Rev Prat, 1999 May 1, 49(9), 971 - 5 {Therapeutic prospects for subacute transmissible spongiform encephalopathies}; Seman M et al.; There is currently no effective therapy available for Creutzfeldt-Jakob disease . However, a limited number of drugs such as polyanions, the amyloid-binding dye Congo red, amphotericin B and anthracyclines have been found to delay the appearance of the clinical signs in experimental prion diseases . Today, the most promising agent appears to be less toxic derivative the amphotericin B, MS-8209 . Indeed this compound has a wide spectrum of anti-prion activity and constitute the unique molecule able to prolong survival time when treatment is performed at the late stages of infection . This result represents an important progress in therapeutical approaches of prion diseases and justify the development of new polyene antibiotic derivatives. Thromb Res, 2002 Jan 1, 105(1), 49 - 53 Recurrent pulmonary embolism in a 13-year-old male homozygous for the prothrombin G20210A mutation combined with protein S deficiency and increased lipoprotein (a); Kosch A et al.; We report the case of a 13-year-old male presenting with recurrent symptoms of respiratory distress after a trauma of the lower limb . Pulmonary symptoms had been misinterpreted for several weeks and only marked symptoms of deep venous (DVT) and caval vein thrombosis later prompted the correct diagnosis of DVT and embolic events and subsequently a successful thrombolytic therapy . The case reported here shows a diagnostic pitfall of pulmonary embolism in an adolescent . It emphasizes the need to consider the possibility of thromboembolic events also in young children and adolescents presenting with atypical pulmonary symptoms and suffering from pulmonary diseases not responding to antibiotic therapy . In addition, although the homozygous PT A20210A gene mutation is a rare defect and its relevance as a risk factor on its own remains to be elucidated, this case suggests that a complete thrombophilia laboratory workup should be performed in young patients with a first symptomatic thromboembolic onset. Clin Microbiol Infect, 1997 Apr, 3(2), 187 - 191 Chlamydia pneumoniae: a new opportunistic infectious agent in AIDS? Monno R, Leone E, Maggi P, Buccoliero G, Valenza MA, Angarano G. OBJECTIVE: To determine the incidence of Chlamydia pneumoniae respiratory tract infection in HIV-positive or AIDS patients . METHODS: Serum samples from 82 HIV-positive patients with fever and respiratory symptoms were evaluated using microimmunofluorescence assay to detect C . pneumoniae-specific IgG and IgM antibodies . RESULTS: Twenty patients were found to have IgG antibodies to C . pneumoniae at titers ranging between 1:16 and 1:1024 . Seven of the patients had evidence of acute C . pneumoniae infection (a fourfold rise in the titer of IgG antibody, or a single IgG titer of greater-than-or-equal1:512, or a single IgM titer greater-than-or-equal1:16) . Five were diagnosed as having pneumonia and two bronchitis . No co-infection with other respiratory tract pathogens was found . CONCLUSIONS: Results of this study indicate that C . pneumoniae may play a role in the etiology of respiratory tract infections in HIV-positive patients; this fact should affect empirical antibiotic prescription. Cornea, 2002 Mar, 21(2), 164 - 8 N-acetylcysteine in chronic blepharitis; Yalcin E et al.; PURPOSE: To investigate the effects of N-acetylcysteine (NAC) in chronic posterior blepharitis . METHODS: This was a prospective randomized, controlled study that included 79 eyes of 40 patients with chronic posterior blepharitis . Routine ophthalmologic examination, Schirmer-1 test, fluorescein break-up time (FBUT), and mucous fern tests were carried out during the first visit of all patients . A topical steroid, topical antibiotic, and artificial tears were started in 36 eyes of 18 patients . The therapy group (43 eyes of 22 patients) was administered three daily doses of 100 mg oral NAC . All patients were examined weekly for 1 to 4 months (average, 24 +/- 0.7) . A Schirmer-1 test and FBUT were administered at every visit, but mucous fern tests were administered every two weeks . The results of the first and last Schirmer-1 tests, FBUT, and mucous fern test were compared between the therapy and control groups . Student's t and Mann-Whitney U tests were used for statistical analysis . RESULTS: FBUT was significantly increased (p < 0.0001), and the mucous fern pattern was also significantly improved (p = 0.0096) in the therapy group . CONCLUSION: NAC is thought to increase FBUT and improve mucous fern pattern by blocking lipid peroxidation in chronic blepharitis. J Pharmacol Exp Ther, 2002 Mar, 300(3), 862 - 7 Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure; Pacher P et al.; Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) by oxidant-mediated DNA damage is an important pathway of cell dysfunction and tissue injury in conditions associated with oxidative stress . Increased oxidative stress is a major factor implicated in the cardiotoxicity of doxorubicin (DOX), a widely used antitumor anthracycline antibiotic . Thus, we hypothesized that the activation of PARP may contribute to the DOX-induced cardiotoxicity . Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ34, we now demonstrate the role of PARP in the development of cardiac dysfunction induced by DOX . PARP-1+/+ and PARP-1-/- mice received a single injection of DOX (25 mg/kg i.p) . Five days after DOX administration, left ventricular performance was significantly depressed in PARP-1+/+ mice, but only to a smaller extent in PARP-1-/- ones . Similar experiments were conducted in BALB/c mice treated with PJ34 or vehicle . Treatment with a PJ34 significantly improved cardiac dysfunction and increased the survival of the animals . In addition PJ34 significantly reduced the DOX-induced increase in the serum lactate dehydrogenase and creatine kinase activities but not metalloproteinase activation in the heart . Thus, PARP activation contributes to the cardiotoxicity of DOX . PARP inhibitors may exert protective effects against the development of severe cardiac complications associated with the DOX treatment. Front Biosci, 2002 Mar 01, 7, e66 - 76 Chlamydia pneumoniae as a respiratory pathogen; Hahn DL et al.; Chlamydia pneumoniae is a recently recognized human respiratory pathogen with a unique biphasic life cycle characterized by an obligate intracellular (replicative) and an extracellular (infectious) form of the organism . C . pneumoniae is widely distributed and, via the respiratory route, infects the majority of the world's population . The majority (70%) of acute human C . pneumoniae respiratory tract infections are asymptomatic or only mildly symptomatic but a minority (30%) cause more severe respiratory illnesses including community-acquired pneumonia, bronchitis and a variety of upper airway illnesses . After acute infection the C . pneumoniae intracellular life cycle is characterized by the development of metabolically inert (and thus antibiotic resistant) atypical "persistent" inclusions; this biologic behavior correlates with a clinical course following acute symptomatic illness that is characterized by persistence of symptoms that are difficult to treat with antibiotics . A role for C . pneumoniae in chronic respiratory illness is currently under investigation: "persistent" intracellular inclusions contain increased quantities of chlamydial heat shock protein 60 (hsp 60), a highly immunogenic protein that has been implicated in the pathogenesis of established chronic inflammatory chlamydial diseases (blinding trachoma, pelvic inflammatory disease and tubal infertility) . An emerging body of evidence, including host immune response to chlamydial hsp 60, links C . pneumoniae infection with a spectrum of chronic inflammatory lung diseases of currently unknown etiology (asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD)) . Further laboratory developments, including reliable and practical diagnostic methods and antibiotics effective against persistent infection, will be required to recognize and treat acute C . pneumoniae infection, and to advance our knowledge and understanding of the role of chronic infection in asthma, chronic bronchitis and COPD. Prog Urol, 2001 Dec, 11(6), 1274 - 6 {Pseudotumoral xanthogranulomatous pyelonephritis: diagnosis with percutaneous biopsy and success of conservative treatment}; Reul O et al.; Focal xanthogranulomatous pyelonephritis is an unusual form of chronic renal infection that is difficult to diagnose prior to surgery . We report on a 19-year-old woman who presented with a renal mass that mimicked malignancy . The diagnosis of focal xanthogranulomatous pyelonephritis was first suspected by radiological findings and further confirmed by histopathologic examination of percutaneous biopsy specimens of the lesion . Successful treatment of the patient was achieved with antibiotic therapy alone . Maximal efforts, including percutaneous renal biopsy, should be made to establish the diagnosis of focal xanthogranulomatous pyelonephritis before a therapeutic decision is reached . We recommend the use of antibiotics as a first-line treatment for patients with focal xanthogranulomatous pyelonephritis. J Immunol, 2002 Mar 1, 168(5), 2383 - 92 IL-10 is critical for host resistance and survival during gastrointestinal helminth infection; Schopf LR et al.; Resistance to many intestinal nematodes is dependent on the induction of polarized type 2 cytokine responses, whereas type 1 responses can exacerbate these infections . The contributions of IL-4 and IL-13 to the development of resistance have been well described for a variety of intestinal parasites; however, the role of IL-10 has not been previously investigated . In this study we infected IL-10-, IL-10/IL-4-, IL-10/IL-12-, IL-4-, and IL-12-deficient mice with Trichuris muris to determine whether IL-10 contributes to the development of immunity . Interestingly, T . muris-infected IL-10-, IL-4-, and IL-10/IL-4-deficient mice failed to expel the parasite, and animals deficient in IL-10 displayed marked morbidity and mortality . In contrast, double IL-10/IL-12-deficient mice were completely resistant and mounted a highly polarized type 2 cytokine response, demonstrating that the increased susceptibility of IL-10-deficient mice was dependent on IL-12 . Further study suggested that the susceptibility of IL-10- and IL-10/IL-4-deficient mice was probably attributable to a marked increase in type 1 cytokine production in those animals . The mortality observed in T . muris-infected IL-10- and IL-10/IL-4-deficient mice correlated with increased inflammation, loss of Paneth cells, and absence of mucus in the cecum . Interestingly, survival was enhanced in T . muris-infected