Am J Kidney Dis, 1993 Feb, 21(2), 172 - 9 Comparison of imipenem pharmacokinetics in patients with acute or chronic renal failure treated with continuous hemofiltration; Mueller BA et al.; The total clearance of imipenem, a carbapenem antibiotic, is reduced from approximately 230 mL/min in patients with normal renal function to approximately 50 mL/min in patients with chronic renal failure . This decline in clearance results not only from the loss of renal clearance, but also from a reduction in the nonrenal clearance from 130 to 50 mL/min . Current dosing recommendations for the administration of imipenem to patients with acute or chronic renal failure are based on this reduced clearance rate . We investigated the pharmacokinetics of imipenem in critically ill patients with acute or chronic renal failure to determine whether published dosing guidelines were applicable to both patient populations . Imipenem pharmacokinetic parameters were determined in 10 anuric patients with renal failure managed by continuous venovenous hemofiltration (CVVH) . Seven patients had acute renal failure, while the other three had preexisting chronic renal failure . Imipenem serum concentration data were incorporated into a first-order, single-compartment pharmacokinetic model . Determinations of the area under the serum concentration-time curve were made by the trapezoidal rule . Dosing regimens were calculated from clearance data to achieve a mid-dose imipenem serum concentration of 12 mg/L . The total clearance of imipenem in patients with acute renal failure (108.3 +/- 13.8 mL/min; mean +/- SD) was significantly greater than the total clearance measured in patients with chronic renal failure (64.4 +/- 10.5 mL/min; P < 0.02) . This increased clearance resulted from a greater nonrenal clearance of the drug in patients with acute renal failure (95.0 +/- 13.8 v 51.1 +/- 10.5 mL/min; P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) J Thorac Cardiovasc Surg, 1993 Feb, 105(2), 321 - 6 In situ repair of mycotic aneurysm of the ascending aorta; Pasic M et al.; Between 1969 and 1990 six patients (aged 14 to 64 years, mean 43 years) underwent in situ reconstruction for mycotic aneurysm of the ascending aorta . The primary source of infection was endocarditis in three patients (subacute bacterial endocarditis {n = one patient}, sepsis with acute endocarditis {n = one patient}), sepsis with sternal osteomyelitis in one, sepsis with purulent pericarditis in one, and generalized febrile illness in one . In five of six patients the treatment consisted of the excision of changed tissue combined with a composite graft (n = one patient), a xenopericardial patch repair (n = one patient), a Dacron graft repair and aortic valve replacement (n = one patient), a Dacron graft repair alone (n = one patient), and a lateral suture combined with double valve replacement (n = one patient) . In one patient with perforation of the mycotic aneurysm into the pulmonary artery, the place of rupture was oversewn without excision of the aortic or pulmonary artery tissue . Two patients with local pericardial inflammation were reoperated on during the hospital stay; one of them because of recurrent mycotic aneurysm of the ascending aorta at the other location and the other because of infection of the suture line after the Dacron patch repair . Antibiotic therapy was intravenously administered for 2 to 12 weeks postoperatively and continued orally for 4 to 8 weeks . The mean observation time was 6 years (range 4 months to 16 years) . There was no late graft infection, except the chronic infection of the suture line in one patient who died suddenly 4 months after the operation . There was no early death, and there were three late deaths (chronic myocardial failure, one patient, chronic renal failure, one patient, sudden death, one patient) . We concluded that in situ reconstruction for mycotic aneurysm of the ascending aorta combined with prolonged antibiotic therapy is an appropriate procedure with satisfactory early and good long-term results. Ann Emerg Med, 1993 Feb, 22(2), 256 - 8 Lemierre syndrome: the forgotten disease; Weesner CL et al.; Lemierre syndrome is characterized by an acute oropharyngeal infection, suppurative thrombophlebitis of the internal jugular vein, anaerobic sepsis, and metastatic infections . Before the discovery of antibiotics, this disease usually was fatal . We report the case of a patient with all of these findings, indicating that Lemierre syndrome still is seen today . Prompt recognition, abscess drainage, and appropriate antibiotic coverage result in complete recovery in most patients. Am J Dis Child, 1993 Feb, 147(2), 197 - 200 Eosinophilic pustular folliculitis in infancy and childhood; Duarte AM et al.; We describe nine patients with eosinophilic pustular folliculitis occurring in infancy . All patients had recurrent crops of pruritic papules primarily affecting the scalp and brow region of the face . Biopsy specimens revealed folliculitis with a predominant eosinophilic infiltrate . Bacterial and fungal cultures of pustules were negative . Most patients had leukocytosis and eosinophilia . Clinical response to topical corticosteroid and/or systemic antibiotic therapy was noted . Eosinophilic pustular folliculitis of infancy must be considered in the differential diagnosis of pustular disorders in infancy. J Neurochem, 1993 Feb, 60(2), 745 - 51 Characterization of membrane-bound and solubilized high-affinity binding sites for 5'-N-ethylcarboxamido{3H}adenosine from bovine cerebral cortex; Lorenzen A et al.; A high-affinity binding site for 5'-N-ethylcarboxamido{3H}adenosine ({3H}NECA) from bovine cerebral cortex has been characterized in its membrane-bound and solubilized state after gel filtration on Sepharose CL-6B . For detection of this site in membranes, it was necessary to remove metabolites with high affinities for this site enzymatically, e.g., adenosine by addition of adenosine deaminase and inosine by addition of nucleoside phosphorylase . The pore-forming peptide antibiotic alamethicin further enhanced binding of {3H}NECA to this site in membranes . In contrast to adenosine receptors and the adenotin-like low-affinity binding protein, this novel site was extremely sensitive against treatment with the sulfhydryl alkylating agent N-ethylmaleimide . In competition experiments, this site could be differentiated from adenosine receptors by its high affinity for adenine nucleotides and its lack of affinity for adenosine receptor antagonists . Inosine and its derivative S-(4-nitrobenzyl)-6-thioinosine were relatively potent ligands with Ki values in the high nano- and low micromolar range, respectively . We conclude that the high-affinity NECA binding site described previously in bovine striatum is not exclusively located in the striatum, but can also be detected in membrane preparations and soluble extracts of bovine brain cortex. J Lab Clin Med, 1993 Feb, 121(2), 244 - 56 Characteristics of amphotericin B-induced endothelial cell injury; Cutaia M et al.; The polyene antibiotic amphotericin B has been implicated in vascular injury in human subjects and lung injury in an animal model . Our objective was to determine whether amphotericin B directly injures endothelial cells and to investigate several possible mechanisms of injury . Confluent cultures of bovine endothelial cells were incubated with different concentrations of amphotericin B for varying time periods . Injury was assessed by using a chromium 51 release assay, adherent cell counts, and morphologic changes in the endothelial cell monolayers by phase microscopy . Amphotericin B increased 51Cr release in a dose- and time-dependent fashion . Corresponding to changes in 51Cr release, amphotericin B decreased adherent cell counts and disrupted the monolayers . Incubation with vehicle alone (sodium desoxycholate, 8.2 micrograms/ml) did not alter any of these parameters . Incubation of cells with a dose of antibiotic (1 micrograms/ml), which did not produce overt cell injury, significantly increased membrane permeability to K+ ions and activated the sodium/potassium adenosine triphosphatase (Na/K ATPase) . Inhibition of the ATPase at this same antibiotic concentration (1 micrograms/ml) produced endothelial cell injury equivalent to the magnitude of injury observed with high doses of the antibiotic (10 micrograms/ml) . In the presence of 10% fetal calf serum, the injury at 24 hours was significantly attenuated . This protective effect could not be attributed to binding of the drug by albumin because varying concentrations of bovine serum albumin in minimal essential medium without other serum constitutents had no effect on the magnitude of injury . Incubation of cells with several exogenous oxygen radical scavengers (dimethylthiourea, catalase, and mannitol) or a decrease in ambient oxygen tension during antibiotic exposure did not alter the magnitude of injury . The results demonstrate that amphotericin B directly injures endothelial cells in a dose- and time-dependent manner and demonstrate the importance of the Na/K ATPase for the maintenance of normal endothelial cell function and viability in response to this form of injury. Oncogene, 1993 Feb, 8(2), 487 - 90 p53 as a growth suppressor gene in HBV-related hepatocellular carcinoma cells; Puisieux A et al.; Mutations of the p53 detected in human hepatocellular carcinomas suggest that its inactivation is a critical step in hepatocellular carcinogenesis . In order to test whether the expression of p53 is compatible with the transformed phenotype of hepatoma cells, we transfected Hep 3B cell line with p53 expression vectors . This cell line, which contains integrated hepatitis B virus sequences, is a good model to study whether the wild-type p53 can function as a tumour suppressor gene in virus-related hepatocellular carcinoma . Wild-type and mutant p53 (Ala143)-expression vectors containing a neoR gene were used . The number of antibiotic-resistant colonies was six times lower after transfection with wild-type p53 vector as compared to the mutant vector . As measured by a specific radioimmunoassay, six of eight (75%) colonies randomly selected after mutant p53 transfections expressed the transfected mutant p53 protein . In contrast, out of eight colonies from wild-type p53-transfections, none expressed detectable p53 protein . The absence of p53 protein was due to the selective deletion of transfected wild-type p53 cDNA sequences . These studies demonstrate that the growth of hepatocellular carcinoma cells is not compatible with the expression of wild-type p53 . Therefore, p53 should be considered as a tumour suppressor gene in hepatocytes. Cancer Res, 1993 Feb 1, 53(3), 490 - 4 Induction of topoisomerase I-mediated DNA cleavage by a new indolocarbazole, ED-110; Yoshinari T et al.; ED-110 is a new semisynthetic antitumor agent derived from a novel indolocarbazole antibiotic, BE-13793C, produced by an actinomycete . ED-110 induced topoisomerase I-mediated DNA cleavage in vitro as strongly as camptothecin, whereas topoisomerase II-mediated DNA cleavage was not induced by this agent . Exposure of P388 cells to ED-110 caused a typical topoisomerase toxicity, i.e.: formation of cleavable complexes; inhibition of nucleotide synthesis rather than protein synthesis; and cell cycle arrest in G2 . ED-110 inhibited the growth of P388 cells, with a 50% growth-inhibitory concentration of 44 nM . ED-110 is distinguished from camptothecin by its very different structure and its ability to intercalate into double-stranded DNA . These results suggest that ED-110 has potential as a novel antitumor agent targeting topoisomerase I. Arch Fam Med, 1993 Feb, 2(2), 189 - 92 Hepatic abscess presenting as severe fatigue and anemia; Nguyen V et al.; We describe a 54-year-old woman who had severe anemia as the initial presentation of a pyogenic hepatic abscess . She was afebrile and denied any gastrointestinal symptoms other than anorexia . We discovered her hepatic abscess when we evaluated her for an occult malignancy as the cause of her anemia . She was treated with percutaneous drainage of her abscess and parenteral antibiotic therapy . We searched MEDLINE, a computerized database, to find other patients whose hepatic abscesses presented as anemia . Although mild anemia is a common accompaniment of pyogenic hepatic abscesses, we found no reports of patients who presented with fatigue and anemia without any of the more common symptoms of hepatic abscess, such as fever, right upper quadrant pain, malaise, or nausea . We conclude that anemia without fever or abdominal symptoms is a rare presentation of pyogenic hepatic abscess. Biochem J, 1993 Feb 1, 289 ( Pt 3), 889 - 95 Inhibition of 3-hydroxy-3-methylglutaryl-CoA synthase and cholesterol biosynthesis by beta-lactone inhibitors and binding of these inhibitors to the enzyme; Greenspan MD et al.; The beta-lactones L-659,699 {(E,E)-11-{3-(hydroxymethyl)-4-oxo-2- oxetanyl}-3,5,7-trimethyl-2,4-undecadienoic acid) and its radioactive derivative 3H-L-668,411 (the 2,3-ditritiated methyl ester of L-659,699) inhibited a partially purified preparation of rat liver cytosolic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase with an IC50 of 0.1 microM . These compounds were also found to inhibit the incorporation of {14C}acetate into sterols in cultured Hep G2 cells with an IC50 of 3 microM . New kinetic evidence indicated that inhibition of the isolated enzyme was irreversible . In contrast, sterol biosynthesis in cultured Hep G2 cells was rapidly restored upon removal of the compound from the medium of inhibited cultures, suggesting reversibility of inhibition in the cells . Radioactivity was found to be associated with a single cytoplasmic protein by SDS/PAGE of the cytoplasm of Hep G2 cells after incubation of the cells with the inhibitor 3H-L-668,411 . This protein