of renal excretion of cefadroxil were investigated in conscious rats . The drug was intravenously infused at several infusion rates (0.27, 1.08, 5.40, 12.00, and 31.35 mg/hr), and the total and renal clearances were determined after the steady-state was reached . Renal clearance accounted for approximately 91% of total clearance . Renal clearance of cefadroxil increased from 2.51 +/- 0.39 to 3.57 +/- 0.43 ml/min as the steady-state cefadroxil plasma concentration increased from 1.7 +/- 0.3 to 24.4 +/- 3.8 micrograms/ml, and this has been attributed to a saturable renal tubular reabsorption of the antibiotic . The ratio of unbound cefadroxil renal clearance to glomerular filtration rate was larger than unity, which indicates that the antibiotic also undergoes active renal tubular secretion . When cefadroxil was administered together with cephalexin, an increase in the renal clearance of cefadroxil was observed, which has been attributed to a competitive inhibition of the tubular reabsorption of cefadroxil by cephalexin . A pharmacokinetic model for the renal excretion of cefadroxil was developed, and mathematical expressions showing the relationship between renal clearance and steady-state plasma concentration were deduced. Behav Neural Biol, 1994 May, 61(3), 206 - 13 2-deoxygalactose interferes with an intermediate processing stage of memory; Crowe SF et al.; The effect of 2-deoxygalactose (2-D-gal), an inhibitor of glycoprotein synthesis, on memory formation was investigated with the day-old chick trained on a single-trial passive discrimination task . 2-D-gal (10 mumol/chick) was shown to inhibit memory formation at a time before the emergence of an antibiotic-sensitive long-term memory stage . The amnestic effect of 2-D-gal was successfully prevented by galactose, and more significantly by noradrenaline . In contrast, anisomycin-induced amnesia was resistant to challenge by either galactose or noradrenaline . The results are consistent with the view that some glycoprotein involvement in memory formation occurs prior to the formation of protein synthesis-dependent long-term memory, and this role of glycoproteins may be associated with the triggering of long-term memory formation by noradrenaline. Antimicrob Agents Chemother, 1994 May, 38(5), 1079 - 84 Effect of ketoconazole on lethal action of amphotericin B on Leishmania mexicana promastigotes; Ramos H et al.; The effect of ergosterol depletion by ketoconazole on the leishmanicidal activity of the pore-forming antibiotic amphotericin B (AmB) was investigated . Leishmania mexicana promastigotes were lysed within minutes by the addition of micromolar concentrations of AmB (0.5 microM) but became insensitive to AmB after growth in the presence of ketoconazole (0.25 microM, 90 h) . Lipid chromatographic analysis indicated that under such conditions, ketoconazole depleted the major Leishmania sterols, dehydroepisterol and ergosterol . Plasma membrane vesicles prepared from ketoconazole-treated promastigotes exhibited a much reduced enhancement of their salt permeability after the addition of AmB at concentrations as high as 5 microM . This finding clearly indicates that upon ketoconazole treatment, the capacity of pore formation by the antibiotic is substantially impaired . The reduction of desmethyl sterols by ketoconazole was accompanied by a significant increase of 14-alpha-methyl sterols, but exogenous cholesterol remained unchanged . This ability of Leishmania promastigotes to incorporate cholesterol from the external medium may explain why ketoconazole-treated cells exhibited a much decreased but significative response to AmB when they were exposed to high AmB concentrations (2.5 or 5.0 microM) . Parallel measurements by using a fluorescence energy transfer method indicated that binding of AmB to ketoconazole-treated Leishmania promastigotes and heat-transformed leishmanias was also decreased but to different extents, a finding that may be related to the differences in their sterol content . The results obtained clearly indicate that the specific interaction of AmB with desmethyl sterols, such as dehydroepisterol, ergosterol, and even exogenous cholesterol, is an absolute requirement for the lethal action exerted by this polyene antibiotic on L . mexicana promastigotes. Compendium, 1994 May, 15(5), 602, 604, 606 - 14; quiz 616 Pulsatile pressure irrigation treatment of mandibular osteomyelitis; Betts NJ et al.; The usefulness of the pulsatile pressure saline irrigation system has been demonstrated in the orthopedic, surgical, and dental literature . Its use during the treatment of mandibular osteomyelitis has not been documented . The literature concerning pressure irrigation is reviewed, and the indications and technique of pulsatile pressure saline/antibiotic irrigation for the treatment of mandibular osteomyelitis are enumerated and demonstrated with two case reports . The pulsatile pressure saline/antibiotic irrigation system may be a useful adjunct to the standard therapeutic modalities of infection management and can be used during the management of mandibular osteomyelitis. Arch Esp Urol, 1994 May, 47(4), 349 - 62 {Carcinoma of the penis . What to do with the regional lymph nodes?}; Virseda Rodriguez JA et al.; From 1982 to 1990, we diagnosed and treated 23 cases of squamous cell carcinoma of the penis . The minimum follow-up was 3 years (range 3-8 years; mean 4 years) . Special emphasis was placed on the exact staging of the tumor according to the TNM classification, above all in relation to inguinal and iliac lymph node involvement, which indicates the choice of treatment and the prognosis . At the time of diagnosis, 14 patients (60.8%) had palpable inguinal lymph nodes . This was reduced to 10 patients after a 3-6 week course of antibiotic therapy . Treatment of the primary lesion is usually by partial amputation of the penis, which enables us to determine the pathological stage and the histological grade of the tumor and, consequently, our approach to the regional lymph nodes . Regional lymphadenectomy was performed early in 11 cases and delayed in 7 cases; i.e., when pathological nodes were palpable in the groin . Four patients (36.3%) had positive nodes in the first group and 6 (85.7%) in the second group . Forty percent had bilateral lymph node involvement . Overall the surgical technique carried a morbidity rate of 38.8% for skin necrosis and 33.3% for localized infections, which delayed healing but required no plastic surgery . Inguinal lymph node involvement is a major prognostic factor: when negative, our 3-year survival rate was 87.5%, which dropped to 40% when positive, despite lymphadenectomy . Currently, in relatively young patients with high stage and grade tumor, our