IL-10/IL-4-deficient mice if a broad spectrum antibiotic was administered, suggesting that an outgrowth of opportunistic bacteria was contributing to the high degree of morbidity and mortality . Overall, these studies reveal a critical role for IL-10 in the polarization of Th2 responses, development of resistance during T . muris infection, and maintenance of barrier function in the colon. Foot Ankle Int, 2002 Feb, 23(2), 130 - 4 Single stage correction with external fixation of the ulcerated foot in individuals with Charcot neuroarthropathy; Farber DC et al.; The ulcerated foot in individuals with Charcot neuroarthropathy presents a complex problem when correction of the deformity is necessary but the presence of infection precludes the use of internal fixation . We reviewed 11 patients with midfoot Charcot neuroarthropathy, collapse, and ulceration who were at risk for amputation . These patients underwent operative debridement, corrective osteotomy, external skeletal fixation and culture-directed antibiotic therapy as a limb salvage procedure . Patients were transitioned from the external fixator (average 57 days) to total contact casting (average 131 days) and all subsequently progressed to therapeutic footwear in 12 to 49 months of follow-up (average 24 months), except one patient whose medical decline resulted in bedrest . We believe that when performed in properly selected patients, this procedure presents an alternative to amputation and, via corrective osteotomy, results in a shoe-able, functional foot that is potentially less prone to ulceration. Clin Microbiol Infect, 1999 Apr, 5(4), 213 - 218 Pharmacokinetics of teicoplanin during plasma exchange; Alet P et al.; OBJECTIVE: To study the elimination of teicoplanin during plasma exchange, a procedure currently used to treat a variety of disorders involving immune complexes . Teicoplanin is a glycopeptide antibiotic that exhibits a long terminal half-life (100-150 h) and is highly bound to plasma proteins (unbound fraction (fu)=0.2) . METHODS: Twelve adults with systemic polyarteritis nodosa, cryoglobulinemia-induced vasculitis or dysglobulinemic neuropathy undergoing plasma exchange were studied . Each patient received intravenous teicoplanin, 6 mg/kg body weight, immediately before plasma exchange . Plasma was assayed for teicoplanin by high pressure liquid chromatography . RESULTS: A high level of protein binding of teicoplanin was measured within this patient population (98%) . The mean quantity of teicoplanin eliminated (+/-SD) was 74.6+/-34.6 mg . The mean drug fraction eliminated by plasma exchange (+/-SD) was 19.5+/-5.6% . Mean fu value as determined by ultrafiltration (+/-SD) was 2.2+/-1.7% . CONCLUSIONS: These results show that plasma exchange influences teicoplanin pharmacokinetics, with a clinically significant quantity being eliminated . If trough teicoplanin concentrations of around 10 mg/L are desired, it is recommended that teicoplanin dosage be supplemented or given after plasma exchange. J Surg Res, 2002 Mar, 103(1), 55 - 60 Local pharmaceutical release from a new hydrogel implant; Petratos PB et al.; BACKGROUND: Solid hydrogel polymers can act as reservoirs for controlled drug release . The object of this study was to quantify release kinetics for a single example of a class of uniquely structured hydrogels . The polymer of this study belongs to a class of permanent implants that release pharmaceuticals by diffusion from an entangled cross-linked matrix rather than by absorption of the implant by the body . The cross-linked matrix (CLM) of this study is biocompatible and polymerized in situ, forming a solid that is mechanically bonded to the implant site . It can seal tissue as well as deliver drugs at predetermined rates . We evaluated dye and antibiotic egress and assessed release kinetics and retention of antibiotic activity following elution from the CLM . MATERIALS AND METHODS: The prepolymerized test CLM was prepared in two ratios, 6 and 20% prepolymer, in an activating aqueous solution . Aqueous solutions were prepared from dyes of varying molecular weights . Aliquots of prepolymerized test CLM were allowed to solidify and dye release into the supernatant was quantified by spectrophotometry over a 168-h period . Antibiotic solutions were also employed to form solid CLMs . Tetracycline release over time was characterized by spectrophotometry . Antibiotic dosed solid CLMs were placed on agar plates streaked with Escherichia coli and incubated . Growth inhibition was assessed for each antibiotic . RESULTS: In the test CLM, dye and antibiotic release were found to be inversely related to molecular weight and consistent with a diffusion model . CLMs formed from aqueous solutions containing higher molecular weight dyes and antibiotics released those constituents more slowly than lower molecular weight constituents . This finding, as well as the effect on release rate under varying prepolymer concentration, was consistent with a diffusion release mechanism . Antibiotic released from the tissue sealant was shown to be potent by consistent inhibition of E . coli . CONCLUSIONS: Pharmaceutical release by a representative CLM was found to be controllable by varying the concentration of the pharmaceutical in the activating aqueous solution . The polymerization and release mechanisms did not degrade antibiotic biologic activity . CLMs may be a general class of