was identified as cytoplasmic HMG-CoA synthase . Binding of the radioactive compound to the enzyme was decreased with time if the radioactive inhibitor was removed from the medium . Exposure of a gel containing the radioactive enzyme-inhibitor complex to neutral hydroxylamine also resulted in a loss of radioactivity from the gel . The purified rat liver enzyme reacted with the 3H-ligand to form a stable enzyme-inhibitor complex which could be isolated by h.p.l.c . Radioactivity was also subsequently lost from this complex when it was incubated with neutral hydroxylamine . Incorporation of {14C}acetate into cholesterol in mouse liver was inhibited in a reversible manner after oral administration of the beta-lactone inhibitor . These studies, as well as the kinetic evidence presented, suggest that the beta-lactone inhibitors acylate HMG-CoA synthase in a reaction which appears to be irreversible in vitro, but is easily reversed in cultured cells and in animals. Z Gastroenterol, 1993 Feb, 31 Suppl 2, 76 - 7 {Cholestasis in imipenem/cilastatin treatment}; Schreiber C et al.; The case report on a 22-year-old female patient shows how the treatment with Imipenan/Cilastatin resulted in a severe intrahepatic cholestasis . The serum-bilirubin rapidly decreased after discontinuation of the antibiotic . The laboratory findings were no longer conspicuous four weeks after discharge from hospital. Br Dent J, 1993 Jan 23, 174(2), 59 - 64 The dental status and attitudes of patients at risk from infective endocarditis; Smith AJ et al.; Infective endocarditis represents one of the few potentially fatal infections that may be caused in the patient by a dentist . Efforts to reduce the incidence of this disease usually take the form of appropriate antibiotic cover prior to dental treatment, together with the establishment and maintenance of good oral health . This paper is a report of a survey on the dental health and awareness of 81 'at-risk' patients attending a cardiology outpatient clinic . It was found that whilst the patients were apparently well motivated and well informed, a high prevalence of periodontal disease existed in the group . It is concluded that when patients are diagnosed with a cardiac disorder which predisposes to infective endocarditis they should have a dental examination as soon as possible, preferably by a dentist experienced in the treatment of patients with special needs. Biochemistry, 1993 Jan 19, 32(2), 463 - 71 The sugars in chromomycin A3 stabilize the Mg(2+)-dimer complex; Silva DJ et al.; Chromomycin A3 (CRA3) is a glycosylated antitumor antibiotic that binds as a dimer to the minor groove of DNA, with a Mg2+ cation (or another divalent cation with a radius less than 0.85 A) forming the center of the dimer . It has been shown that the chromose sugars are necessary for DNA binding {Kaziro & Kamiyama (1967) J . Biochem . (Tokyo) 62, 424-429; Kamiyama (1968) J . Biochem . (Tokyo) 63, 566-572}, although the reason for this has not been addressed . We have investigated the role that the chromose sugars play in metal complexation in solution (methanol) by comparing the optical behavior of CRA3 and its aglycon, CRN, in the presence of various divalent metals (Mg2+, Ni2+, and Ca2+) . The results show that CRA3 forms a dimeric complex {i.e., (CRA3)2M, where M is a metal ion} in the presence of 1 mol equiv of either Ni2+ or Mg2+ but a 1:1 complex in the presence of the much larger Ca2+ . In contrast, CRN forms a 1:1 complex (CRN.M)+ with all three metals under identical conditions (1:1 mole ratio of drug to metal) . Thus, for the smaller metal ions the sugars stabilize the 2:1 CRA3-metal complex in solution . NMR data on the 2:1 CRA3-Mg2+ complex show that the trisaccharide of one CRA3 molecule lies in close proximity to the chromophore of the other CRA3 molecule . This interaction, which is also present in the Mg(2+)-CRA3-DNA complex {Gao & Patel (1989) Biochemistry 28, 751-762}, appears to be related to the stability of the dimer in solution.(ABSTRACT TRUNCATED AT 250 WORDS) Biochemistry, 1993 Jan 19, 32(2), 613 - 21 Inhibition of Rad3 DNA helicase activity by DNA adducts and abasic sites: implications for the role of a DNA helicase in damage-specific incision of DNA; Naegeli H et al.; The yeast nucleotide excision repair gene RAD3 is absolutely required for damage-specific incision of DNA . Rad3 protein is a DNA helicase, and previous studies have shown that its catalytic activity is inhibited by ultraviolet (UV) radiation damage . This inhibition is observed when base damage is confined to the DNA strand on which Rad3 protein binds and translocates, and not when damage is present exclusively on the complementary strand . In the present study, we show that Rad3 DNA helicase activity is inhibited in an identical strand-specific fashion by bulky base adducts formed by treating DNA with the antineoplastic agent cisplatin or the antibiotic compound CC-1065, which alter the secondary structure of DNA in different ways . In addition, Rad3 helicase activity is inhibited by small adducts generated by treatment of DNA with diethyl sulfate and by the presence of sites at which pyrimidines have been lost (abasic sites) . No inhibition of Rad3 helicase activity was detected when DNA was methylated at various base positions . Cisplatin-modified single-stranded DNA and poly(deoxyuridylic acid) containing abasic sites are more effective competitors for Rad3 helicase activity than their undamaged counterparts, suggesting that Rad3 protein is sequestered at such lesions, resulting in the formation of stable Rad3 protein-DNA complexes . The observations of strand-specific inhibition of Rad3 helicase activity and the formation of stable complexes with the covalently modified strand suggest a general mechanism by which the RAD3 gene product may be involved in nucleotide excision repair in yeast. Caring, 1993 Feb, 12(2), 104 - 6 Education literature for Hispanic patients; Poss RM et al.; A patient tells his home health nurse through an interpreter that he does not understand the treatment consent form . The form is printed in English . The patient understands only Spanish . A young woman learned her child's home antibiotic therapy through a demonstration given in Spanish . She now wants to review the procedure to program the pump that controls the intravenous dose . The manual is printed in English . The young mother understands only Spanish . These examples reflect the growing communication problems facing home care workers who work in Hispanic communities. Biochem Pharmacol, 1993 Jan 7, 45(1), 93 - 9 Inhibition of the Moloney murine leukemia virus cycle at a post reverse transcriptional step by the netropsin-intercalating hybrid molecule netropsin-oxazolopyridocarbazole; Subra F et al.; In a search for new antiretroviral agents acting at the nucleic acid level, two hybrid molecules composed of a bispyrrolecarboxamide chain related to netropsin, linked to the intercalating chromophore oxazolopyridocarbazole, were tested on the cycle of a defective Moloney murine leukemia virus (M.MuLV) derived from the SVX shuttle and expressing resistance to the G418 antibiotic . The drug netropsin-oxazolopyridocarbazole (Net-OPC), which displays a binding preference to duplex DNA containing A + T bases, inhibits the retroviral replicative cycle (IC50 = 4.8 microM) . In contrast, the related molecule (bis)pyrollecarboxamide-oxazolopyridocarbazole (Bpc-OPC) devoid of sequence preference as well as the elemental components of Net-OPC, namely OPC, pentyl-OPC and netropsin, displays no significant action on the viral cycle . The estimation of cytosolic viral DNA in infected cells using quantitative polymerase chain reaction suggests that Net-OPC impairs a post retrotranscriptional step of the viral cycle. Orv Hetil, 1993 Jan 3, 134(1), 25 - 7 {Bronchoalveolar lavage in the confirmation of pulmonary involvement in chronic lymphoid leukemia}; Barzo P et al.; The authors made bronchoalveolar lavage (BAL) for explaining the origin of diffuse bilateral lung--infiltration in patients with chronic lymphoid leukaemia . On the base of lavage-fluid, the lung damage may be caused by leukaemic infiltration . The lesion has not changed by antibiotic therapy, but was radiologically cured after giving corticoids . The authors have not read about approaching chronic lymphoid leukaemic pulmonary infiltration by BAL . They call attention to the etiologic clarification of lung organs' complications in haematological aspects and outstanding role of BAL as a non-invasive method. Insect Mol Biol, 1993, 2(4), 195 - 204 Baculovirus immediate early gene promoter based expression vectors for transient and stable transformation of insect cells; Vulsteke V et al.; A recombinant plasmid vector was constructed in which the bacterial LacZ gene was placed under the control of a Bombyx mori baculovirus early promoter . The vector proved to be active in transfected cultured dipteran and lepidopteran cells . Co-transfection carried out with this recombinant plasmid vector and a plasmid containing the hygromycin phosphotransferase gene followed by selection with the antibiotic hygromycin B, resulted in stable transformation of cultured Drosophila melanogaster Schneider 2 cells . Southern blot analysis of the host cell's genomic DNA in combination with chromosomal in situ hybridization demonstrated that multiple copies of both plasmids were integrated in the host cell's genome. Acta Microbiol Bulg, 1993, 29, 26 - 8 Determination of ichthiomycin concentration by biological test with Cyprinus carpio L; Gameyska Y et al.; We have found out that one-year-old carps are extremely sensitive to ichthiomycin in concentrations between 25-125 micrograms/dm3 . This fact permitted the use of biological methods for determination of ichthiomycin concentrations in cultural medium of Streptomyces levoris 1107 or crude preparations of the antibiotic. Neurol Neurochir Pol, 1993 Jan-Feb, 27(1), 79 - 84 {Diagnosis and treatment of brain abscesses in children}; Boratynski W et al.; Fourty children were treated for brain abscess in the period 1983-1988 at the Neurosurgery Department, Children's Health Centre, Warsaw . Their age was from 4 weeks to 16 years . In 38 cases the treatment was surgical, followed by antibiotic therapy, in 2 cases only antibiotics were given . In 7 cases shunts were implanted for treatment of hydrocephalus developed in infants . Two patients died during the treatment . Problems encountered in various methods of brain abscess treatment are discussed. Dimens Crit Care Nurs, 1993 Jan-Feb, 12(1), 4 - 16 Infective endocarditis: a challenging diagnosis; Snelson C et al.; The critical care nurse plays a key role in the management and care of the patient with Infective Endocarditis . The nurse's sensitive assessment of post-operative cardiac surgery patients helps to identify this complication in the early stages so that early antibiotic therapy can improve outcomes for patients with this complication . Likewise, the nurse's assessment which uncovers a history of recent dental techniques or drug abuse helps identify this complication in newly-admitted patients . By administering and evaluating the success of antibiotic therapy the nurse helps the patient combat the Infective Endocarditis. Cancer Chemother Pharmacol, 1993, 32(3), 190 - 6 Organ distribution and tumor uptake of annamycin, a new anthracycline derivative with high affinity for lipid membranes, entrapped in multilamellar vesicles; Zou Y et al.; Annamycin (Ann) is a lipophilic, non-cross resistant anthracycline antibiotic that is easily amenable to formulation in a wide variety of liposomal carriers . We studied the organ distribution and tumor uptake of Ann entrapped in multilamellar vesicles (L-Ann), free annamycin (F-Ann), and doxorubicin (DOX) in C57BL/6 mice bearing advanced subcutaneous B16 melanoma tumors . L-Ann was composed of DMPC: DMPG: Ann at a molar ratio of 7:3:0.7 . Mean particle size was 1.88 +/- 0.89 microns, and the entrapment efficiency was 93.08% +/- 2.96% . F-Ann was prepared as a suspension (particle size < or = 0.2 microns) in 10% DMSO . Drug levels were measured by fluorescence spectrometry after extraction with chloroform . The extraction ratio ranged between 60% and 90% for both drugs in most tissues . Compared with those of DOX, organ AUCs of L-Ann were threefold higher in plasma and brain, twofold higher in liver and kidney, sixfold higher in lung, ninefold higher in spleen, and tenfold higher in B16 tumors . Compared with F-Ann, organ AUCs of L-Ann were twofold higher in plasma, liver, and B16 tumors and were twofold lower in brain . Heart AUCs were similar with all three drugs . Higher tumor uptake was associated with a faster penetration and more prolonged retention of Ann in tumor tissue compared with those of DOX . The results obtained indicate significant differences in organ distribution between L-Ann and DOX as a result of the higher affinity of Ann for lipid membranes and the use of the liposomes as a delivery system . The potential clinical relevance of the increased uptake of L-Ann in B16 tumors, lung, and brain is being investigated. Acta Neurochir (Wien), 1993, 121(1-2), 15 - 9 Stereotactic aspiration of brain abscesses: is this the treatment of choice? Stapleton SR, Bell BA, Uttley D. Despite a reduction in the mortality of patients with brain abscess since the introduction of the computed tomography (CT) scanner, controversy persists as to the preferred method of treatment for this condition . Eleven patients were treated by CT guided stereotactic aspiration of pus and appropriate antibiotic therapy . A total of 14 aspirations were performed . Ten abscesses were supratentorial and one was in the posterior fossa . In 9 patients a bacterial cause was identified while in 2 a fungus was identified . A good outcome was achieved in 7 patients but 3 patients