approach is to do early bilateral ilioinguinal lymphadenectomy . Radical dissection carries an acceptable morbidity and mortality today and can benefit patients with positive nodes that may be undetected even by the best methods for clinical staging. Pediatr Cardiol, 1994 May-Jun, 15(3), 112 - 5 Persistent truncus arteriosus operated during infancy: long-term follow-up; Slavik Z et al.; Between July 1974 and October 1988 19 consecutive infants (mean age 2.7 months, range 5 days to 11.7 months) underwent surgical correction for persistent truncus arteriosus by one surgeon (J.L.M.) . Continuity between the right ventricle and pulmonary arteries was achieved with an antibiotic-sterilized aortic homograft (diameter 13-18 mm) together with patch closure of the ventricular septal defect . There were 3 early postoperative deaths (16%): 1 patient had severe aortic regurgitation, the other 2 had preoperative cardiac arrests . Of the latter, 1 had suffered severe cerebral damage, and the other developed recurrent pulmonary hypertensive crises and low cardiac output . The 16 survivors have been followed for 3.1-17.3 years (mean 7.8 years) . Four patients required subsequent replacement of the homograft for stenosis, aortic valve replacement for regurgitation, or both (3.0, 4.0, 8.5, and 12.0 years postoperatively) . Of the 16 survivors, 15 are in NYHA class I . Of the 13 patients who have not had aortic valve surgery, 9 have no evidence of stenosis or regurgitation . In the 14 children with the original homograft the median of the residual peak gradient across the right ventricular outflow tract is 15 mmHg (range 10-40 mmHg), and no patient has severe homograft regurgitation at follow-up . Repair of persistent truncus arteriosus has been achieved with low early mortality and no late mortality, which reflects excellent long-term function of the homograft . Furthermore, if truncal valve function is good at presentation, patients are unlikely to require aortic valve surgery. Zhonghua Yi Xue Za Zhi (Taipei), 1994 May, 53(5), 311 - 4 Leukemoid reaction in a child with appendiceal abscess: a case report; Wang YJ et al.; A case of appendiceal abscess presenting leukemoid reaction is reported . A seven-month-old male infant was admitted because of fever and diarrhea . Anemic conjunctiva and mild abdominal distension were the only physical findings on arrival . Progressive leukocytosis with left shift maturation was noted during hospitalization . The maximal white blood cell count was 178,000/cumm, with a high leukocyte alkaline phosphatase score . On the fourth day of admission, a palpable right lower quadrant abdominal mass with local tenderness was found . Appendiceal abscess was diagnosed by both ultrasonography and computed tomography . The infant received triple antibiotic therapy consisting of ampicillin, gentamicin, and clindamycin for 10 days; the mass disappeared two weeks later . As appendiceal abscess is a rare occurrence in infants and its production of a leukemoid reaction is even rarer, the case described here may cause a diagnostic challenge, and deserves attention from clinicians. Orthopedics, 1994 May, 17(5), 415 - 6 Elution characteristics of gentamicin-PMMA beads after implantation in humans; Nelson CL et al.; Seventeen patients had gentamicin-PMMA beads implanted for treatment of orthopedic infections . The authors found that beads implanted in patients for 3 to 36 weeks were capable of eluting high levels of antibiotic after retrieval . Beads that were implanted in patients for less than 10 weeks eluted significantly higher antibiotic levels than beads were implanted for more than 14 weeks . This study supports the local use of these beads in the treatment of musculoskeletal infections. Orthopedics, 1994 May, 17(5), 397 - 9 Timing of wound closure in severe compound fractures; Ostermann PA et al.; In a consecutive series of 1085 open fractures treated from May 1983 to July 1992, 381 severe compound fractures in 335 patients were managed with the antibiotic bead pouch technique . There were 27 grade I (marked swelling, compartment syndrome), 115 grade II, and 239 grade III open fractures (94 type IIIA, 114 type IIIB, and 31 type IIIC) . These fractures were managed with early administration of broad spectrum antibiotics, copious wound irrigation, serial debridements, and external skeletal stabilization . Tobramycin-PMMA beads were placed in the wound, and porous plastic film (Opsite, Smith and Nephew Medical, Limited, Hall, England) covered the soft tissue defect . This dressing was changed every 48 to 72 hours until wound coverage/closure could be obtained . Infection rate, either on an acute or chronic basis, was 2.6% in grade II open fractures and 8.4% in grade III compound fractures . There was no infected wound or bone in the grade I category . Those fractures that did not develop an infection were closed at a mean time of 7.6 days; those that developed an infection were closed at a mean time of 17.9 days . The difference was statistically significant (P < 0.001) . When severe open fractures are managed with the antibiotic bead pouch technique, wound closure should be obtained within 1 week to prevent infectious complications. Am J Otolaryngol, 1994 May-Jun, 15(3), 193 - 6 The effect of water exposure after tympanostomy tube insertion; Parker GS et al.; INTRODUCTION: Unprotected water exposure as a cause of otorrhea in patients with tympanostomy tubes remains controversial . Although most otolaryngologists continue to recommend either the avoidance of swimming or the use of water precautions during swimming, evidence indicates that the infection rate may not be affected by this practice . This study prospectively evaluates the possible role of unprotected water exposure in the occurrence of post-tympanostomy-tube otorrhea . MATERIALS AND METHODS: Two hundred twelve consecutive patients undergoing tympanostomy tube placement were randomized into swimming and nonswimming groups . No special precautions (eg, ear plugs, canal occlusion, antibiotic drugs) were used in either group . This incidence of otorrhea was then compared between these groups . RESULTS: One-year follow-up was obtained in 107 patients . There was no significant difference in the incidence of otorrhea or the number of otorrhea episodes between the two groups . CONCLUSIONS: Swimming is not contraindicated in patients with tympanostomy tubes, and water precautions do not decrease the incidence of otorrhea. Thorax, 1994 May, 49(5), 509 - 10 Localised pulmonary resection for bronchiectasis in hypogammaglobulinaemic patients; Cohen AJ et al.; BACKGROUND--Bronchiectasis and pulmonary infections are common in patients with hypogammaglobulinaemia . Despite intravenous gammaglobulin