biocompatible polymers that can locally deliver clinically useful biologics, the release kinetics of which are unaffected by the variability of implant absorption/inflammation mechanisms. Crit Care Nurs Clin North Am, 2000 Dec, 12(4), 477 - 87 Penetrating trauma to the head; Blank-Reid C et al.; Penetrating trauma to the brain is not as common as blunt trauma; however, the incidence is becoming a frequent occurrence in our society . Rapid transport to trauma centers where definitive care can be rendered is essential . Outcome depends on the site of the missile tract, the presenting neurologic status, and the extent of neurologic tissue destruction . Neurologic deterioration occurs rapidly, and outcome results seem to depend on the patient's neurologic status at the time of surgery . CT scanning is the diagnostic procedure of choice and should be performed if the patient's condition is stable (see Fig . 3) . Aggressive removal of missile and bone fragments needs to be balanced by the knowledge that it is preferable to leave behind a few hard-to-reach fragments than to increase the patient's neurologic deficit . CT scanning in the postoperative period is very helpful in identifying abscess formation as well as new or recurrent hematomas, edema, and areas of tissue injury not evident at the time of initial scanning . Antibiotic therapy should be initiated preoperatively . Control of elevated ICP plays a significant role in decreasing mortality and morbidity . Judicious debridement of injured brain combined with medical management of increased ICP will maximize the quality of recovery and increase survivability . Although great strides have been made in reducing mortality and morbidity for trauma patients, the sad issue is that the majority of traumas are preventable . Until society is willing to understand that it needs to make firearm safety a priority, there will always be patients to care for who have sustained a penetrating injury. Neurol Clin, 2001 Nov, 19(4), 867 - 85 Dementia; Volicer L et al.; Alzheimer's disease is the most common cause of dementia, but often several other conditions causing dementia are present on brain autopsies . Palliative care medical issues are similar in all late stage progressive degenerative dementias and include; cardiopulmonary resuscitation, transfer to acute care setting, antibiotic therapy, and tube feeding . Behavioral symptoms of dementia include agitation and resistiveness to care . Quality of life of individuals suffering from dementia is enhanced by availability of meaningful activities and by avoidance of restraints . Family support and involvement are crucial for optimal care . Formulation of advanced directives or an advance proxy plan is important for assuring the patient's previous wishes or best interests are considered when decisions about treatment strategies are made. Biochim Biophys Acta, 2002 Jan 30, 1542(1-3), 32 - 40 Novobiocin is a novel inducer of CD38 on cells of the myelomonocytic lineage; Thiele A et al.; KG-1a, HL-60 and U-937 cells, which represent different stages of myelopoiesis, showed growth retardation in response to the coumarin antibiotic novobiocin . Novobiocin was found to increase CD38 expression (in all three cell lines) and to induce differentiation along the monocytic path in HL-60 and U-937 cells but not in KG-1a cells . The increase in surface expression of CD38 was matched by NAD glycohydrolase activity and by increases in the level of specific mRNA, indicating that the gene product is active and that regulation occurs at the level of transcription or mRNA stability . Of the three cell lines tested, only the early KG-1a expressed N-cadherin, a member of Ca(2+)-dependent adhesion molecules involved in embryonic differentiation processes . In contrast to CD38, N-cadherin was slightly down-regulated pointing to a specific role of novobiocin in gene regulation. Zhonghua Yan Ke Za Zhi, 2000 Sep, 36(5), 355 - 7 {An analysis of bacterial culture results in infectious endophthalmitis}; Lu J et al.; OBJECTIVE: To study the changes of positive rate of bacterial culture of vitreous specimens from patients with infectious endophthalmitis during the past ten years and search for sensitive antibiotics for its treatment . METHODS: Vitreous specimens were taken from 304 eyes of 304 cases with clinically diagnosed infectious endophthalmitis for bacterial culture, and drug sensitivity test was carried out for the positive specimens . RESULTS: Bacterial positive rate was 53% with insignificant changes among the different years . Cefoperazone was the most sensitive antibiotic . CONCLUSION: Bacterial culture combined with drug sensitivity test of vitreous specimens is important in guiding the treatment of infectious endophthalmitis. Arch Dermatol, 1965 Aug, 92(2), 142 - 6 Allergy to lichens . Allergic contact dermatitis from usnic acid produced by lichenized fungi; Mitchell JC; Two forest workers affected with allergic contact dermatitis, which occurred only during work in forest areas, showed positive patch test reactions to lichens containing usnic acid and to isolated usnic acid . Lichens are plants composed of fungi living in symbiosis with algae . Usnic acid, one of the lichenic acids which accumulates in lichenized fungi, is a monobasic acid with dibenzofuran structure and antibiotic properties . Dibenzofuran is chemically related to furocoumarans . Lichens are plentiful