died . Another elderly patient remains disabled at home . The deaths occurred in severely systemically ill patients with poor conscious levels on admission . Only one patient has epilepsy, controlled with anticonvulsants while another has not had further seizures since abscess treatment a year ago . Stereotactic aspiration should be considered the treatment of choice in all but the most superficial and largest cerebral abscesses, although the mortality of this condition in the severely ill remains high. Instr Course Lect, 1993, 42, 405 - 13 Use of allografts following resection of tumors of the musculoskeletal system; Sim FH et al.; Allografts are an effective method of reconstructing defects following the resection of benign or malignant tumors . The surgeon must carefully plan the procedure in two stages . Stage I involves resection of the tumor with an adequate margin to prevent local recurrence, and stage II involves reconstruction of the limb with a durable and functional technique that has a low risk of morbidity . Allograft reconstructions are technically demanding . The prerequisites to a successful reconstruction include rigid internal fixation of the allograft, competent soft tissues to cover the graft, preoperative and postoperative antibiotic coverage, meticulous hemostasis and postoperative wound drainage to prevent hematoma formation, and protection of the allograft to allow union . Whenever soft-tissue coverage of the graft is in question, local rotational flaps or free microvascular transfers should be used to cover the allograft with healthy muscle . Second surgical procedures, such as revision of necrotic soft-tissue flaps, drainage of hematomas, bone grafting of nonunions, and revision of internal fixation, should be avoided by careful technique at the index operation because additional procedures place the allograft at risk for infection . Further basic science investigations and clinical studies should expand the applications of allograft reconstructions and lower the incidence of complications. Clin Exp Obstet Gynecol, 1993, 20(1), 23 - 6 Infectious morbidity in gynecologic oncologic surgery . A clinical and economic evaluation; Franchi M et al.; In the Department of Obstetrics and Gynecology, Faculty of Medicine, Varese, between March 1991 and February 1992, 70 consecutive patients undergoing elective oncologic surgery were evaluated for rationalizing the use of antibiotics in order to reduce the cost of infectious complications . We divided our patients into two groups: a high infection risk group and a low infection risk group . Our findings show that: the HIR group shows a higher antibiotic cost than LIR one; our selection criteria for HIR patients are probably correct; in the LIR group 46.6% of patients were not submitted to any antibiotic therapy. J Dermatol Surg Oncol, 1993 Jan, 19(1), 30 - 6 The running locked intradermal suture . A cosmetically elegant continuous suture for wounds under light tension; Wong NL; A new suture technique, the running locked intradermal suture, is introduced . The suture is continuous and buried, and is designed for closing simple elliptical wounds under light tension in which a good cosmetic result is desired . It is used in conjunction with a topical antibiotic and a transparent dressing . This technique reduces the dermal dead space, achieves close approximation of the epidermal wound edges, has a good cosmetic appearance soon after surgery, reduces necessary postoperative wound care, reduces the risk of wound infection in clean surgical wounds, and obviates suture removal . Three examples of its application on the face are presented . It is compared with frequently used standard wound closure methods are discussed. Cancer Chemother Pharmacol, 1993, 31(6), 485 - 8 An in vivo and in vitro trial of aclarubicin in metastatic breast cancer: a novel approach to the study of analogs; Natale RB et al.; Aclarubicin is an anthracycline antibiotic that differs from doxorubicin in its structure, mechanism of action, and preclinical toxicity profile, especially its reduced cardiotoxicity . We therefore conducted a side-by-side in vivo and in vitro trial of this agent in metastatic breast-cancer patients and their biopsied tumor specimens, respectively . Aclarubicin (100 mg/m2) was given by intravenous infusion every 3 weeks to 22 patients with objectively measurable metastatic breast cancer, 15 of whom had not previously received doxorubicin . The dose-limiting toxicity consisted primarily of leukopenia and severe nausea and vomiting . No objective response was observed in the 19 evaluable patients . After disease progression, 10 of the 15 doxorubicin-naive patients were treated with doxorubicin; 6 patients achieved a partial response, including 4 who responded to doxorubicin alone and 2 who responded to doxorubicin in combination with thiotepa and vinblastine . Tumor specimens were obtained from 14 of the 22 patients prior to the start of therapy and were tested for in vitro sensitivity to aclarubicin and doxorubicin using a soft agar colony-forming assay . Adequate colony growth occurred in 9 of 14 cultured tumor specimens . All 9 specimens, including 3 obtained from doxorubicin-naive patients, demonstrated in vitro resistance to aclarubicin . In all, 1 of 3 specimens taken from doxorubicin-naive patients demonstrated in vitro sensitivity to doxorubicin, whereas 6 tumor specimens obtained from patients who had undergone prior doxorubicin therapy demonstrated in vitro resistance . The patient whose tumor demonstrated in vitro doxorubicin sensitivity responded to a doxorubicin regimen after failing aclarubicin treatment; in vitro doxorubicin resistance correlated with clinical resistance in all cases . We conclude that aclarubicin is inactive in metastatic breast cancer at the dose and schedule used . Side-by-side in vivo and in vitro trials are feasible and could be useful in the development of investigational agents with activity greater than that of aclarubicin and, particularly, in the evaluation of analogs of clinically active drugs. Acta Paediatr, 1993 Jan, 82(1), 119 - 21 D-lactic acidosis: a treatable encephalopathy in pediatric patients; Gurevitch J et al.; A 20-month old infant, who had short bowel syndrome following extensive surgery for a mid gut volvulus, developed hyperchloremic acidosis, with a large anion gap after enteral feeding was instituted . The organic acidosis was at least partly due to an increased concentration of D-lactic acid . This patient, as did five other pediatric patients, presented with a typical encephalopathy syndrome . Early recognition of this syndrome and treatment with an intestinal antibiotic and discontinuation of enteral feeding enabled prompt correction of the hyperchloremic acidosis and a rapid clinical recovery. Arzneimittelforschung, 1993 Jan, 43(1), 60 - 70 General pharmacology of loracarbef in animals; Shetler T et al.; Loracarbef ((6R, 7S)-7-{(R)-2-amino-2-phenyl-acetamido}-3-chloro-8-oxo-1- azabicyclo {4.2.0}oct-2-ene-2-carboxylic acid, monohydrate, LY 163892, CAS 121961-22-6) is a carbacephem antibiotic targeted for use in the treatment of infectious disease . The potential pharmacological effects of this agent were examined on cardiovascular, respiratory, gastrointestinal, central nervous and autonomic nervous systems . Also examined were local anesthetic activity, effects on platelet aggregation, circulating blood glucose, primary antibody production, renal function, blood coagulation, ocular irritation, and the acute inflammatory response . Doses of 100, 1000, and 2000 mg/kg given by the oral route were selected for most in vivo studies . Concentrations up to 3 x 10(-3) mol/l were used in vitro . Loracarbef was essentially inactive in the tests of central and autonomic nervous system function, platelet aggregation, renal function, blood hemolysis, primary antibody production, blood coagulation, and ocular irritation . It had no local anesthetic activity . At high oral or intravenous doses, representing significant multiples of the therapeutic dose, loracarbef caused changes in gastrointestinal (decrease in gastric acid production and gastric fluid volume; increased biliary output), cardiovascular (increased mean pressure, cardiac output, heart rate, and femoral flow), blood glucose (increased glucose levels), and anti-inflammatory tests (suppressed acute inflammatory response) . In summary, loracarbef exhibited minimal activity in these pharmacodynamic studies . These results indicate loracarbef has a low potential to produce adverse effects at therapeutic doses. J Appl Physiol, 1993 Jan, 74(1), 423 - 7 Protective effects of anti-O polysaccharide and anti-lipid A monoclonal antibodies on pulmonary hemodynamics; Chen TY et al.; Monoclonal antibodies (MAbs) directed to endotoxin can protect in some animal models against the pathophysiological effects of endotoxin infusion . When 0.02 microgram/kg of lipopolysaccharide (LPS) derived from Escherichia coli O111:B4 was incubated in vitro for 2 h with the murine immunoglobulin G MAb, 5B10, directed against the O-polysaccharide antigenic domain of E . coli O111:B4 and then the mixture was infused into sheep, we noted significant protection . The second temperature peak was decreased (P < 0.05 vs . LPS control) . The acute pulmonary arterial pressure elevation was diminished (mean peak pulmonary arterial pressure 23.2 +/- 2.5 mmHg, P < 0.05 vs . LPS control), and the peak plasma thromboxane B2 level was reduced (mean peak thromboxane B2 level 0.50 +/- 0.15 ng/ml, P < 0.05 vs . LPS control) . In contrast, preincubation of the LPS with a human immunoglobulin M MAb, HA-1A, directed against the core glycolipid of the LPS molecule provided no protective effects in this sheep model . This finding is in agreement with recent studies reporting HA-1A may bind to antibiotic-treated bacteria but not to purified smooth LPS. Cancer Immunol Immunother, 1993, 36(3), 177 - 84 The role of monoclonal antibody A7 as a drug modifier in cancer therapy; Kitamura K et al.; An anticancer antibiotic, neocarzinostatin (NCS), was covalently conjugated to the murine monoclonal antibody A7 (mAb A7), which recognizes the glycoprotein on the cell surface of human colon cancer . The biological and pharmacological properties of the conjugate (A7-NCS) were examined and compared with those of unconjugated NCS . A7-NCS exhibited a strong binding and cytotoxicity to the cell and an antigen-specific tumor accumulation . Significant tumoricidal effects in vivo were observed in the antigen-positive tumor-bearing mice treated with A7-NCS, whereas NCS mixed with mAb A7 and NCS alone were relatively ineffective . In the antigen-negative tumor, the tumoricidal effect of A7-NCS was lower than in the antigen-positive tumor . The NCS concentration in blood and tumor were significantly elevated by conjugation to mAb A7 . The NCS localization in tumor was higher in the antigen-positive tumor than in the antigen-negative tumor . Death due to acute toxicity was observed at a dose of 20 units (U) NCS in mice treated with unconjugated NCS, whereas toxicity was seen with a much higher dose of NCS (100 U) if the drug was conjugated to the mAb . These findings show that mAb A7 confers more favorable pharmacological properties on an anticancer drug, making it potentially more useful for cancer chemotherapy. An Esp Pediatr, 1993 Jan, 38(1), 13 - 6 {Blastocystis hominis and abdominal pain in childhood}; Fleta Zaragozano J et al.; We report the clinical features observed in 10 children, ranging from 5 1/12 to 13 7/12 years of age, with intestinal infections caused by Blastocystis hominis . A parasitological study of the stools was made by using the ethyl-acetate formol concentration technique and a count of the number of B . hominis per field was performed . In 8 of the cases, no other enteropathogens (viruses, bacteria or other parasites) were found, whereas in 2 cases Giardia lamblia was also isolated . Nine out of ten of the patients presented with abdominal pain . In three of the cases it appeared as a pseudo-appendicular ailment which led to an appendectomy . Those children who were treated with metronidazole and those who were not treated with antibiotic recovered satisfactorily. Chirurg, 1993 Jan, 64(1), 58 - 62 {Fournier's gangrene}; Ecker KW et al.; Today Fournier's gangrene ranks among necrotizing fasciitis . Most of the cases reveal the origin of the disease (proctogenic, urologic, gynecologic) . Untreated, the polybacterial synergistic infection will overwhelmingly spread along anatomically defined fascias of the pelvic floor . Thus the lethality rate is high, especially in patients with risk factors i.e . diabetes, alcoholism, arterial occlusive disease, chronic consumptive disorders and obesity . Only by instant and radical surgical excision of the total gangrenous tissue the spreading of the disease and the developing of sepsis can be stopped together with calculated antibiotic therapy and intensive care . Mutilating operations (i.e . penectomy, orchiectomy) are seldom necessary; thus plastic reconstructions will show good results both in function and cosmetic . Based on the experience with 6 patients, a pathogenic concept, concerning both diagnosis and therapy, is presented: after radical emergency surgery in the first risky stage, an elective approach can safely be performed in a second stage for the repair of functional lesions. Cancer Chemother Pharmacol, 1993, 31(5), 395 - 400 Phase I clinical study of LL-D49194 alpha 1 with retrospective pharmacokinetic investigations in mice and humans . The EORTC ECTG; Cassidy J et al.; LL-D49194 alpha 1 is a new cytotoxic antibiotic selected for clinical phase I study because of its impressive pre-clinical anti-tumour activity and its low toxicity profile in experimental animals . A total of 15 patients were treated in centres in