treatment and appropriate antibiotics, a subgroup of patients remains with persistent localised pulmonary infection in segments where bronchiectasis had developed before appropriate treatment . As such localised pulmonary suppuration (segmental or lobar) may serve as a focus for progression of bronchiectasis, surgical resection of the involved segments may be considered . The outcome of pulmonary resection in four such patients is reported . RESULTS--Surgery was well tolerated except for one postoperative empyema . Information on follow up is available from 3.5 to 5 years . All patients experienced considerable reduction of symptoms including cough, sputum production, antibiotic use, and hospital admissions . CONCLUSIONS--Surgical resection of localised bronchiectatic segments should be considered in patients with hypogammaglobulinaemia with persistent localised suppuration and symptoms refractory to medical treatment. Jpn J Cancer Res, 1994 May, 85(5), 550 - 5 Inhibition of topoisomerase II by a novel antitumor cyclic depsipeptide, BE-22179; Yoshinari T et al.; BE-22179, a novel cyclic depsipeptide antibiotic having two 3-hydroxyquinoline moieties, inhibited the DNA-relaxing activity of L1210 topoisomerase II completely at 0.08 microM . This effect was far stronger than that of VP-16 . However, it did not show any marked effect on topoisomerase II-mediated DNA cleavage . BE-22179 was ineffective in inhibiting the DNA relaxation by topoisomerase I at concentrations up to 10 microM, but showed DNA-intercalating ability (DNA unwinding) at 30 microM . The structure of BE-22179 is quite novel for a topoisomerase II inhibitor . Echinomycin, a quinoxaline antibiotic structurally related to BE-22179, interfered with DNA relaxation by topoisomerase II, though the effect was not due to inhibition of the catalytic activity of topoisomerase II but to conformational change of DNA based on its intercalation into DNA . Therefore, the potent inhibitory activity on topoisomerase II might not be a common activity of quinoxaline antibiotics, but might rather be specific to BE-22179 . BE-22179 prevented DNA synthesis as well as RNA synthesis in L1210 cells and inhibited the growth of the cells . However, it remains unclear to what extent the topoisomerase II inhibition was responsible for the cytotoxicity of BE-22179. Trans R Soc Trop Med Hyg, 1994 May-Jun, 88(3), 334 - 9 Aminosidine and its combination with sodium stibogluconate in the treatment of diffuse cutaneous leishmaniasis caused by Leishmania aethiopica; Teklemariam S et al.; Treatment of diffuse cutaneous leishmaniasis (DCL) caused by Leishmania aethiopica remains unsatisfactory as the parasite is relatively insensitive to antimonial compounds . Reports of the clinical effectiveness of aminosidine sulphate, especially in combination with sodium stibogluconate, in visceral leishmaniasis and the finding that this antibiotic is potent against L . aethiopica in vitro, prompted us to evaluate its usefulness in DCL . Two patients with long-standing, active DCL were treated for 60 d with aminosidine sulphate, 14 mg/kg/d parenterally . The skin lesions resolved completely in both patients although they relapsed subsequently . Synergism between aminosidine and stibogluconate was demonstrated in vitro against parasites isolated from the patients . This led us to administer combined therapy, aminosidine sulphate 14 mg/kg/d and sodium stibogluconate 10 mg/kg/d, to the 2 patients in relapse and to another, third patient . Treatment was continued for 2 months beyond parasitological cure . Side effects were minimal . Following treatment, a return of specific cell-mediated immunity occurred, as expressed by a moderate infiltration of lymphocytes into the lesions and by lymphocyte proliferation in vitro in the presence of live Leishmania antigen, with synthesis of interleukin-2 and interferon gamma with one patient and interleukin 4 with the other . During follow-up periods of 2 to 21 months after treatment, no sign of relapse was seen. Minerva Chir, 1994 May, 49(5), 377 - 82 {Pilonidal cysts: the state of the art and the authors' personal experiences}; Palmieri B et al.; After a historical review of the pathogenesis and several therapies suggested for the treatment of pilonidal cysts the authors report the results of a retrospective study performed in the Department of Surgery during a period of four years, with at least 12 months follow-up . This study involved 53 patients (35 males and 15 females, 23 years average age) affected by pilonidal cyst . These patients were treated for a month with antibiotic therapy and underwent surgery by general anaesthesia . Before surgery blue methylene was injected in the cyst . Between 4 months and 2 years 5.7% of operated patients relapsed . After 10 days antibiotic therapy they underwent surgery again by local anaesthesia and then they followed an open treatment protocol including collagen and silver sulfadiazine, healing by delayed wound closure . Furthermore a depilating cream for the border of the wound was suggested to the patient . These patients healed in a period between 4 weeks and 2 months . No relapses were observed after at least 12 months . In our opinion there is the rationale to suggest an open treatment of relapsed pilonidal cyst based on the use of heterologous lyophilized collagen and silver sulfadiazine: it is well accepted by the patient and effective in relapses. Arch Pediatr, 1994 May, 1(5), 481 - 8 {Pharmacokinetics of netilmicin in the first use in newborn infants with gestational ages greater than 34 weeks}; Berard E et al.; BACKGROUND . Neonatal bacterial infections are potentially lethal . The infant must be started on an antibiotic regimen to cover the organisms most frequently implicated . Since the introduction of gentamicin therapy for neonatal infections, attention has focused on aminoglycoside pharmacokinetics in these very young patients . PATIENTS AND METHODS . The pharmacokinetics parameters of netilmicin during its first administration were analysed in 22 newborn infants with a gestational age over 34 weeks, aged 1 to 3 days, in whom a maternofetal infection was suspected . Netilmicin was given intravenously at a dose of 6 mg/kg/day in two daily injections for 35 minutes . Blood concentrations of netilmicin were measured from samples taken 5, 15, 30, 60 minutes and 2 1/2, 5 1/5 and 11 1/2 hours after injection . The patients were also given cefotaxime plus ampicillin . RESULTS . The kinetics were bicompartimental: prematurity, proven infections and other perinatal factors influenced the pharmacologic parameters and it was not possible to define a predictive formula for antibiotic administration . CONCLUSION . The blood levels of netilmicin must be