in temperate zone forests and allergy to usnic acid represents some part of the "cedar-poisoning" problem in British Columbia . Geographical distribution of lichens containing usnic acid suggests that allergy to usnic acid will be found to be more common than presently recognized. Oncogene, 2002 Feb 14, 21(8), 1242 - 50 Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St . John's wort that acts by induction of apoptosis; Schempp CM et al.; Hyperforin is a plant derived antibiotic from St . John's wort . Here we describe a novel activity of hyperforin, namely its ability to inhibit the growth of tumour cells by induction of apoptosis . Hyperforin inhibited the growth of various human and rat tumour cell lines in vivo, with IC(50) values between 3-15 microM . Treatment of tumour cells with hyperforin resulted in a dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and apoptosis-specific morphological changes . In MT-450 mammary carcinoma cells hyperforin increased the activity of caspase-9 and caspase-3, and hyperforin-mediated apoptosis was blocked by the broad-range caspase inhibitor zVAD.fmk . When added to MT-450 cells, hyperforin, but not paclitaxel, induced a rapid loss of the mitochondrial transmembrane potential Deltapsi(m), and subsequent morphological changes such as homogenization and vacuolization of mitochondria . Monitoring of Deltapsi(m) revealed that the hyperforin-mediated mitochondrial permeability transition can not be prevented by zVAD.fmk . This indicates that mitochondrial permeabilization is a cause rather than a consequence of caspase activation . Moreover, hyperforin was capable of releasing cytochrome c from isolated mitochondria . These findings suggest that hyperforin activates a mitochondria-mediated apoptosis pathway . In vivo, hyperforin inhibited the growth of autologous MT-450 breast carcinoma in immunocompetent Wistar rats to a similar extent as the cytotoxic drug paclitaxel, without any signs of acute toxicity . Owing to the combination of significant antitumour activity, low toxicity in vivo and natural abundance of the compound, hyperforin holds the promise of being an interesting novel antineoplastic agent that deserves further laboratory and in vivo exploration. Bone Marrow Transplant, 2002 Jan, 29(2), 159 - 64 Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and filgrastim after myelosuppressive chemotherapy; Weaver CH et al.; Filgrastim alone and sequential sargramostim and filgrastim have been shown to be more effective than sargramostim alone in the mobilization of CD34(+) cells after myelosuppressive chemotherapy (MC) . We sought to compare costs and resource use associated with these regimens . Data were collected prospectively alongside a multicenter, randomized trial of filgrastim, sargramostim, and sequential sargramostim and filgrastim . Direct medical costs were calculated for inpatient and outpatient visits and procedures, including administration of growth factors and MC . We followed 156 patients for 30 days or until initiation of high-dose chemotherapy . The main outcome measures were resource use and costs of inpatient and outpatient visits, platelet and red blood cell transfusions, antibiotic use, and apheresis procedures . Hospital admissions, red blood cell transfusions, and use of i.v . antibiotics were significantly more common in the sargramostim group than in the other treatment arms . In univariate and multivariable analyses, total costs were higher for patients receiving sargramostim alone than for patients in the other groups . Mean costs in multivariable analysis for the filgrastim and sequential sargramostim and filgrastim arms were not significantly different . Filgrastim alone and sequential sargramostim and filgrastim are less costly than sargramostim alone after MC, as well as therapeutically more beneficial. Am J Ther, 1995 Jul, 2(7), 490 - 498 The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients; Bachmann K et al.; The effect of a standard regimen of the investigational macrolide antibiotic, dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients . Eight male volunteers participated after giving informed consent . CSA was administered in three single doses (15 mg kg(minus sign1) p.o . each) in each of three phases: (1) prior to a 14-day regimen of dirithromycin; (2) at the end of a 14-day regimen of dirithromycin (500 mg p.o . qAM); and (3) 2 weeks after the last dose of a 14-day regimen of dirithromycin . Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation . No significant differences among treatment (phase) means were detected (p < 0.05) . We conclude that a typical 14-day regimen of dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males . The effect of a standard regimen of dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients . Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of dirithromycin . Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during dirithromycin treatment, and the changes in normalized C(av) were comparable . Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during dirithromycin treatment . CSA oral clearance, CL/F(SS), decreased by 17% during dirithromycin treatment . C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during dirithromycin treatment but were not significantly different from those either before or after dirithromycin . The magnitude of the pharmacokinetic changes for CSA during dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring. J Neurosci, 2002 Feb 15, 22(4), 1218 - 27 Inhibition of caspases prevents ototoxic and ongoing hair cell death; Matsui JI et al.; Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known . Here we identify several important signaling events that regulate the death of vestibular hair cells . Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways . Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA . Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis . Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment . Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life . It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells . We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle . Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner . In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly . Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle. Antimicrob Agents Chemother, 2002 Mar, 46(3), 863 - 5 Mutator bacteria as a risk factor in treatment of infectious diseases; Giraud A et al.; We show in a gnotobiotic mouse model that, in addition to direct selection of antibiotic-resistant bacteria, some antibiotic treatments also select for mutator alleles . Because of these mutator alleles' high mutation rates, the initial treatment failure increases the probability of failures in subsequent treatments with other drugs. Acta Chir Orthop Traumatol Cech, 2001, 68(6), 363 - 8 {Repair of chondral defects of the knee using a combination of autologous chondrocytes and osteochondral allograft--an animal model . Part I: in vitro culture of autologous chondrocytes}; Bacenkova D et al.; PURPOSE OF THE STUDY: In the study we used in vitro cultivated autologous chondrocytes in combination with osteochondral allografts for the treatment of local defects of articular cartilage on the animal model (rabbit) . MATERIAL: Chondrocytes for in vitro cultivation were harvested by biopsy of articular cartilage of rabbit . For the monolayer cultivation we used Nutrient mix F 12 (Gibco BRL) with addition of Lascorbic acid (50 micrograms/ml, Sigma) and insulin-trasferin-selenium (A 6.26 micrograms/ml, Gibco BRL), 20% of fectal serum (Gibco BRL) and antibiotic antimycotic solution (Gibco BRL) . Cultivation of chondrocytes took place at 37 degrees in the atmosphere of 5% CO2 . Multiplied chondrocytes re-suspended in fibrin glue in combination with two osteochondral allografts were used for the reparation of artificial defect of the rabbit cartilage . METHODS: For the analysis of collagen type II in the cultivation medium we used the principle of salting out by 30% ammonium sulphate and subsequent pepsinization in an acid environment with a repeated salting out by means of 2M of NaCl . Precipitates were dissolved in 5.0 M of acetic acid and used for SDS PAGE and immunoblotting . As a detection system we used ECL (Amersham/Pharmacia Biotech) . RESULTS: The final average number of chondrocytes multiplied by monolayer cultivation was 1.10(5) . The presence of collagen of type II has proved the preservation of the original phenotype of chondrocytes during cultivation . DISCUSSION: Bioengineering use of cell and tissue cultivation provides new options of the treatment of defect of connective tissue . Transplantation of autologous chondrocytes in combination with osteochondral allografts is on the basis of our results obtained so far a promising therapy . CONCLUSION: The aim of our work was an ex vivo expansion of autologous chondrocytes for the purpose of cell transplantation. J Hum Lact, 2001 Feb, 17(1), 54 - 65 Use of anti-infective agents during lactation: Part 2--Aminoglycosides, macrolides, quinolones, sulfonamides, trimethoprim, tetracyclines, chloramphenicol, clindamycin, and metronidazole; Chin KG et al.; Because many antibiotics are excreted into breast milk, it can be difficult for a practitioner to choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant . This article is the second of a three-part series discussing the use of anti-infective agents during lactation . The authors review general information regarding use and common side effects for several classes of antibiotics . They also summarize information, including documented milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, in a table that can help practitioners choose antibiotics that may be considered safe to use in the lactating mother. J Hosp Infect, 2002 Feb, 50(2), 127 - 32 The use of adult isolation facilities in a UK infectious diseases unit; Barlow G et al.; The emergence and re-emergence of communicable infections, especially those due to antibiotic resistant nosocomial pathogens, is likely to increase the burden on the limited isolation facilities of the UK . It was our perception, however, that isolation beds are not always used optimally; with patients requiring isolation sometimes being housed in open-bay beds, whilst other non-communicable patients are unnecessarily isolated . The main aim of this study was to test this hypothesis in a regional infectious diseases (ID) unit . A secondary aim was to provide useful data in the development of guidelines for the admission of patients to the new Dundee ID unit . One-third of patients (32% of all patients and 34% of total bed days) admitted to an isolation room in the current Dundee ID unit over a four-month period, were found to have low-risk