Glasgow and Amsterdam at doses ranging from 0.25 to 4 mg/m2 . One minor response was noted in a patient with colonic carcinoma . The study was suspended following the discovery of unexpected cardiotoxicity . As this toxicity was not consistent with the standard (EORTC) European Organisation for Research and Treatment of Cancer toxicology profile, we chose to investigate the pharmacokinetics of LL-D49194 alpha 1 in mice and humans in more detail to try to explain this phenomenon . A major difference in plasma protein binding was discovered between mice and patients, with a suggestion of non-linear kinetics being noted at higher doses in humans . It is likely that these differences in drug handling account for the unexpected and serious toxicity encountered in this trial. Eur J Cardiothorac Surg, 1993, 7(1), 50 - 1 Aspergillus prosthetic valve endocarditis; Stavridis GT et al.; A 66-year-old man developed Aspergillus fumigatus endocarditis, complicated by an aortic root abscess 9 months after his aortic valve replacement with a Carpentier Edwards xenograft . The aortic root was replaced with an antibiotic-treated fresh homograft and anti-fungal chemotherapy commenced 24 hours later . One month after this he developed a retrosternal pseudo-aneurysm of the ascending aorta . At re-operation the homograft was heavily infected with fungal growths and the patient was considered inoperable . This case is an example of a rare condition complicating cardiac valve prosthesis which still has a very poor prognosis, despite any surgical and chemotherapeutic efforts. Antimicrob Agents Chemother, 1993 Jan, 37(1), 54 - 9 Pharmacokinetics and protein binding of ceftriaxone during pregnancy; Bourget P et al.; The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy . Nine pregnant women (ages, 20 to 34 years) whose gestational ages ranged from 28 4/7 to 40 5/7 weeks were included . The diagnosis of infection was established in all cases; i.e., four women had chorioamnionitis and five women had pyelonephritis . The following triple antibiotic therapy was infused with the aim of achieving cure: CTX, 2 g once every 24 h (constant rate over 60 min); tobramycin, 3 mg/kg of body weight once every 24 h; and ornidazole, 1 g/day . Two series of blood samples were collected, i.e., during the first day of treatment (on day 1), to establish the primary pharmacokinetic profile of CTX, and at the plateau (on day 7), to evaluate a possible accumulation of the drug . This was an open, noncompartmental study, with each patient serving as her own control . Concentrations of total and unbound CTX in serum were measured by a high-performance liquid chromatographic method . Pharmacokinetic analysis was done by a noncompartmental method . Data were compared by a Wilcoxon t test (a P value of < or = 0.05 was considered significant) . Data were also compared with those obtained for healthy subjects who received similar treatments . (i) The tolerance to treatment was excellent, and in all cases patients had a complete remission without premature delivery . (ii) No accumulation of CTX was noted during the treatment, and the profiles of the drug determined at days 1 and 7 were not significantly different.(iii) The pharmacokinetic parameters measured in pregnant patients during the third trimester of pregnancy were similar to those measured in healthy subjects . (iv) Residual concentrations of total and unbound CTX measured at 24 h were greater than the MICs for allegedly susceptible organisms, both on day 1 and at steady state . (v) During the final 3 months of pregnancy, the dosage schedule of CTX (2-g infusion per day) required no particular adjustment (i.e., neither a loading dose nor any increase in the maintenance dose.) Skeletal Radiol, 1993, 22(1), 17 - 23 CT evaluation of primary epiphyseal bone abscesses; Azouz EM et al.; We reviewed the clinical, radiographic, and computed tomographic (CT) findings in eight children with a histologically proven diagnosis of epiphyseal or apophyseal osteomyelitis . In all cases the femur was involved: in five the osteomyelitis was localized in the femoral condyle, in two it was in the greater trochanter, and in one it was in the femoral head epiphysis . In four of the six cases of epiphyseal involvement there was associated joint effusion or septic arthritis . CT examination may demonstrate a serpentine tract, a sequestrum, cortical destruction or adjacent soft tissue swelling and can differentiate osteomyelitis from other epiphyseal lucent lesions, particularly chondroblastoma and osteoid osteoma . CT yielded important new diagnostic information in seven of the eight patients, failing to do so in only one . In one case, CT showed a wooden splinter in an abscess cavity, which had been mistaken for a sequestrum . When combined with accurate clinical and laboratory information and good quality plain radiographs, CT can lead to an early diagnosis of epiphyseal infection . Early diagnosis helps avoid delays in initiating antibiotic or surgical treatment caused by the unusual (epiphyseal or apophyseal) location of the bone abscess. Int J STD AIDS, 1993 Jan-Feb, 4(1), 21 - 5 Factors associated with trichomoniasis, candidiasis and bacterial vaginosis; Hart G; Of 6125 women attending an STD clinic from 1988 to 1991, 5365 (88%) were tested for vaginitis of whom 97 (1.8%) had trichomoniasis, 945 (17.6%) had candidiasis, 734 (13.7%) had bacterial vaginosis and 3628 (67.6%) were free of vaginal infection . Dual infections occurred in 49 (0.9%) patients . Independent predictors for trichomoniasis by multivariate analysis were being pregnant (odds ratio (OR) = 2.4), having vaginal discharge or dysuria (OR = 4.7), being Aboriginal (OR = 4.3), being Asian (OR = 5.0), being unemployed (OR = 2.1) or tattoed (OR = 1.9) . Many factors, including use of oral contraception (OR = 1.2) and current antibiotic medication (OR = 1.5), had a small significant association with candidiasis . Independent predictors for bacterial vaginosis were having multiple sex partners in the past month (OR = 1.6), being unmarried (OR = 1.5), being unemployed (OR = 1.3) being a prostitute (OR = 1.5) and not currently using antibiotic medication (OR = 2.5) . The epidemiological profiles were consistent with trichomoniasis and bacterial vaginosis being sexually transmitted diseases with epidemiology different from that of gonorrhoea and chlamydia and different from each other, and candidiasis being a disease in which constitutional factors are more important than issues relating to sexual transmission. Bol Med Hosp Infant Mex, 1993 Jan, 50(1), 7 - 16 {The verbal autopsy on children with a respiratory infection and acute diarrhea . An analysis of the disease-care-death process}; Reyes H et al.; The study focuses on children between 72 hours and five years of age who died of acute respiratory infection (ARI) or acute diarrhea (AD) in the State of Tlaxcala . Peer Review Mortality Committee of the State contributed with the staff to the deaths analysis . Cases were included only when diagnosis was confirmed by verbal autopsy (VA) . One hundred and thirty two cases were included (98 corresponding to ARI deaths and 34 to AD) . The process related to medical care-seeking behaviors and prescribing practices by private and non-private physicians was analyzed through the VA . During the study period, 60% of children with ARI and 58.9% of children with AD died at home . More than 80% of these children had received medical care within three days preceding their death, and 50% of them had been seen by a physician within 12 hours prior to their death . Most of these visits were to a private doctor (71% for ARI and 86% for AD) . Forty seven percent of treatments prescribed for ARI were judged to be wrong, either because of a bad choice of antibiotic or because the physician did not prescribe an antibiotic when the patient required it . Similarly, 65% of treatments for AD were considered erroneous, either due to the use of an antibiotic which was not justified or due to the lack of oral rehydration therapy when it was needed . Additionally, late referral to a hospital was considered as having direct influence at the death in half of the consultation . Families were too late in demanding medical care or demanded no care at all in 21.9% of cases of ARI and in 6.1% of cases of AD . We have found the VA to be useful in identifying problems related to the process of health-seeking behaviors and medical care . Our results suggest interventions that may lower the high mortality rates in Tlaxcala, such as training workshops directed to institutional and private physicians, and the implementation of top-of-line treatment centers where high-risk patients can be referred and also the health care workers can learn the correct treatment of both diseases . Future studies should focus on the identification of alarm signs and risk factors that may help to lower mortality due to ARI or AD, when recognized and treated at early stages. Mol Biochem Parasitol, 1993 Jan, 57(1), 117 - 26 Stable integration and expression of the Plasmodium falciparum circumsporozoite protein coding sequence in mycobacteria; Haeseleer F et al.; The DNA coding for the circumsporozoite protein of Plasmodium falciparum (CSP; aa 1-412) has been placed under the control of the mycobacterial promoter derived from the gene encoding the 64-kDa antigen of Mycobacterium bovis-BCG . This expression cassette was cloned into pJRD184, an Escherichia coli multicloning site vector, together with the kanamycin resistance gene from Tn903 and the attachment site and integrase gene from the temperate mycobacteriophage FRAT1 . One of the resulting plasmids, pNIV2173, introduced by electroporation into both Mycobacterium smegmatis and M . bovis-BCG, integrated at a specific site in the genome of each recipient . Recombinants expressed immunoreactive polypeptides, ranging in size from 62 to 43 kDa, at a level of about 1% of total soluble proteins . Part of this material was present in the culture medium indicating that mycobacterial recombinants were able to secrete the CSP . The M . smegmatis and M . bovis-BCG recombinants, transformed with pNIV2173 and grown in absence of antibiotic, were followed for more than 400 and 50 generations respectively . Over this time span, neither DNA rearrangement nor loss of expression was observed . Inoculation of the recombinant BCG to mice did not induce humoral response to CSP nor proliferative response to CSP Th2R CD4+ T lymphocyte epitope. J Periodontol, 1993 Jan, 64(1), 1 - 15 The role of metronidazole in the treatment of periodontal diseases; Greenstein G; This article discusses the ability of metronidazole to improve periodontal health . Review of the drug's pharmacology and potential side effects indicate that it poses little threat to humans of inducing acute toxicity, mutagenesis, or cancer if used according to recommended dosing regimens . Studies addressing metronidazole utilization in a variety of clinical conditions demonstrate that its routine use does not enhance root planing . However, adjunctive antibiotic therapy may be advantageous in the treatment of sites where effective root planing is precluded due to deep pockets or when anaerobic periodontal infections do not respond to conventional therapy. Int J Dermatol, 1993 Jan, 32(1), 65 - 7 Treatment of rosacea: topical clindamycin versus oral tetracycline; Wilkin JK et al.; BACKGROUND . A new topical antibiotic preparation, clindamycin in a lotion base, was compared with oral tetracycline in the treatment of rosacea . Forty-three patients clinically diagnosed as having rosacea were examined in an investigator-blinded study . METHODS . Patients used topical clindamycin lotion applied twice daily or the usual oral dose of tetracycline hydrochloride (250 mg four times a day for 3 weeks, then 250 mg twice a day for the remaining 9 weeks) . Patients' lesions were examined clinically at 3-week intervals over a period of 12 weeks . RESULTS . Topical clindamycin treatment produced similar clinical results to oral tetracycline and was superior in the eradication of pustules . CONCLUSIONS . These results show topical clindamycin in a lotion base to be a safe and effective alternative to oral tetracycline therapy in the treatment of rosacea. Clin Orthop, 1993 Jan, (286), 289 - 97 The effect of wound environment on the incidence of acute osteomyelitis; Evans RP et al.; A model was developed to identify and compare the local wound factors that induce acute osteomyelitis in a prospective, controlled investigation . When compared with wounds containing either virulent bacteria or dead bone, statistical analysis disclosed a significant increase in the incidence of osteomyelitis when virulent bacteria and dead bone were combined . The incidence of osteomyelitis in wounds containing an inoculated, hematoma-filled dead space was significantly less when compared with wounds containing dead bone and virulent bacteria . The incidence of osteomyelitis is significantly less when a nonvirulent strain of bacteria is substituted for a virulent strain . Although rigid internal fixation increased the incidence of osteomyelitis to 100% and long-term antibiotic therapy decreased the incidence, these changes were not statistically significant . These data allow the authors to predict the relative risk of osteomyelitis when these wound factors are present . The prevention of osteomyelitis depends on the clinical identification and modification of these local wound factors. J Manipulative Physiol Ther, 1993 Jan, 16(1), 43 - 6 Osteomyelitis of the femur head in a pediatric patient; Pokras R et al.; A case of posttraumatic osteomyelitis of the femur head is discussed . This article emphasizes the importance of radiographic examination in posttraumatic cases . We describe the common radiographic appearance of osteomyelitis, and then the