monitored even in infants who were not born prematurely . Because of the large distribution volume and the long half-life, we propose a dose of 6-7.5 mg/kg given once daily. Somat Cell Mol Genet, 1994 May, 20(3), 153 - 62 Membrane-bound neomycin phosphotransferase confers drug-resistance in mammalian cells: a marker for high-efficiency targeting of genes encoding secreted and cell-surface proteins; Mohler WA et al.; An efficient method for inactivating genes is the use of silent selectable markers that are expressed only after homologous recombination into the active target gene . However, use of this approach for genes encoding secreted or membrane-anchored proteins may produce hybrid proteins comprising the N-terminal signal sequence from the target gene linked to the protein conferring drug resistance . Such chimeric enzymes will be secreted, precluding selection for drug resistance . To overcome this problem, we tested the possibility of anchoring in the membrane the cytoplasmic neomycin phosphotransferase (NPT) . We constructed a fusion gene with a transmembrane domain connecting the N-terminal signal sequence of a membrane-targeted protein and the neo gene . Expression of this gene yielded G418-resistant colonies of C2C12 cells which contained assayable NPT activity . Comparison of enzyme activity in cell extract fractions verified that the active fusion protein was insoluble, presumably through localization to a membrane compartment . Transmembrane neo cassettes should serve as integration-activated markers capable of targeting genes encoding secreted or cell surface proteins. Intensive Care Med, 1994 May, 20(5), 365 - 7 Once daily dosing of netilmicin in neonatal and pediatric intensive care; Wagner BP et al.; OBJECTIVE: To examine a once daily dosing regimen of netilmicin in critically ill neonates and children . DESIGN AND SETTING: Open, prospective study on 81 antibiotic courses in 77 critically ill neonates and children, hospitalized in a multidisciplinary pediatric/neonatal intensive care unit . For combined empiric therapy (aminoglycoside and beta-lactam), netilmicin was given intravenously over 5 min once every 24 h . The dose ranged from 3.5-6 mg/kg, mainly depending upon gestational and postnatal age . Peak levels were determined by immunoassay 30 min after the second dose and trough levels 1 h before the third and fifth dose or after adaptation of dosing . RESULTS: All peak levels (n = 28) were clearly above 12 mumol/l (mean 22, range 13-41 mumol/l) . Eighty-nine trough levels were within desired limits (< 4 mumol/l) and 11 (11%) above 4 mumol/l, mostly in conjunction with impaired renal function . CONCLUSIONS: Optimal peak and trough levels of netilmicin can be achieved by once daily dosing, adapted to gestational/postnatal age and renal function. Haematologica, 1994 May-Jun, 79(3), 225 - 32 Hematological recovery after autologous bone marrow transplantation for high-grade non Hodgkin's lymphomas: a single center experience; Miggiano MC et al.; BACKGROUND . Both rhGM-CSF and rhG-CSF can accelerate hematological recovery after high-dose therapy and autologous bone marrow transplantation in patients with high grade non Hodgkin's lymphoma and reduce transplant-related morbidity after ABMT . METHODS . The clinical course of 23 non randomized patients was analyzed and compared with a historical control group of 10 patients . Ten patients received GM-CSF at a dose of 10 micrograms/kg in a 6-h IV infusion, and 13 received G-CSF at a dose of 5 micrograms/kg subcutaneously . Control patients received no GFs . RESULTS . Mean granulocytic recovery to 0.5 x 10(9)/L was obtained 13.1 +/- 3.2 days after marrow reinfusion in the G-CSF arm vs 16 +/- 2.7 in GM-CSF pts (p = 0.03) and vs 19.6 +/- 7.6 in controls (p < 0.01); this reduction led to a statistically significant shorter duration of fever and parenteral antibiotic therapy . Platelet recovery to 20 x 10(9)/L was not significantly influenced by GFs . CONCLUSIONS . These results indicate that only G-CSF accelerates hematological recovery after high-dose chemotherapy and autologous bone marrow transplantation and induces a significant decrease in terms of infection morbidity and duration of hospital stay. J Ind Microbiol, 1994 May, 13(3), 183 - 9 Biosynthesis and phosphate control of candicidin by Streptomyces acrimycini JI2236: effect of amplification of the pabAB gene; Asturias JA et al.; Biosynthesis of candicidin by Streptomyces acrimycini JI2236 was strongly inhibited by phosphate . p-Aminobenzoic acid (PABA) synthase activity, required for the synthesis of PABA, a candicidin precursor, was reduced by 72% in cells grown in medium supplemented with 7.5 mM phosphate . Hybridization studies showed that the DNA region of S . acrimycini carrying the pabAB gene (encoding PABA synthase) is very similar to the homologous region of S . griseus 3570 . S . acrimycini was easily transformed with plasmids containing the pabAB gene of S . griseus . Four transformants were studied in detail; three of the transformants synthesized higher levels of PABA synthase and two transformants produced more candicidin than control cultures transformed with pIJ699 . The fourth transformant was unable to synthesize the antibiotic . Formation of PABA synthase and candicidin production was equally sensitive to phosphate regulation in transformants with the pabAB than in the untransformed S . acrimycini strain. Hematol Oncol, 1994 May-Jun, 12(3), 101 - 10 Non-cryopreserved, limited number (1 or 2) peripheral blood progenitor cell (PBPC) collections following GCSF administration provide adequate hematologic support for high dose chemotherapy; Bezwoda WR et al.; Sixty-two patients with a variety of malignant diseases including 44 with breast cancer, seven with sarcomas, five with germ cell tumours, four with Hodgkin's disease and two with multiple myeloma received short duration, high dose chemotherapy, with non-cryporeserved peripheral blood progenitor cell rescue as treatment for malignancy . Limited, (one or two) peripheral blood precursor cell collections were performed following either cyclophosphamide, cyclophosphamide+GCSF or GCSF priming . Total nucleated cell and CD34+ cell yields were significantly higher with either of the two GCSF priming regimens as compared to cyclophosphamide only priming . Cell viability at the time or reinfusion was also enhanced by GCSF priming . Chemotherapy regimens included either high dose cyclophosphamide, mitoxantrone and VP16 (HD-CNV); high dose melphelan plus VP16; high dose BCNU, cyclophosphamide and VP16 (BCV); or high carboplatin, cyclophosphamide and VP16 (PCV) all given over 8-12 h . Non-cryopreserved blood progenitor cells, stored at 4 degrees C, were reinfused 24 h after