or non-communicable conditions . In addition, 21 patients initially considered an infection risk, used 102 bed days following resolution of their infection . Evidence for the presence of patients with 'alert' infections housed in the open-bay beds of other wards, whilst low-risk or non-communicable patients are unnecessarily exposed to isolation in the ID unit, is presented . The findings suggest suboptimal use of the current Tayside University Hospitals' isolation facilities . Given the likelihood of high demand for the isolation of patients in the new Dundee ID unit, it is vital that these facilities are used appropriately, thereby minimizing the risk of nosocomial infection transmission and the unnecessary isolation of low-risk patients . Exp Parasitol, 2001 Nov, 99(3), 141 - 7 Gene amplification in amphotericin B-resistant Leishmania tarentolae; Singh AK et al.; Two Leishmania tarentolae cells were selected step by step for resistance to the polyene antibiotic amphotericin B, a second-line drug against the parasite Leishmania . One of the mutants was cross-resistant to ketoconazole . DNA amplification was observed in both mutants . The amplicons were extrachromosomal circles and were derived from different chromosomes . In one mutant the circle was unusually stable as it remained within the cell despite numerous passages in the absence of the drug . A circumstantial link between the copy number of amplicons and the resistance levels was established . Gene transfection experiments indicated that the link between the locus amplified and the resistance levels was not straightforward and possibly several mutations act together to lead to amphotericin B resistance . Ann Endocrinol (Paris), 2001 Dec, 62(6), 525 - 8 {Obesity, diabetes mellitus, and gas gangrene: a major therapeutic challenge}; Rouquette-Vincenti I et al.; Soft tissue infections are uncommon but prognosis is severe (20 to 50%) . Management consists in surgical debridement, antibiotic therapy against anaerobic and aerobic bacteria, and appropriate intensive care . When available, hyperbaric oxygen therapy is an integral part of the treatment . We report the case of 56-year-old female patient with diabetes (150 kg) was hospitalized in our unit a few days after surgical treatment of a buttocks abscess for clinical signs of peripheral gas gangrene . Surgical exploration showed necrotizing soft tissue infection with fasciitis . Adequate therapy using antibiotics, surgery daily and hyperbaric oxygen was given . Therapy had to be adapted to the patient's obesity . Outcome was good with recovery and few sequelae, allowing transfer to a medical ward. Br J Haematol, 2001 Dec, 115(4), 817 - 25 Generation of reactive oxygen species is not involved in idarubicin-induced apoptosis in human leukaemic cells; Liu FT et al.; The anthracycline antibiotic idarubicin (IDA) induces double-stranded DNA breaks, the generation of reactive oxygen species (ROS) and apoptosis in human leukaemic cells . It is unclear whether the generation of ROS is associated with the apoptotic process . Using the T-lymphoblastic leukaemic CEM cell line, we found that IDA-induced DNA breaks were correlated with final cell death . The reduction in mitochondrial membrane potential (Deltapsim) and the generation of ROS occurred simultaneously with IDA-induced activation of caspase-9 and caspase-3 . Inhibition of caspases by a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk) completely blocked IDA-induced reduction of Deltapsim, apoptosis and final cell death . Interestingly, ROS generation was significantly enhanced by Z-VAD-fmk . ROS generation was neither caspase dependent nor part of the apoptotic process . IDA-mediated reduction in Deltapsim is caspase dependent and is not a consequence of the generation of ROS . These results indicate that IDA-induced generation of ROS and apoptosis are separate events . Inhibition of caspases facilitates IDA-mediated generation of ROS. Chemistry, 2002 Jan 18, 8(2), 439 - 50 Total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis; Mann S et al.; We describe the first synthesis of amiclenomycin, a natural product that has been found to inhibit biotin biosynthesis and, as a consequence, to exhibit antibiotic properties . Structure 1, with a trans relationship between the ring substituents . had previously been proposed for amiclenomycin on the basis of its 1H NMR spectrum . We have prepared the trans and cis isomers 1 and 2 by unequivocal routes and we conclude that the natural product is in fact the cis isomer 2 . The properly substituted cyclohexadienyl rings were constructed first . A cycloaddition reaction between 1,2-di(phenylsulfonyl)ethylene and the N-allyloxycarbonyl diene 13, followed by reductive elimination of the phenylsulfinyl groups, gave the cis isomer 15 . To obtain the trans isomer, the O-trimethylsilyl diene was used to give the cis hydroxylated Diels-Alder adduct 33, which was transformed into the corresponding trans amino derivative by means of a Mitsunobu reaction . The L-alpha-amino acid functionality was introduced by means of a Strecker reaction on the aldehydes 16 and 42, followed by enzymatic hydrolysis with immobilised pronase. Biopolymers, 2002, 67(1), 49 - 55 Circular dichroism study of interactions of Fungizone or AmBisome forms of amphotericin B with human low density lipoproteins; Barwicz J et al.; Amphotericin B (AmB), a potent