appropriate mode of treatment for the patient via antibiotic therapy and surgical debridement/curettage. Dis Mon, 1993 Jan, 39(1), 1 - 52 Cystic fibrosis; Aitken ML et al.; Cystic fibrosis, an autosomal recessive disorder, is the most common genetic disease of Caucasians . One in 25 Caucasians are carriers of the gene . The gene is found far less commonly in other races . There are over 230 different alleles of the gene, located on the 7th chromosome . The gene encodes for a membrane protein that functions as an ion channel . The survival of cystic fibrosis patients has been gradually increasing, with a mean survival in 1990 of 28 years . If the current trend of improved survival continues, it is estimated that half of cystic fibrosis patients will be over 18 years old by 1996 . Disease is found in many organs including the lungs, sinuses, pancreas, gastrointestinal tract, hepatobiliary system, sweat glands and reproductive tract . The majority of patients die of pulmonary disease . The airways become chronically colonized with bacteria that cannot be eradicated, leading to bronchitis, bronchiectasis, and finally, pulmonary fibrosis with respiratory failure . The pulmonary disease may be complicated by massive hemoptysis and pneumothorax . Patient survival rates have increased because of antibiotic therapy and improved nutrition with pancreatic enzyme replacements . New treatments for the pulmonary disease are under clinical trial and include antiproteases, amiloride, a sodium channel blocker, and DNase . The insertion of the normal cystic fibrosis allele into an animal model using a modified adenovirus with effective transcription suggests that gene therapy may be possible in the future, but safety and technical problems have to be addressed. Clin Nucl Med, 1993 Jan, 18(1), 35 - 9 Clinical and prognostic effect of a positive granulocyte scan in infective endocarditis; Borst U et al.; Thirty patients with clinical signs of infective endocarditis and pathologic echocardiographic findings indicating vegetations underwent scanning with In-111 or Tc-99m hexamethylpropylene amineoxime (HMPAO) labeled granulocytes . Blood cultures were positive in 60% of the patients . The other cases were negative as a result of antibiotic pretreatment . The results of scintigraphy were correlated with the subsequent clinical course, and in 20 cases with data obtained by histologic examination of the valves . With regard to the degree of the inflammatory process, the nuclear medical procedure provided the following results: true-positive in 6 cases, false-positive in 1 case, true-negative in 19 cases, and false-negative in 3 cases . In this study, positive granulocyte scans correlate with high activity of the inflammatory process and predict a poor prognosis for the patients concerned. Neurosurgery, 1993 Jan, 32(1), 45 - 9; discussion 49-50 Monitoring of infectious intracranial aneurysms by sequential computed tomographic/magnetic resonance imaging studies; Ahmadi J et al.; To monitor the course of infectious intracranial aneurysms, repeated cerebral angiography has been recommended every 2 weeks during intravenous antibiotic therapy until the aneurysm has resolved or an operation has been performed . However, serial cerebral angiograms are not without some risk to the patient . We have prospectively studied five patients harboring a total of six infectious intracranial aneurysms by sequential computed tomography (CT) and/or magnetic resonance imaging (MRI) studies . All infectious aneurysms were initially identified by cerebral angiography and were treated with 6 to 8 weeks of intravenous antibiotics . The aneurysm size ranged from 4 to 10 mm . Sequential CT scans and/or MRI studies were obtained at 2- to 3-week intervals to monitor the course of the aneurysms . Three aneurysms enlarged during antibiotic therapy, and one remained unchanged in size . These four aneurysms were treated surgically . The two remaining aneurysms resolved with intravenous antibiotic therapy . Cerebral angiograms were obtained routinely preoperatively and were used to verify the resolution of the infectious aneurysms when they were no longer visible on CT or MRI . On the basis of this prospective study, we conclude that sequential thin-slice CT and/or MRI can effectively and safely monitor the course of infectious intracranial aneurysms once identified by cerebral angiography . This may reduce the need for serial angiography and reduce the ultimate risk in the management of infectious intracranial aneurysms. Life Sci, 1993, 52(4), PL25 - 30 Anti-allergic activity of roxithromycin: inhibition of interleukin-5 production from mouse T lymphocytes; Konno S et al.; This study was designed to evaluate the effects of roxithromycin (RXM), a newly synthesized macrolide antibiotic on allergic responses in mice . RXM was orally administered into BALB/c mice once a day for 42 days in a single dose of 5 mg/kg body weight . Spleen cells (Sp C) collected from mice on day 7, 14, 28 and 42 post-RXM administration showed higher blastic activity of lymphocytes than those from control . The activity peaked on the 7th day, then gradually decreased, and returned to the control level by the 42nd day . Production of cytokines, IL-2 and IL-5, by Sp C in response to concanavalin A stimulation was also examined in the course of RXM administration . The capacity of Sp C to produce IL-2 was enhanced by oral administration of RXM for 28 days . However, a long-term (for 42 days) administration inhibited it . On the other hand, the capacity of of Sp C to produce IL-5 was strongly inhibited by oral administration of RXM; the titer of IL-5 was similar to that obtained in cultures of Sp C from control mice . These results strongly suggest that oral administration of RXM inhibits the function of Th2-type helper T lymphocytes and that a long-term administration of RXM may be beneficial in asthma and allergy. J Bone Joint Surg Br, 1993 Jan, 75(1), 28 - 31 Exchange arthroplasty for infected knee replacements . A new two-stage method; Scott IR et al.; We report a series of 17 exchange arthroplasties for infected knee prostheses, ten one-stage and seven two-stage procedures . The method proved successful in controlling infection and restoring function . In two-stage exchanges the interval between the stages was managed by using a prosthesis as a spacer, and acrylic cement beads containing the appropriate antibiotic to provide high local concentrations . Three one-stage procedures had recurrence of infection, but were successfully treated by further exchange operations . All patients had satisfactory function and there have been no serious complications . We recommend this modified two-stage technique for the management of infected knee arthroplasties. Ann Otol Rhinol Laryngol, 1993 Jan, 102(1 Pt 1), 11 - 5 Kikuchi-Fujimoto disease of the neck . Update; Garcia CE et al.; Kikuchi-Fujimoto disease (KFD) is a rare entity of uncertain cause that commonly presents with persistently enlarged cervical lymph nodes unresponsive to antibiotic therapy . Although it usually follows a benign course, KFD has been repeatedly misdiagnosed as malignant lymphoma; hence, clinicians and pathologists alike need to be aware of this disease entity . The newest developments regarding the etiology and course of KFD are presented through a review of the literature and a recent illustrative case. Environ Mol Mutagen, 1993, 21(1), 67 - 72 Elevation of sister chromatid exchange frequency in transformed human fibroblasts following exposure to widely used aminoglycosides; McDaniel LD et al.; Aminoglycosides are a class of antibiotics that interfere with protein translation . Geneticin and hygromycin are two such agents, which have been shown to exhibit highly toxic effects in mammalian cells . Cloned bacterial genes, which inactivate these antibiotics, have facilitated the establishment of dominant selection systems, which are widely used in eukaryotic molecular genetics . We have examined the effect of aminoglycosides on the sister chromatid exchange (SCE) frequency in transformed human fibroblast cell lines . Geneticin and hygromycin were both found to increase SCE frequency in all cell lines examined, including a cell line derived from a patient with Bloom syndrome, a disorder exhibiting an elevated spontaneous SCE frequency . Induction was seen to occur in a dose-responsive manner and was also observed in cells expressing the resistance genes that inactivate the cellular toxicity of these antibiotics . The implications of these findings for somatic cell genetics and for human gene therapy protocols are discussed. J Am Coll Cardiol, 1993 Jan, 21(1), 1 - 5 Percutaneous balloon pericardiotomy for the treatment of cardiac tamponade and large pericardial effusions: description of technique and report of the first 50 cases; Ziskind AA et al.; OBJECTIVES . This study describes the technique, clinical characteristics and results of the first 50 patients undergoing percutaneous balloon pericardiotomy as part of a multicenter registry . BACKGROUND . Percutaneous balloon pericardiotomy involves the use of a percutaneous balloon dilating catheter to create a nonsurgical pericardial window . METHODS . Patients eligible for percutaneous balloon pericardiotomy had either cardiac tamponade (n = 36) or a moderate to large pericardial effusion (n = 14) . In addition to clinical follow-up, serial echocardiograms and chest X-ray films were obtained . RESULTS . The procedure was considered successful in 46 patients after a mean follow-up period of 3.6 +/- 3.3 months . Two patients required an early operation, one for bleeding from a pericardial vessel and one for persistent pericardial catheter drainage . Two patients required a late operation for recurrent tamponade . Minor complications of the procedure included fever in 6 of the first 37 patients (studied before the prophylactic use of antibiotic agents), thoracentesis or chest tube placement in 8 and a small spontaneously resolving pneumothorax in 2 . Despite the short-term success of this procedure, the long-term prognosis of the 44 patients with malignant pericardial disease remained poor (mean survival time 3.3 +/- 3.1 months) . CONCLUSIONS . Percutaneous balloon pericardiotomy is successful in helping to manage large pericardial effusions, particularly in patients with a malignant condition . It may become the preferred treatment to avoid a more invasive procedure for patients with pericardial effusion and a limited life expectancy. Khirurgiia (Sofiia), 1993, 46(1), 6 - 9 {The clinical use of lincomycin in treating anaerobic infection in patients with surgical abdomen}; Viiachki I et al.; Experience is recorded with lincomycin treatment of 59 patients with acute surgical abdomen . The primary anaerobic flora was eradicated in 86 per cent of the patients . For the very good therapeutic results essential was the early instituted adequate antibiotic therapy in adequate dose and for adequate length of time. Intensive Care Med, 1993, 19(5), 265 - 72 Importance of pre-existing co-morbidities for prognosis of septicemia in critically ill patients; Pittet D et al.; OBJECTIVE: To determine admission characteristics associated with the outcome of septicemia in critically ill patients and more specifically assess the prognostic value of pre-existing co-morbidities . DESIGN: 5 year-retrospective cohort study . SETTING: Surgical Intensive Care Unit (ICU-20 beds) in a 1600 bed-tertiary care center . PATIENTS: Among 5457 patients admitted to the ICU between 1984 and 1988, 176 (3.2%) met prospectively-defined criteria for blood culture-proven septicemia (8.77 per 1000 patient-days) . Overall septicemic patients had a 5-fold increased risk of death compared to non-septicemic patients (relative risk 5.03, 95% confidence intervals 4.17-6.07, p < 0.0001), and this estimate persisted after stratification according to age, sex, primary diagnosis and conditions of admission to the ICU (emergency/elective) . RESULTS: Prognostic factors recorded on admission to ICU that were associated with mortality from septicemia among 173 patients were older age, higher admission Apache II score, gastrointestinal surgery, ultimately and rapidly fatal diseases and the number of co-morbidities in addition to the principal diagnosis (active smoking, alcohol abuse, non-cured malignancy, diabetes mellitus, splenectomy, recent antibiotic therapy, major surgery, or major cardiac event) . In the multivariate analysis with logistic regression procedures, Apache II and co-morbidities were identified as the two independent predictors of mortality . CONCLUSIONS: Pre-existing co-morbidities assessed at the admission to the ICU significantly improved the prediction of mortality from septicemia compared to Apache II score alone. Eur J Cancer, 1993, 29A Suppl 3, S14 - 7 Reduction of infection rates in cancer patients associated with the use of haematopoietic growth factors; Gerhartz HH; As the risk of infection associated with chemotherapy is related to the depth of the fall in neutrophil counts, protection from neutropenia has been used as an endpoint for growth factors in this setting . However, the functional status of these and other myeloid cells are also important . Therefore, more direct measurements of clinical improvement will also be useful . Several studies have suggested that the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) can result in improvements in hospital stay, days of fever, antibiotic use and thrombocytopenia . Similar findings have been confirmed by our own work which indicates that GM-CSF not only shortens the period of leukopenia, but also reduces the complications of infection . More sensitive and appropriate endpoints should be included in future trials, including rate of and survival from infection as well as overall and disease-free survival. Acta Med Austriaca, 1993, 20(3), 