completion of chemotherapy . Sixty-one of 62 patients showed hematologic recovery . Median time to hematologic recovery was significantly shorter for patients receiving GCSF primed cell collections . There was also significantly less hospitalization and antibiotic usage for patients receiving GCSF primed precursor cell collections . The addition of post chemotherapy GCSF did not, however, appear to enhance the rate of hematologic recovery . This study shows that simplified schedules for high dose chemotherapy administration together with simple precursor cell collection procedures provide safe and effective methods for administering myeloablative chemotherapy treatment. Am J Physiol, 1994 May, 266(5 Pt 1), C1165 - 72 Enhancement of gustatory nerve fibers to NaCl and formation of ion channels by commercial novobiocin; Feigin AM et al.; Single fibers of the rat chorda tympani nerve were used to study the mechanism of action of the antibiotic novobiocin on salt taste transduction . In the rat, novobiocin selectively enhanced the responses of sodium-specific and amiloride-sensitive chorda tympani nerve fibers (N type) without affecting more broadly responsive cation-sensitive and amiloride-insensitive fibers (E type) . In the presence of amiloride, novobiocin was ineffective at enhancing the response of N-type fibers toward sodium chloride . Novobiocin also increased the conductance of bilayers formed from neutral lipids by forming nonrectifying ion channels with low conductance (approximately 7 pS in 110 mM NaCl), long open times (several seconds and longer), and high cation selectivity . Amiloride did not alter either the conductance or kinetics of these novobiocin channels . These observations suggest that even though novobiocin is able to form cation channels in lipid bilayers, and possibly in cell membranes as well, its action on the salt-taste response is through modulation of existing amiloride-sensitive sodium channels. J Bacteriol, 1994 May, 176(10), 2877 - 84 Role of the rfe gene in the synthesis of the O8 antigen in Escherichia coli K-12; Rick PD et al.; The Escherichia coli O8 antigen is a mannan composed of the trisaccharide repeat unit -->3)-alpha-Man-(1-->2)-alpha-Man-(1-->2)-alpha-Man-(1--> (K . Reske and K . Jann, Eur . J . Biochem . 67:53-56, 1972), and synthesis of the O8 antigen is rfe dependent (G . Schmidt, H . Mayer, and P . H . Makela, J . Bacteriol . 127:755-762, 1976) . The rfe gene has recently been identified as encoding a tunicamycin-sensitive UDP-GlcNAc:undecaprenylphosphate GlcNAc-1-phosphate transferase (U . Meier-Dieter, K . Barr, R . Starman, L . Hatch, and P . D . Rick, J . Biol . Chem . 267:746-753, 1992) . However, the role of rfe in O8 side chain synthesis is not understood . Thus, the role of the rfe gene in the synthesis of the O8 antigen was investigated in an rfbO8+ (rfb genes encoding O8 antigen) derivative of E . coli K-12 mutant possessing a defective phosphoglucose isomerase (pgi) . The in vivo synthesis of O8 side chains was inhibited by the antibiotic tunicamycin . In addition, putative lipid carrier-linked O8 side chains accumulated in vivo when lipopolysaccharide outer core synthesis was precluded by growing cells in the absence of exogenously supplied glucose . The lipid carrier-linked O8 antigen was extracted from cells and treated with mild acid in order to release free O8 side chains . The water-soluble O8 side chains were then purified by affinity chromatography using Sepharose-bound concanavalin A . Characterization of the affinity-purified O8 side chains revealed the occurrence of glucosamine in the reducing terminal position of the polysaccharide chains . The data presented suggest that GlcNAc-pyrophosphorylundecaprenol functions as the acceptor of mannose residues for the in vivo synthesis of O8 side chains in E . coli K-12. Metabolism, 1994 May, 43(5), 533 - 7 Effect of FK506 on rat Leydig cell function--in vivo and in vitro study; Tai J et al.; FK506, a macrolide antibiotic, is a potent immunosuppressant and has a biological effect similar to that of cyclosporin A (CsA) . In this study, the in vivo and in vitro effects of FK506 on rat Leydig cell function were investigated . In vivo, basal testosterone levels and secretion in response to human chorionic gonadotropin (hCG) stimulation in ACl rats treated with intramuscular (IM) injections of FK506 at a dosage of 1 or 2 mg/kg/d for 14 days were not different from those of age-matched normal controls . Testicular weights (g) from rats treated with 14 injections of 1 mg/kg/d FK506 (1.08 +/- 0.08, n = 14) were similar to weights from age-matched controls (1.04 +/- 0.08, n = 14) . Similarly, Wistar (Wi) rats treated with FK506 at a dosage of 1 mg/kg/d for 2 weeks showed basal testosterone and luteinizing hormone (LH) levels and secretion in response to hCG stimulation similar to those of normal controls . Histologically, the Leydig cells and germ cells in FK506-treated animals appeared normal . In vitro, basal testosterone production and response to hCG stimulation by both ACI and Wi rat Leydig cells exposed to overnight treatment of FK506 (10 to 1,000 ng/mL) were not significantly different from those of control Leydig cells . Furthermore, the viability of the Leydig cells cultured for 3 days in FK506 was not significantly different from that of controls, and they continued to secrete testosterone at a rate similar to that of controls.(ABSTRACT TRUNCATED AT 250 WORDS) J Am Acad Dermatol, 1994 May, 30(5 Pt 2), 834 - 6 Cutaneous malacoplakia; Sarkell B et al.; Indurated, erythematous plaques of the left arm and left flank developed in a 69-year-old white man with multiorgan failure from Escherichia coli sepsis . Cutaneous malacoplakia was diagnosed . Intravenous antibiotic therapy resulted in resolution of the malacoplakia and the E . coli sepsis. Am J Pediatr Hematol Oncol, 1994 May, 16(2), 132 - 7 A case-control retrospective study of the efficacy of granulocyte-colony-stimulating factor in children with neuroblastoma; Housholder SE et al.; PURPOSE: We conducted a retrospective case-control study to examine the effect of granulocyte-colony-stimulating factor (G-CSF) on the duration of the neutrophil nadir and other clinical parameters in children with neuroblastoma . PATIENTS AND METHODS: We retrospectively reviewed 85 courses of the same chemotherapy in 16 consecutive neuroblastoma patients . The first nine patients received no growth factor and the following seven patients received G-CSF . Data obtained included days of neutropenia, fever rate and duration, hospitalization rate and duration, antibiotic duration, and infection rate . RESULTS: Patients who received G-CSF had a significant decrease in the period of neutropenia (mean 5.4 +/- 2.6 days per course vs . 