61 - 4 {After-care by the internal medicine physician following liver transplantation}; Vogel W et al.; Orthotopic liver transplantation offers the only therapeutic option for many patients with end-stage liver disease . In adults, the overall five-year survival following transplantation has increased dramatically from approximately 30% a decade ago to nearly 70% currently . Cyclosporine A became available in the 1970s and substantially improved immunosuppressive therapy . It is now the mainstay of the therapeutic approach to prevent graft rejection . The postoperative care of liver transplant recipients is one of the most exciting challenges in clinical medicine . On the basis of the experience and results of the Innsbruck liver transplant programme the management of liver transplant recipients will be discussed with regard to the typical time frame of complications . We present data of 87 liver transplantations in 84 patients during a 10-year observation period . At present, intraoperative mortality is fortunately close to zero . Most of the deaths occur in the immediate postoperative period . Major complications are haemorrhage, hepatic artery or portal vein thrombosis, biliary leakage or graft dysfunction . In addition, side-effects resulting from high-dose immunosuppressive therapy or from antibiotic and antiviral therapy add to problems in this early period . Opportunistic infections, chronic graft failure, disease recurrence and nephrotoxicity related to Cyclosporine A therapy are complications seen during long-term management of liver transplant patients . The differential diagnosis and the adequate management of these complications are a great challenge to every hepatologist. Life Sci, 1993, 53(1), 77 - 84 Tylosin inhibits the steroidogenesis in mouse Leydig cells "in vitro"; Meisel ML et al.; Former investigations in rats revealed effects of tylosin on the pituitary gonadal axis . After 15 days treatment the animals showed reduced weights of the seminal vesicles, increased pituitary weights, diminished LH/FSH stores in the pituitary and reduced peripheral levels of LH . To investigate if, in addition, the antibiotic exerts a direct effect on the steroidogenesis, the reactivity of Leydig cells was determined: a) after 8 days pretreatment of the donor mice in vivo; b) after addition of the antibiotic in vitro; c) after addition of the antibiotic in vitro in presence of dibutyryl cyclic AMP or hydrocholesterol . Tylosin caused an inhibition of basal and stimulated testosterone production, all the same if it was applied in vivo or in vitro . Moreover the increase in testosterone production caused by dibutyryl cyclic AMP was inhibited as well as that caused by addition of hydrocholesterol . These data give rise to the suspicion that tylosin inhibits directly intracellular steps of testosterone biosynthesis of Leydig cells. Arch Virol, 1993, 129(1-4), 317 - 25 Mapping of the functional domains of the alpha 4 protein of herpes simplex virus 1; Sivropoulou A et al.; Truncated alpha 4 genes were introduced into BHK tk- cells along with the neomycin phosphotransferase gene, that confers resistance to the eukaryotic antibiotic G418, driven by the HSV-1 beta tk promoter (beta tk- neor) . Stably transformed cell lines were obtained and studied for the ability of the resident truncated alpha 4 genes to regulate the expression of the beta tk- neor, and for the ability of the truncated alpha 4 polypeptides to localize to the nuclei of transformed cells . The results indicated that the domain(s) for beta gene induction and for nuclear localization of the alpha 4 protein are located within the N-terminal 288 amino acids of the protein. Ophthal Plast Reconstr Surg, 1993, 9(1), 51 - 2 Acute dacryocystitis secondary to exudative rhinitis; Goldberg SH et al.; This report describes the unusual occurrence of acute dacryocystitis secondary to exudative rhinitis . An 18-year-old man with no prior history of tearing or dacryocystitis presented with acute left dacryocystitis . Nasal mucosal edema, lymphoid hyperplasia, and exudate obstructed the ostium of his left nasolacrimal duct . The patient improved rapidly with systemic antibiotic and nasal decongestant drugs . Both the nasolacrimal duct obstruction and dacryocystitis resolved completely within 2 weeks . One year later, serology suggested Epstein-Barr virus as the cause of the rhinitis . Acute intranasal inflammation may obstruct the nasolacrimal duct with potential secondary dacryocystitis . This type of nasolacrimal duct obstruction resolves without sequelae when the rhinitis improves. Scand J Infect Dis, 1993, 25(3), 395 - 7 Nasal administration of IgA to individuals with hypogammaglobulinemia; Lindberg K et al.; Many immunodeficient patients constantly carry non-typable Hemophilus influenzae (NTHI) in the nasopharynx, despite seemingly adequate antibiotic therapy . We have studied the effect of nasal administration of IgA on nasopharyngeal colonization in 5 patients with hypogammaglobulinemia, with a productive cough, especially in the mornings, who were constant carriers of NTHI in the nasopharynx, and had IgA, 1 ml 6 times/day, given nasally for 14 days . Nasopharyngeal cultures were obtained on days 0, 7, 14 and 28 . Two of the patients became culture-negative during the treatment, and the cough was alleviated in all patients. Adverse Drug React Toxicol Rev, 1993 Summer, 12(2), 83 - 95 Chloramphenicol toxicity; Holt D et al.; Although high serum concentrations of chloramphenicol are related to toxicity, as shown experimentally and during treatment, the mechanism of toxicity remains unclear . Published work suggests that relatively minor metabolites may be causally related to toxic reactions in vitro and some of these metabolites have been detected in sera from treated patients . It is possible that all the major toxic manifestations of chloramphenicol may be explained by attack by free radicals . Depletion in compounds acting as cellular antioxidants, such as glutathione and vitamin E, may conceivably increase the vulnerability of an individual to chloramphenicol toxicity, while supplementation with an antioxidant might protect against it . Research into the metabolism of chloramphenicol and into the mechanism of its toxicity has declined since early work in the 1950s and 1960s, but its continuing use worldwide means that there is justification for renewed interest in the toxicology of this useful antibiotic. Int J Clin Pharmacol Res, 1993, 13(2), 69 - 73 Effects of some cephalosporins and teicoplanin on platelet aggregation; Cazzola M et al.; Antibiotics may interfere with platelet (PLT) function, and beta-lactam antibiotics may interact with PLT aggregation, by inhibiting the binding of agonists of this aggregation (such as ADP and collagen) to specific receptor sites . In this study we have evaluated the relative in-vitro antiplatelet effects of some old and new cephalosporins (cefonicid, ceftazidime, ceftriaxone, cefotaxime, cefuroxime and flomoxef) and of teicoplanin, a new glycopeptide antibiotic . All the cephalosporins tested, and also teicoplanin, were found to have the potential to adversely affect human platelet aggregation only at high concentrations which are not achieved in vivo. Scand J Plast Reconstr Surg Hand Surg, 1993, 27(2), 143 - 7 Dermatome shaving of psoriasis . Seven years experience in 112 patients; Momsen OH et al.; Data from the records of 112 patients who were treated by dermatome shaving for psoriasis vulgaris were analysed . A psoriatic "area" was defined as all psoriatic skin lesions present in a specific region at the first treatment, and 108 patients with 202 areas were included in the study . In 68 patients the treatment was limited to a single area, and 40 patients had from two to nine areas treated, mainly on the legs and arms . Complications occurred in nine patients; one had a wound infection that required treatment with an antibiotic, in five patients healing was prolonged, and three patients developed unsightly scars . Thirty-seven patients and 104 areas have not recurred during mean follow-up periods of 1.4 years and 1.9 years, respectively . In all 108 patients the median recurrence free period was eight months (range: 0-5.6 years) . The median recurrence free period for the 202 areas was 13 months (range: 0-8.2 years) . Reshaving of partial recurrences in 46 patients led to 40% that did not recur . The best prognostic factor available is to do a test shave before initiating more extensive treatment. Int Ophthalmol Clin, 1993 Winter, 33(1), 9 - 22 The ocular manifestations of Lyme disease; Zaidman GW; Lyme disease (with its ocular manifestations) is a worldwide disorder that is rapidly increasing in frequency . It is a treatable, multisystemic disease that presents in three stages of severity . It can present with unusual forms of conjunctivitis, keratitis, cranial nerve palsies, optic nerve disease, uveitis, vitritis, and other forms of posterior segment inflammatory disease . A patient with any of these ocular manifestations should be questioned for exposure to an area endemic for Lyme disease, tick bites, skin rash, or arthritis . Such patients should undergo serological testing . If the clinical presentation is suggestive of Lyme disease, a course of oral antibiotics should be used (unless the patient gives a history of adequate therapy) . Topical corticosteroids can be used for anterior segment inflammation . An antibiotic therapeutic trial can be used for posterior segment or neuroophthalmic disease . Systemic corticosteroids without concomitant antibiotics should not be used in the treatment of ocular Lyme disease . If ocular Lyme disease is discovered and treated early, response to therapy is usually satisfactory. Trop Gastroenterol, 1993 Jan-Mar, 14(1), 28 - 32 Pancreatic abscess: is there a role for conservative therapy? Dasarathy S, Buch P, Saraya A, Acharya SK, Tandon RK. Pancreatic abscess is a serious complication of acute pancreatitis and non-operative management has been reported to carry a mortality of nearly 100% . We present five patients with pancreatic abscess, who were successfully treated with antibiotics alone . All 5 patients had acute pancreatitis followed by prolonged fever and development of an abdominal mass . The diagnosis was confirmed in each of them by a contrast enhanced CT scan and an ultrasound guided aspiration of pus from the pancreatic mass . The choice of antibiotics was decided by the culture reports in two cases and by Gram's staining in the remaining three patients . We attribute the success of antibiotic therapy in our patients to early diagnosis by CT scan and guided aspiration as well as the absence of any unfavourable risk factors . This study suggests that a select group of patients with pancreatic abscess may be managed conservatively with antibiotics. Bone Marrow Transplant, 1993, 11 Suppl 2, 12 - 22 The clinical consequences of haematological and non-haematological toxicity following bone marrow transplantation and the possible impact of haematopoietic growth factors; Maraninchi D; Bone marrow transplantation (BMT) is a rescue therapy used in conjunction with high-dose chemotherapy, which is an effective treatment for overcoming resistant disease in selected malignancies . However, highly intensive preparative regimens produce severe life-threatening toxicity which may be haematological or non-haematological . Despite extensive supportive care including isolation, empiric antibiotic use and parenteral nutrition, toxicity is associated with a significant level of morbidity and mortality . A major cause of morbidity is infection resulting from the period of neutropenia caused by the ablation of the patient's marrow . The haematopoietic growth factors (HGFs) may provide effective therapy for improving haematopoietic reconstitution and therapy decrease the risk of infection, days of hospitalisation and subsequently reducing overall treatment cost . They may also be useful for enhancing neutrophil function, improving bone marrow yield and mobilising peripheral blood progenitor cells (PBPC) . Recombinant G-CSF or GM-CSF may, therefore, improve the safety of the BMT procedure and increase its application to a greater number of patients. Ann Chir Gynaecol Suppl, 1993, 205, 1 - 52 Postoperative candidiasis; Rantala A; Candida species are important opportunistic pathogens in compromised hosts, such as patients recovering from major abdominal surgery . The incidence, pathogenesis, diagnosis and prognosis of postoperative candidiasis were studied in a general surgical department . Transplantation surgery was not included . The mean incidence of postoperative candidiasis in abdominal surgery was 6.2 per 1000 laparotomies . The estimated incidence was higher during the years 1987-1992 than 1981-1986 . Postoperative candidiasis was most often encountered in patients undergoing surgery of the small intestine or pancreas . These patients had certain typical features: a long hospitalization before signs, central catheterization, parenteral nutrition, prolonged antibiotic therapy and reoperations; malignancy, corticosteroid or immunosuppressive therapy were uncommon . Multiple blood cultures during reoperations were not found to yield Candida; hence, hematogenous dissemination from the gut was not seen . The prognosis of postoperative candidiasis was poor: the infection mortality was 70-79% and significantly higher than in patients with postoperative bacterial septicemia . Early therapeutic measures resulted in a significantly better prognosis as compared to delayed treatment . Arabinitol was found a specific marker of candidiasis, but because sequential samples were needed for adequate sensitivity, a single arabinitol concentration determination in the beginning of the disease was not useful . Febrile patients who had Candida in any sample during the first postoperative week had a poor prognosis . The results show that patients with candidiasis have typical clinical features that facilitate suspicion . Antifungal therapy is mandatory and must be started as soon as a suspicion of candidiasis has risen, before the results of specific laboratory tests are available. Curr Med Res Opin, 1993, 13(2), 109 - 18 Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy; Bucci L et al.; Fifty-eight patients, 30 males and 28 females, aged between 42 and 60 years (mean age 57 years) suffering from cirrhosis of the liver with signs and symptoms of portosystemic encephalopathy were studied . The double-blind study was performed according to a double-dummy experimental design, comparing the antibiotic rifaximin, administered at a dose of 1200 mg/day, with lactulose, administered at a dose of 30 g/day, both for 15 days . At the end of the treatment with the two drugs, there was a significant improvement in the main symptoms of portosystemic encephalopathy (mental state, asterixis, 'A' cancellation test, Reitan test) . The improvement, which was also confirmed by a reduction in the overall score attributed to the degree of portosystemic encephalopathy was undoubtedly correlated with the reduction in the levels of serum ammonia concentrations, recorded after only 3 days of treatment . Tolerability of the treatment with rifaximin was decidedly higher with respect to lactulose . The greater rapidity of action and the lack of side-effects with rifaximin recommend the use of this intestinal antibiotic in patients with medium to severe portosystemic encephalopathy. Ann Otolaryngol Chir Cervicofac, 1993, 110(1), 50 - 4 {Value of hyperbaric oxygen therapy in the treatment of malignant otitis externa . Apropos of a case}; Gilain L et al.; The authors report the case of a 75 years old insulin dependent diabetic man presenting a malignant otitis externa with facial nerve paralysis . Despite prolonged, adequate parenteral antibiotic therapy, the patient's clinical status did not improve . The addition of hyperbaric oxygen as a complementary treatment was followed by the regression of clinical signs and the resolution of infection . Based upon a review of the literature, the authors discuss the indications for this therapy and the problems involved in defining the criteria of cure in malignant otitis externa. Bull Pan Am Health Organ, 1993, 27(4), 382 - 8 Typhoid fever in rural Haiti; Olle-Goig JE et al.; A review was made of the clinical characteristics and evolution of all patients over 14 years old with typhoid fever who were treated at the Albert Schweitzer Hospital in Haiti from January 1989 through July 1991 . Two hundred and seventeen patients were studied . Their most common symptoms were fever (100%), diarrhea (64.1%), and abdominal pain (51.2%) . Splenomegaly and hepatomegaly were rarely noted . Sixty-eight patients (31.3%) were lost to follow-up, 129 (59.4%) were cured, and 20 (9.2%) died . There was a tendency for patients who were ill longer before seeking medical assistance to experience higher mortality . The data also indicate that patients with central nervous system involvement had a less favorable prognosis than other patients . Overall, the high incidence of hospital-reported cases (74 cases per 100,000 inhabitants) shown by these and other data makes it clear that typhoid fever is a highly prevalent infection in rural Haiti . At present, it appears that the only hope for effectively controlling the disease is by educating the population at risk, not only to prevent the disease but also to seek early medical assistance after becoming infected . Typhoid fever patients with a long history of illness before consultation may have a less favorable prognosis than other patients and should be kept under close observation . In addition, any suspected typhoid fever patient with signs of central nervous system involvement should be treated promptly with high-dose steroids, besides receiving an adequate antibiotic regimen. Ann Fr Anesth Reanim, 1993, 12(5), 469 - 73 {Intraosseous infusions in pediatric life-threatening emergencies}; Salino D et al.; As the bone marrow is a vascular tissue which cannot collapse, it may be used as a vascular access to treat life-threatening emergencies especially in children . Two cases reported here underline the value of this life-saving procedure . Both children were 9 months old, and were admitted for severe dehydration, having lost 15 and 10% of body weight respectively . All attempts to set up an intravenous infusion in a peripheral vein failed in both . The fontanelles were closed, and the central veins (internal jugular and subclavian veins) easily accessible, however collapsed . Intraosseous infusion was decided as a last ditch procedure . A 15-gauge Mallarme's trocar was inserted at the proximal end of the tibia . In both children, this allowed rehydration to be carried out, and, in the second child, anticonvulsive and antibiotic therapy to be started . The intraosseous line was replaced, in the first child, at the third hour, by a conventional infusion line, set up by denudation, and in the second one, by a subclavian line . This technique has few contra-indications, and the complication rate is low . However, this technique should remain limited to a few indications only. Med Dosw Mikrobiol, 1993, 45(2), 173 - 6 {Analysis of susceptibility of bacteria isolated from clinical material to cefuroxime, ceftazidime and cefotaxime}; Giedrys-Kalemba S et al.; The authors have compared the susceptibility of bacterial strains isolated from clinical material in 1990 and 1991 to the most frequently used cephalosporins: cefuroxime, ceftazidime and cefotaxime . The highest susceptibility in 1990 was to cefotaxime, which was seldom used at that time, unlike cefuroxime and ceftazidime . In 1991 an increase in the number of strains resistant to cefotaxime was found, in parallel with a further rise in resistance to cefuroxime and ceftazidime . Frequent use of an antibiotic in a certain region favours the development of resistance . This observation calls for rational therapy with antibiotics, supported by regular studies of susceptibility of the strains in the region. Zentralbl Chir, 1993, 118(11), 637 - 45 {Osteomyelitis today--diagnostic imaging and therapy}; Peters KM et al.; Plain radiography, bone scan and especially in infants sonography belong to the primary imaging methods for posttraumatic osteomyelitis . For further diagnostic check up of osteomyelitis CT, MRI and leukocyte scintigraphy are excellent methods . Treatment of posttraumatic osteomyelitis is today a combination of operation, local and systemic antibiotic therapy. Parasitol Res, 1993, 79(8), 683 - 9 Characterization of sinefungin-resistant Leishmania donovani promastigotes; Phelouzat MA et al.; Promastigotes resistant to sinefungin (SF), a nucleoside antibiotic that is structurally related to S-adenosylmethionine (AdoMet), were obtained starting from two cloned strains of Leishmania donovani . The resistance was induced by increasing the drug pressure gradually until promastigotes capable of growing in the presence of concentrations 10,000 times higher than the 50% growth-inhibitory (IC50) values for the control cells were obtained . The resistance to SF of both clones was specific and stable in the absence of drug pressure . High-performance liquid chromatographic (HPLC) analyses indicated highly reduced levels of SF in the two resistant clones . However, the intracellular SF concentration in these resistant cells was much higher than the IC50 values for wild-type cells . In one clone, the decreased drug uptake was coupled to a decrease in the affinity of two protein methylases for SF, whereas in the other clone the biosynthesis of polyamine precursors was modified . This study demonstrates that resistance to a drug molecule with pleiotropic targets can be developed through various mechanisms by different strains. J Postgrad Med, 1993 Jan-Mar, 39(1), 38 - 9 Bilateral otogenic cerebellar abscesses; Nadkarni TD et al.; An unusual presentation of bilateral otogenic cerebellar abscesses observed in two of our patients is reported . Both gave a history of otorrhoea, fever, headache, vomiting and had bilateral cerebellar signs and conductive hearing loss . The abscesses were detected on computerised tomography . X-rays revealed bilateral mastoiditis . The therapy followed was excision of abscesses, mastoidectomy and antibiotic therapy. Toxicol Pathol, 1993, 21(4), 369 - 76 Multinucleated hepatocytes induced by rifabutin in rats; Scampini G et al.; Rifabutin is an antibiotic of the rifamycin class, which is particularly active against mycobacteria, including those that occur in AIDS patients . Because clinical use will include long-term therapy, an extensive battery of long-term toxicity studies was carried out by the oral route, including carcinogenicity studies . An interesting feature was the occurrence of multinucleated hepatocytes (MNHs) in the rat . In some instances, as many as 25 nuclei occurred in a single cell . Light microscopy revealed a large hepatocyte with normal eosinophilic staining . The multiple nuclei stained like those present in the surrounding normal cells . Electron microscopy showed no abnormalities of the nuclei and no cell membranes within the cytoplasm . The customary organelles were present . MNHs were dose- and sex-related, starting from 10 mg/kg/day and being more evident in males . They began to appear after 5 wk of treatment and persisted over long periods of recovery (12 mo), without showing any tendency for cell proliferation . The life-span of MNHs was similar to that of normal hepatocytes . MNHs were present in the carcinogenicity study, but there was no increase in liver tumors . MNHs did not occur in mice or monkeys treated with rifabutin, nor did they occur in response to treatment with rifampin . The effect appears to be specific to the rat. Rev Laryngol Otol Rhinol (Bord), 1993, 114(2), 129 - 33 {Application of osseous allografts in surgery of the middle ear . Authors' experience}; Soushko YA et al.; The authors describe an osseous allograft enabling reconstruction with or without filling of the middle ear cavities in suppurative chronic otitis . This filling material is a cryoconserved osseous allograft . It is saturated with an antibiotic sensitive to the germs responsible for otorrhea based on the data of the antibiotic sensitivity test and is thus adapted to each patient . The technique for preparing the material is described . This material was applied to 70 patients, including some who received the material over four years ago . The operation made it possible to stop the infection . The long-term check-ups show good tolerance of the material with, nevertheless, a certain amount of resorption in some cases. Langenbecks Arch Chir, 1993, 378(6), 335 - 8 {Results of surgical therapy of bacterial sacroiliitis with primary arthrodesis}; Schubert T et al.; Surgical treatment of pyogenic infections of the sacroiliac joint is indicated in cases of ineffective conservative treatment, abscess formation, septicemia, and neurological deficits . Between 1983 and 1990 in nine patients surgical treatment was performed for pyogenic sacroiliitis under this criteria . The surgical procedure included joint debridement, primary arthrodesis of the sacroiliac joint using a autologous bone graft, antibiotic therapy and postoperative immobilisation . Follow-up examination of 8 patients in average 47 months postoperatively revealed excellent functional and roentgenological results in 6 patients . Two patients suffered only from mild low-back pain, none of the eight patients demonstrated signs of a recurrent infection, one patient died due to complications of a long-lasting preoperative septicemia . Regarding these postoperative follow-up results surgical therapy including primary sacroiliac arthrodesis should be early considered, because this treatment has a low complication rate and the surgical technique is easy to perform and results are excellent or good in most of the patients. J Fr Ophtalmol, 1993, 16(8-9), 446 - 52 {Value of corticoids in the treatment of postoperative endophthalmitis}; Auclin F et al.; Postoperative endophthalmitis, which has a dreadful reputation, needs early and aggressive treatment . Apart local and systemic antibiotic therapy, the place of corticosteroid treatment is still discussed . The authors retrospectively compared three groups of patients treated with appropriate antibiotics but with different corticosteroid . Group I received high dose corticosteroids early regimen, group II received delayed corticosteroids treatment and group III did not receive corticosteroids . Visual recovery as well as vitreous transparency better in group I. Glas Srp Akad Nauka {Med}, 1993, (43), 257 - 62 {Modern therapy of Lyme disease}; Bojic I et al.; The treatment of Lyme disease is placed in the centre of more than one medical discipline . So far the efficacy of antibiotic therapy application showed various results . The results of the treatment of two groups of the patients with Lyme disease were presented in the paper . The first group of twenty two patients was treated three weeks by the regime I, and the second group of nine patients was treated eight weeks by the regime II . During 3-year follow up 50% of the patients from the first group and 22% of the patients from the second group had recurrences . The total number of the recurrences in the second group was eight times less than the total number of the recurrences in the first one . The application of antibiotic therapy in the treatment of Lyme disease during eight weeks and more can contribute to the falling number of recurrences. Glas Srp Akad Nauka {Med}, 1993, (43), 237 - 9 {Lyme carditis--case report}; Joksimovic Z et al.; A patient with Lyme-disease manifested by