11.4 +/- 4.1 days per course in the control group; p < 0.001) . There were no statistically significant differences in episodes of fever per course, rate of hospitalization per course, duration of hospitalization, or duration of antibiotic therapy . Control patients had documented infections during 16% (nine of 56) of their chemotherapy courses, whereas the patients receiving G-CSF had infections during 7% (two of 29) of their courses, but this difference was not statistically significant (p = 0.318) . We calculated that a study of 220 courses in each group would be needed to have adequate power to confirm that this difference is statistically significant . CONCLUSIONS: The administration of G-CSF in this patient population did result in fewer days of neutropenia, a finding that has been reported previously in several adult studies . However, we conclude that the clinical benefit of more rapid hematologic recovery in children remains uncertain and deserves further investigation in a large, prospective multicenter trial. Yale J Biol Med, 1994 May-Aug, 67(3-4), 81 - 95 Gastric acid secretion: activation and inhibition; Sachs G et al.; Peripheral regulation of gastric acid secretion is initiated by the release of gastrin from the G cell . Gastrin then stimulates the cholecystokinin-B receptor on the enterochromaffin-like cell beginning a calcium signaling cascade . An exocytotic release of histamine follows with concomitant activation of a C1- current . The released histamine begins the H2-receptor mediated sequence of events in the parietal cell, which results in activation of the gastric H+/K+ - ATPase . This enzyme is the final common pathway of acid secretion . The H+/K+ - ATPase is composed of two subunits: the larger alpha-subunit couples ion transport to hydrolysis of ATP, the smaller beta-subunit is required for appropriate assembly of the holoenzyme . Both the membrane and extracytoplasmic domain contain the ion transport pathway, and therefore, this region is the target for the antisecretory drugs of the post-H2 era . The 100 kDa alpha-subunit has probably 10 membrane spanning segments with, therefore, five extracytoplasmic loops . The 35 kDA beta-subunit has a single membrane spanning segment, and most of this protein is extracytoplasmic with the six or seven N glycosylation consensus sequences occupied . Omeprazole is an acid-accumulated, acid-activated, prodrug that binds covalently to two cysteine residues at positions 813 (or 822) and 892, accessible from the acidic face of the pump . Lansoprazole binds to cys321, 813 (or 822) and 892; pantoprazole binds to cys813 and 822 . The common binding site for these drugs (cys813 or 822) is responsible for the inhibition of acid transport . Covalent inhibition of the acid pump improves control of acid secretion, but since the effective half life of the inhibition in man is about 48 hr, full inhibition of acid secretion, perhaps necessary for eradication of Helicobacter pylori in combination with a single antibiotic, will require prolongation of the effect of this class of drug. Int J Radiat Oncol Biol Phys, 1994 Apr 30, 29(1), 163 - 8 Breast cellulitis after conservative surgery and radiotherapy; Rescigno J et al.; PURPOSE: Cellulitis is a previously unreported complication of conservative surgery and radiation therapy for early stage breast cancer . Patients who presented with breast cellulitis after conservative therapy are described . METHODS AND MATERIALS: Eleven patients that developed cellulitis of the breast over a 38-month period of observation are the subject of this report . Clinical characteristics of patients with cellulitis and their treatment and outcome are reported . Potential patient and treatment-related correlates for the development of cellulitis are analyzed . RESULTS: The risk of cellulitis persists years after initial breast cancer therapy . The clinical course of our patients was variable: some patients required aggressive, long-duration antibiotic therapy, while others had rapid resolution with antibiotics . Three patients suffered from multiple episodes of cellulitis . CONCLUSION: Patients with breast cancer treated with conservative surgery and radiotherapy are at risk for breast cellulitis . Systematic characterization of cases of cellulitis may provide insight into diagnosis, prevention, and more effective therapy for this uncommon complication. Biochem Pharmacol, 1994 Apr 20, 47(8), 1449 - 52 Antagonism between tamoxifen and doxorubicin in the MCF-7 human breast tumor cell line; Woods KE et al.; Tamoxifen, an antiestrogen, and doxorubicin, an anthracycline antibiotic, are each utilized alone and in combination in the treatment of breast carcinoma . In view of conflicting reports relating to the interaction between these drugs, studies were undertaken to characterize the influence of tamoxifen on growth inhibition by doxorubicin in the MCF-7 breast tumor cell line in vitro . Studies combining 5 microM tamoxifen, a clinically relevant concentration, with various concentrations of doxorubicin, indicated that this drug combination produces antiproliferative effects that appear to be less than additive . Concentration-dependent growth inhibition was analyzed further using various concentrations of tamoxifen and doxorubicin by the combination index-isobologram method; this quantitative approach provided clear evidence of antagonism between these agents, a finding with potential relevance to the treatment of breast cancer. Gene, 1994 Apr 20, 141(2), 287 - 91 Transcriptional regulation of the human H ferritin-encoding gene (FERH) in G418-treated cells: role of the B-box-binding factor; Bevilacqua MA et al.; We have analysed the molecular basis underlying the increase in ferritin heavy-chain mRNA (FERH) levels in cells exposed to the antibiotic Geneticin (G418) . Transient transfection experiments demonstrate that this increase is paralleled by an enhanced transcription driven by the promoter (pFERH) for the human FERH gene, in which the most proximal promoter element (B-box) appears to play a key role . This region is conserved in human and rat, and binds an unknown factor . The DNA-protein complex composed of B-box-binding factor and its cis-element becomes more abundant in the G418-treated cells, as compared with the untreated ones. Presse Med, 1994 Apr 16, 23(15), 694 - 8 {Cost of intensive treatment followed by autograft of circulating stem cells . Application to multiple myeloma}; Callaert S et al.; OBJECTIVES: Legitimate efforts to reduce health care costs, especially of intensive protocols including transplantation for haematological diseases, require realistic economic evaluations . We determined the direct cost of intensive chemotherapy associated