circulatory disorders of complete AV block and ventricle disorder of rhythm was presented . Besides cardiologic symptoms during the period of illness, transitory skin and neurologic symptoms appeared . The patient has not been treated by antibiotic therapy and after a year no late symptoms of illness appeared. Glas Srp Akad Nauka {Med}, 1993, (43), 233 - 6 {Rhombencephalitis as a manifestation of neuroborreliosis}; Pavlovic D et al.; Rhombencephalitis is a rare neurological manifestation of stage II of Lyme disease . We presented two cases with no recollection of tick bite nor erythema migrans and with cranial nerve nuclei, pyramidal tract and cerebellar tracts involvement of sudden onset, inflammatory syndrome in cerebrospinal liquor, positive oligoclonal bands and elevated IgG index . A spontaneous remission occurred in both cases, but antibiotic was given intravenously for prevention of relapses and disease progression. Glas Srp Akad Nauka {Med}, 1993, (43), 203 - 12 {The clinical picture of Lyme disease in neurology}; Pavlovic D et al.; Neuroborreliosis of central and peripheral nervous system was found in 24 patients with typical and atypical clinical syndromes . Information about tick bite was obtained in only 1/3 of our patients . Specific antibodies were found in 3/4 by flourescent antibody test, oligoclonal bands in 1/2, and signs of inflammation in cerebrospinal fluid in 1/3 of patients . The majority had favourable reaction to antibiotic therapy . It is necessary to investigate every case of suspected neuroborreliosis because it can imitate many neurological diseases . One must insist on information about the tick bite and/or erythema migrans and search for specific antibody production, both in blood and cerebrospinal fluid. Glas Srp Akad Nauka {Med}, 1993, (43), 161 - 7 {Lyme disease in children and adolescents}; Grubisic S et al.; 148 children and adolescents with Lyme borreliosis and tick bite or suspection on tick bite were examined . The examined patients were aged from 14 months to 24 years and divided into four age groups . Skin lesions were discovered in 25 percent of patients with tick bite . Erythema migrans occurred in 91 percent, Lymphocytoma in 3 percent and sclerodermatous lesions (Lichen sclerosus et atrophicus and Morphea) in 6 percent of patients with Lyme disease . Serologic tests on the presence of antibodies to Borreliae burgdorferi were performed in 96 percent of cases with tick bite . Antibody titer 1:80 or higher in 8 percent of patients with tick bite, was discovered . We found positive serologic test results in 5 (29 percent) of 29 persons with Erythema migrans, in 4 (4 percent) of 110 patients with tick bite (without skin lesions), as well as, in 1 patient with Lymphocytoma . Antibiotic therapy was applied in all cases with Erythema migrans, in person with Lymphocytoma, as well as, in patients with asymptomatic infections (patients without skin lesion recalling a tick bite and with antibodies against Borrelia burgdorferi) . A general sensitivity, to infection with Borrelia burgdorferi, is stressed, a fact based on appearance by Lyme borreliosis in all age groups even in the newborn children. Oncol Res, 1993, 5(3), 133 - 8 A comparison of the effects of aphidicolin and other inhibitors on topoisomerase II-directed cytotoxic drugs; Haldane A et al.; We have compared the effects of a number of inhibitors including aphidicolin, 2,4-dinitrophenol (DNP) and novobiocin on the in vitro cytotoxicity of several topoisomerase II (topo II)-directed agents, using cultured murine Lewis lung carcinoma cells . These agents comprised amsacrine, CI-921 (9-{(2-methoxy-4-methylsulfonylamino)phenylamino}-N,5-dimethyl-4- acridinecarboxamide isethionate, isethionate, a derivative of amsacrine), DACA (N-{2-(dimethylamino)ethyl}acridine-4-carboxamide dihydrochloride, a new DNA intercalator with high solid tumor activity), daunorubicin, doxorubicin, epirubicin, etoposide, mitoxantrone, and teniposide . Novobiocin, an antibiotic that affects topo II action, reduced the cytotoxic effect of DACA as well as that of amsacrine and doxorubicin, and reduced the extent of G2-phase arrest by DACA . DNP, an uncoupler of mitochondrial respiration, inhibited drug action in a manner similar to that of novobiocin but to a smaller extent . Aphidicolin, a specific inhibitor of DNA polymerase-alpha, reduced the cytotoxic effect of amsacrine, CI-921, etoposide, and teniposide but not that of DACA, daunorubicin, doxorubicin, epirubicin, or mitoxantrone . The immediate effect of each topo II-directed agent on the incorporation of thymidine into DNA was also measured at a drug concentration (D10) that killed 90% of cells . Susceptibility to aphidicolin reversal was strongly correlated with inhibition of thymidine incorporation (r = 0.91; p < or = 0.001) . The results suggest that the involvement of DNA replication in the cytotoxic action of topo II-directed agents differs according to the agent used. Surg Gynecol Obstet, 1993, 177 Suppl, 50 - 4; discussion 65-70 Risk of infection, infecting flora and treatment considerations in penetrating abdominal trauma; Nichols RL et al.; Infectious complications postoperatively for penetrating abdominal trauma are a major cause of morbidity, which contributes significantly to increased length of hospitalization stay and the cost of patient care . The results of recent studies have suggested that the probability of a major infection after traumatic intestinal perforation of the individual patient can be predicted from risk factors noted at the time of the operation . The factor most closely associated with the development of infection is peritoneal contamination by intestinal contents . Other significant risk factors (p < 0.05) are the number of organs injured, number of units of blood administered, ostomy formation for left colonic injury and patient age . The risk of patients being infected can be predicted and thereby used to guide postoperative treatment decisions . Adjusting trauma care choices in antibiotics, duration of antibiotic administration and incisional wound management could result in significant savings . Standard operative procedures, the use of parenteral antibiotics (the duration of which has been one to two days in most recent studies) effective against endogenous aerobic and anaerobic organisms and leaving the surgical incision open decrease the incidence of postoperative wound infection . Despite such preventive measures, major infection remains a problem. Surg Gynecol Obstet, 1993, 177 Suppl, 41 - 9; discussion 65-70 Postoperative pneumonia in the intensive care unit; Fry DE; Postoperative pneumonia in the surgical patient may occur from atelectasis and inadequate postoperative TV, from ventilator-associated pathophysiology and from aspiration . Each process ultimately elicits the proinflammatory responses from the lung in the effort to eradicate the infectious pathogens . Postoperative pneumonia is best prevented by maintaining a clear understanding of the biologic basis for infection in the lung . Therapy requires aggressive tracheobronchial drainage strategies and antibiotic therapy directed toward the pathogens that are producing the pulmonary inflammatory response. Surg Oncol, 1993, 2(1), 1 - 6 Retroviral gene transduction of circulating progenitor cells in patients with metastatic breast cancer; Coles RE et al.; The use of somatic gene therapy for the treatment of breast cancer has many potential applications . Because chemotherapeutic protocols for breast cancer are commonly limited by bone marrow toxicity, transduction of genes into pleuripotent stem cells may allow the generation and maintenance of immune responses in the presence of lymphocytotoxic agents . The practical utility of stem cell isolation and transduction would be enhanced if stem cells circulating in the peripheral blood could be isolated in patients, however this approach has been limited by the small numbers of such cells in the circulation . In these studies, recombinant granulocyte colony stimulating factor (G-CSF) was administered to patients with metastatic breast cancer to increase the number of circulating stem cells . Stem cells in the peripheral blood were then isolated and a retroviral vector (LXSN) was used to transduce the neomycin phosphotransferase gene into these cells . Gene transduction was demonstrated by resistance to the toxic effects of a neomycin analog (G418) and the detection of retroviral DNA from transduced cells . A practical method of transfer of exogenous genes into the circulating pleuripotent stem cells of patients with metastatic breast cancer is documented by these experiments . Application of these findings may allow the generation of cells resistant to anti-neoplastic agents or unique lymphoid effector cells with potent immune functions for the treatment of patients with metastatic breast cancer. Akush Ginekol (Mosk), 1993, (4), 40 - 2 {The immunocorrective therapy of cervix uteri diseases}; Zemskov AM et al.; Analyzes the results of comprehensive clinical and immunologic examinations of women with inflammatory and tumorous diseases of the cervix uteri . Demonstrates a reduction of the immunologic reactions in such diseases and in traditional antibiotic therapy thereof . Presents methods of immunocorrective therapy with vitamin E, thymactin, and sodium nucleinate to be carried out on an inpatient basis. Neuroradiology, 1993, 35(7), 529 - 31 Lyme disease presenting as a stroke in the vertebrobasilar territory: MRI; Defer G et al.; A 28-year-old female farmer, without vascular risk factors, developed a limited infarct of the pons, associated with a lymphocytic cerebrospinal fluid (CSF) pleocytosis . Titres of specific antibodies against Borrelia burgdorferi were high in serum and CSF . MRI confirmed an infarct in the territory of the medial pontine arteries, but angiography showed no evidence of cerebral angiopathy . Antibiotic therapy rapidly led to a return to normal of CSF cytology and serology . We suggest that Lyme disease is a possible cause of cerebral ischaemia. J Clin Apheresis, 1993, 8(2), 78 - 81 Treatment of babesiosis by red blood cell exchange in an HIV-positive, splenectomized patient; Machtinger L et al.; Babesiosis is a malaria-like parasitic disease causing subclinical or mild illness in most cases . Splenectomized patients, however, may experience a more severe course . Although generally responsive to antibiotic therapy, several cases of severe babesiosis refractory to appropriate antibiotic therapy have been reported to respond promptly and dramatically to red blood cell (RBC) exchange transfusion . Although the role of HIV coinfection in babesiosis is uncertain, two previously reported cases raise a concern that it may predispose to a more severe clinical course . We report a third case of severe babesiosis in an HIV-positive splenectomized man, following travel to an endemic area . Antibiotic therapy, though initially effective, ultimately failed to prevent severe disease . RBC exchange transfusion resulted in prompt clinical improvement, which has been sustained during 26 months of follow-up . Although the patient has since developed various sequelae of HIV infection, including disseminated Kaposi's sarcoma, CMV retinitis, and enteritis, there has been no recurrence of observable parasitemia . In severe babesiosis, RBC exchange transfusion, combined with appropriate antibiotic therapy, appears to be a rapidly effective therapeutic modality which can induce sustained remissions. Free Radic Res Commun, 1993, 19(2), 81 - 92 The role of glutathione in protection against DNA damage induced by rifamycin SV and copper(II) ions; Saez GT et al.; Incubation of calf thymus DNA in the presence of rifamycin SV induces a decrease in the absorbance of DNA at 260 nm . The effect, was found to be proportional to the antibiotic concentration and enhanced by copper(II) ions . In the presence of rifamycin SV and copper(II), a significant increase in thiobarbituric acid-reactive (TBA-reactive) material is also observed . This effect is inhibited to different degrees by the following antioxidants: catalase 77%; thiourea 72%; glutathione (GSH) 62%; ethanol 52%; and DMSO 34%, suggesting that both hydrogen peroxide (H2O2) and hydroxyl radicals (OH.) are involved in DNA damage . Rifamycin SV-copper(II) mixtures were also found to induce the production of peroxidation material from deoxyribose and, in this case, glutathione and ethanol were the most effective antioxidant substrates with inhibition rates of 91% and 88% respectively . Electrophoretic studies show that calf thymus DNA becomes damaged after 20 min . incubation in the presence of both agents together and that the damaged fragments run with migration rates similar to those obtained by the metal chelating agent 1,10-phenanthroline . Normal DNA electrophoretic pattern was found to be preserved by catalase, and GSH at physiological concentrations and by thiourea . No protection is observed in the presence of ethanol or DMSO . The results obtained indicate the involvement of different reactive species in the degradation process of DNA due to rifamycin SV-copper(II) complex and emphasize the role of reduced glutathione as an oxygen free radical scavenger. Eye, 1993, 7 ( Pt 3), 468 - 71 No eye pad for corneal abrasion; Kirkpatrick JN et al.; We have carried out a randomised clinical trial to assess the healing rate and level of discomfort experienced in two groups of patients with simple traumatic corneal abrasions . Patients treated with antibiotic ointment and mydriatic alone have a significantly improved healing rate compared with those treated with antibiotic ointment, mydriatic and a double eye pad with bandage (0.05 > p > 0.02) . There was no significant difference in the level of discomfort experienced by the two groups. Rev Assoc Med Bras, 1993 Jan-Mar, 39(1), 12