with total body irradiation and autologous blood stem cell transplantation in patients with multiple myeloma . METHODS: Ten consecutive patients (7 males, 3 females) with Stage II or II multiple myeloma, who had received no prior treatment and were under the age of 55, were included in the study . Peripheral blood stem cells were collected by successive cytaphereses after a short period of aplasia induced by a CHOP protocol . During this period, the patients were in normal hospital rooms . A VAMP protocol was then administered in three 4-day sessions . Intensive therapy was started 1 month later with CCNU, etoposide, cyclophosphamide and melphalan . Total body irradiation (12 Gy) was performed on days -3, -2, -1 . Autologous grafting was done on day 0 . The intensive therapy was followed by a period of aplasia and the patients were protected in laminar flow rooms . Regular antibiotic and haematologic protocols were applied . Growth hormone was not given . The patients were seen regularly for follow-up and interferon alpha 2b was prescribed for 5 . RESULTS: The mean cost of the two year treatment was 468,392 +/- 167,467 French francs . Personnel accounted for 36% of the total cost, marrow collection 13%, blood products 9.8%, laboratory tests 8.2% and drugs 7.2% . Little data are available in the literature of comparable cost analyses in other French hospitals or in other countries . CONCLUSION: Controlled cost/benefit studies should be conducted to enable a rigorous comparison between different therapeutic strategies. Biochem J, 1994 Apr 15, 299 ( Pt 2), 451 - 8 Sequence-specific recognition of the HIV-1 long terminal repeat by distamycin: a DNAase I footprinting study; Feriotto G et al.; Pharmacological modulation of the interaction between transcription factors and target DNA sequences of cellular and viral genes could have important effects in the experimental therapy of a large variety of human pathologies . For instance, alteration of the DNA/protein interaction might be among the molecular mechanisms of action of DNA-binding drugs, leading to an inhibition of the expression of genes involved in the control of in vitro and in vivo growth of neoplastic cells and virus DNA replication . Natural oligopeptides, such as distamycin, are powerful inhibitors of the interaction between nuclear factors and target DNA sequences and, therefore, have been proposed as compounds retaining antibiotic, antineoplastic and antiviral properties . In this study we performed DNAase I footprinting analysis using a PCR product mimicking a region of the long terminal repeat (LTR) of the human immunodeficiency type 1 (HIV-1) retrovirus . The data obtained suggest that distamycin binds to different regions of the HIV-1 LTR depending on the DNA sequence . Electrophoretic mobility shift assays using both crude nuclear extracts from the Jurkat T-lymphoid cell line and the recombinant proteins transcription factor IID and Sp1 suggest that distamycin differentially inhibits the interaction of these two proteins with their specific DNA target sequences, in good agreement with the results obtained by DNAase I footprinting analysis. Biochem Biophys Res Commun, 1994 Apr 15, 200(1), 351 - 8 Neoglycoprotein conjugated liposomes as macrophage specific drug carrier in the therapy of leishmaniasis; Kole L et al.; The potential utility of neoglycoprotein conjugated multilamellar liposomes as macrophage specific drug delivery system was studied using hamycin as the model drug and visceral leishmaniasis as the model macrophage disease . Hamycin, a polyene antibiotic, was found to have a growth inhibitory effect on cultured Leishmania donovani promastigotes at a concentration of 0.05 microgram/ml . Hamycin entrapped in neoglycoprotein conjugated liposome (neohamysome) eliminated intracellular amastigotes of L . donovani in peritoneal macrophages 10 and 1.5 times more efficiently than did the free and liposome entrapped drug (hamysome), respectively . Moreover, neohamysome possibly could completely eliminate splenic intracellular parasites in a 45 day BALB/c mouse model of visceral leishmaniasis at a dose of 1.5 mg/Kg/day given for 4 consecutive days . Hamysome at a similar dose had 80% parasite suppressive effect whereas free drug could not be administered more than the dosage of 0.5 mg/Kg/day due to mortality problem . Neohamysome and hamysome were generally less toxic than the free drug as judged by erythrocyte lysis and several clinical parameters of liver toxicity . These results suggest a possible use of neoglycoprotein conjugated liposomes in macrophage-associated diseases. CMAJ, 1994 Apr 15, 150(8), 1265 - 70 Hospital policies on life-sustaining treatments and advance directives in Canada; Rasooly I et al.; OBJECTIVE: To determine the prevalence and content of hospital policies on life-sustaining treatments (cardiopulmonary resuscitation {CPR}, mechanical ventilation, dialysis, artificial nutrition and hydration, and antibiotic therapy for life-threatening infections) and advance directives in Canada . DESIGN: Cross-sectional mailed survey . SETTING: Canada . PARTICIPANTS: Chief executive officers or their designates at public general hospitals . MAIN OUTCOME MEASURES: Information regarding the existence of policies on life-sustaining treatments or advance directives and the content of the policies . RESULTS: Questionnaires were completed for 697 (79.2%) of the 880 hospitals surveyed . Of the 697 respondents 362 (51.9%) sent 388 policies; 355 (50.9%) sent do-not-resuscitate (DNR) policies (i.e., policies that addressed CPR alone or in combination with other life-sustaining treatments) . Of the 388 policies 327 (84.3%) addressed CPR alone, 28 (7.2%) addressed CPR plus other life-sustaining treatments, 10 (2.6%) addressed advance directives, and the remaining 23 (5.9%) addressed other life-sustaining treatments . Of the 355 DNR policies 1 (0.3%) stated that routine discussion with patients is required, 315 (88.7%) restricted their scope to terminally or hopelessly ill patients, 187 (52.7%) mentioned futility, 29 (8.2%) mentioned conflict resolution, 9 (2.5%) and 13 (3.7%) required explicit communication of the decision to the competent patient or family of the incompetent patient respectively, 110 (31.0%) authorized the family of an incompetent patient to rescind the DNR order, 224 (63.1%) authorized the nursing staff to do so, and 217 (61.1%) authorized physicians to do so . CONCLUSIONS: Although about half of the public general hospitals surveyed had DNR policies few had policies regarding other life-sustaining treatments or advance directives . Existing policies could be improved if hospitals encouraged routine advance discussions, removed the restriction to terminally or hopelessly ill patients, scrutinized the use of the futility standard, stipulated procedures for conflict resolution, explicitly required communication of the decision to competent patients or substitute decision-makers of incompetent patients and scrutinized the provision allowing families and health care professionals to rescind the wishes of now incompetent patients. Acta Crystallogr C, 1994 Apr 15, 50 ( Pt 4), 563 - 5 N alpha-benzyloxycarbonyl-alpha-aminoisobutyryl-glycyl-L-isoleucyl- L-leucine methyl ester monohydrate; Crisma M et al.; (Z)-Aib-Gly-L-Ile-L-Leu-OMe.H2O, C27H42N4O7.H2O, is a protected analogue of the C-terminal sequence of the membrane-active peptaibol antibiotic trichogin A IV . The peptide backbone is folded . The urethane carbonyl O atom acts as the acceptor of two intramolecular hydrogen bonds which give rise to a beta bend and to an alpha bend . The geometry of the latter is significantly distorted from that observed in alpha helices . This structure represents the first observation of an alpha bend in a protected tetrapeptide sequence. Neurosci Lett, 1994 Apr 11, 170(2), 247 - 50 The aminoglycoside G418 suppresses muscarinic receptor-activated calcium release in stably transfected murine N1E-115 neuroblastoma cells; Coggan JS et al.; The aminoglycoside G418 inhibited the release of calcium (Ca2+) from internal stores coupled to muscarinic receptors in murine N1E-115 neuroblastoma cells carrying the aminoglycoside resistance gene neomycin phosphotransferase (NPT) . No significant effect was observed on responses coupled to histamine or bradykinin receptors . Cells were transfected using the eukaryotic expression vector pH beta APr-1-neo and selected using G418 . Two groups were differentiated either in the continued presence of G418 or in the absence of G418 . Carbachol (1 mM), histamine (200 microM) and bradykinin (100 nM) were administered to cells for thirty seconds and changes in {Ca2+}i were measured with fluorescence video microscopy of single cells loaded with the Ca2+ indicator fura-2 . The effects of G418 on carbachol evoked Ca2+ release included a 73% reduction in the number of cells responding, a two fold increase in the time to reach half-maximal response, a 35% reduction of the peak {Ca2+}i in response to agonist and an elevation of resting {Ca2+}i from 99 +/- 14 nM (mean +/- S.E.M.) to 155 +/- 27 nM . Acute application (20 min) of G418 to transfected cells differentiated without G418 also reduced the percentage of cells responding to carbachol . This effect was less pronounced in non-transfected parent cells . Thus, the mechanism might involve a metabolite of G418 produced in cells expressing NPT . These results indicate that G418 attenuates Ca2+ release coupled to muscarinic receptors. Biochemistry, 1994 Apr 5, 33(13), 4086 - 92 O2-dependent cleavage of DNA by tetrazomine; Williams RM et al.; A mechanism for the reduction of molecular oxygen that results in the O2-dependent cleavage of both single-stranded and double-stranded DNA by the antitumor antibiotic tetrazomine (1) is presented . The results are discussed in the context of a redox self-disproportionation of the oxazolidine moiety of tetrazomine . Comparisons are made to the structurally analogous natural product quinocarcin (2) in which, like tetrazomine, the oxazolidine moiety is invoked in redox chemistry, which ultimately results in the reduction of molecular oxygen to superoxide. Schweiz Med Wochenschr, 1994 Apr 2, 124(13), 545 - 9 {Drug-induced (probably allopurinol) agranulocytosis . Case report and discussion}; Schar B et al.; Agranulocytosis is a rare but sometimes extremely dangerous adverse drug reaction which can be induced by almost any drug . We report the case of a 89-year-old man with a well-documented granulocyte chart, who received allopurinol in addition to preexisting therapy with cardiovascular drugs . Three weeks later agranulocytosis was found which bone-marrow biopsy indicated was drug-induced . After cessation of all drugs, isolation and antibiotic therapy, the leukocyte count returned to normal but the patient died four weeks later from progressive renal failure . A relation between allopurinol therapy and agranulocytosis was presumed . The drugs which might have caused this adverse reaction are discussed . The incidence, signs, symptoms and treatment are summarized and proposals are made concerning the action to be taken in the event of drug-induced agranulocytosis. Genitourin Med, 1994 Apr, 70(2), 84 - 9 Ceftriaxone in the treatment of chronic donovanosis in central Australia; Merianos A et al.; OBJECTIVES--To determine the effectiveness of intramuscular (IM) ceftriaxone sodium in the treatment of chronic donovanosis, and the acceptability to patients and staff of supervised outpatient treatment in rural clinics . METHODS--We collected demographic and sexual health data from participants using a standard questionnaire, and recorded their donovanosis lesions at baseline using genital diagrams . Treatment consisted of a single daily IM injection of 1 g ceftriaxone diluted in 2 ml of 1% lignocaine . Clinic staff followed patients for between three and 12 months, enabling the detection of late recurrences . SETTING--Rural Aboriginal communities in central Australia . PARTICIPANTS--The study describes eight women and four men with chronic donovanosis in detail, and summarises the outcome in 12 additional cases . All cases presented with advanced lesions which had failed to heal on the standard oral antibiotic regimens used in the region . RESULTS--The mean duration of infection was 3.0 years (SD 1.9 years), and between four and ten courses of antibiotics had been prescribed for six of the 12 patients . Patients received between 7-26g of ceftriaxone sodium . Clinical improvement was dramatic in most lesions, and four patients healed completely without recurrence after a total 7-10g of ceftriaxone . Mild recurrences responded to further ceftriaxone or short courses of oral antibiotics . Treatment was well tolerated, and both patient and staff compliance high . CONCLUSION--Donovanosis is an important cause of chronic genital ulceration in central Australia, and is potentially an important risk factor for HIV transmission in Aboriginal communities . The pharmacokinetics and safety profile of ceftriaxone make it a useful and cost-effective agent in the ambulatory management of donovanosis, especially in remote communities . Supervised multidrug regimens of two or more long-acting agents may provide the best answer in donovanosis, administered through the existing health care infrastructure. Dtsch Tierarztl Wochenschr, 1994 Apr, 101(4), 141 - 5 {The effect of treatment with vitamin E or selenium on the course of salinomycin poisoning in swine}