antifungal agent used to treat invasive fungal infections, is still employed more than 40 years after its introduction in the pharmacopea . When injected into the blood stream, this antibiotic is carried by low density lipoproteins (LDLs) to which it induces the formation of oxidation products responsible in part for some of the severe adverse effects of the drug . However, the oxidative damages induced to LDLs are not yet understood . We present here the effects of the Fungizone and AmBisome forms of AmB on LDLs as compared to those of CuSO(4), a well-known powerful oxidant of LDLs . We use circular dichroism (CD) spectroscopy, which is particularly useful because it allows the investigation of the structural integrity of the proteic moiety of LDL upon interaction with AmB . The CD spectra also yield information on the drug itself because in its oligomer form it presents a strong dichroic signal in a spectral region different from that of the protein . Our results show that neither form of AmB changes the secondary structure of the protein while the helical content of the LDL is increased either in the presence of CuSO(4) alone or in the presence of CuSO(4) and AmBisome or Fungizone . On the other hand, the CD spectra of the antibiotic indicate that Fungizone AmB suffers important oxidative damage in the presence of LDLs and CuSO(4) while this damage is not present with AmBisome AmB . These observations lead us to propose that the structural modifications of the proteic part of LDLs induced by the Cu(2+) ions are involved in the important oxidative damage suffered by Fungizone AmB, which in this form is much more susceptible to interaction with its environment than AmBisome . Neurosurgery, 2002 Mar, 50(3), 437 - 48; discussion 438-9 Nonvestibular schwannomas of the brain: a 7-year experience; Sarma S et al.; OBJECTIVE: Nonvestibular schwannomas are uncommon tumors of the brain . Trigeminal nerve schwannomas are the most common of this group, followed by glossopharyngeal, vagal, facial, accessory, hypoglossal, oculomotor, trochlear, and abducens nerve schwannomas, in descending order of frequency . We present a series of nonvestibular schwannomas that were surgically treated during a 7-year period . METHODS: Forty-six patients with schwannomas of Cranial Nerves V (26 cases), VII (7 cases), IX, X, and XI (9 cases), XII (3 cases), and III (1 case) were microsurgically treated by the senior author (LNS) during a 7-year period, from 1993 to 2000 . The clinical presentations, operative approaches, complications, and results were studied . RESULTS: Forty-five patients underwent gross total tumor resection in the first operation . One patient who had undergone subtotal tumor resection in the initial operation experienced a large recurrence after 4 years, and gross total tumor resection was achieved in the second operation . There were no postoperative deaths . Postoperative morbidity consisted of cerebrospinal fluid leaks for 5 patients (3 patients required a second operation to repair the leak, and 2 patients responded to lumbar drain placement), meningitis for 3 patients (2 cases were aseptic and 1 involved bacterial meningitis, which resolved with antibiotic therapy), vasospasm requiring angioplasty for 1 patient, temporary hemiparesis for 2 patients (who experienced good recoveries), and permanent hemiparesis for 1 patient . New cranial nerve deficits were observed for 24% of patients but were usually partial . The mean follow-up period was 33.3 months (range, 0.2-93 mo) . No patient experienced tumor recurrence after complete tumor removal . The patient who experienced regrowth of the tumor did not exhibit recurrence after the second operation . The Karnofsky Performance Scale scores at the latest follow-up examination were 80 or more for 45 patients (98%) and 70 for 1 patient . CONCLUSION: Nonvestibular schwannomas can be treated via microsurgical excision, with excellent functional results . Recurrence is rare after total tumor excision, although much longer follow-up monitoring is required. Ophthalmologe, 2002 Jan, 99(1), 49 - 52 {Mono- or bilateral abducens paralysis as the initial symptom of sinus vein thrombosis}; Lang M et al.; BACKGROUND: Sinus vein thrombosis is a rare intracerebral complication of mastoiditis . We report on the clinical ophthalmologic symptomatology of this secondary illness . PATIENTS AND METHODS: History: two young female patients, aged 14 and 3.5 years, presented at our pediatric ophthalmology section due to diplopia . Both girls had suffered 1-2 weeks earlier from otitis media, which had been treated with antibiotics . Other neurological symptoms were not reported . CLINICAL COURSE: Best corrected visual acuity was 20/20 OD/OS in both patients . Ocular alignment revealed a bilateral abduction deficit in the 14-year-old girl and a monolateral abduction deficit of the right eye in the younger patient . Ophthalmoscopic examination evidenced bilateral papilledema in both patients . Magnetic resonance tomography and magnetic resonance angiography showed mastoiditis and thrombosis of the sigmoid and transverse sinuses . THERAPY: Following mastoidectomy, high-dose antibiotic therapy, and full-dose heparin therapy, rapid improvement occurred . CONCLUSIONS: Thrombosis of the sigmoid sinus following mastoiditis is a rare but severe complication of middle ear inflammation . Immediate surgical and antibiotic therapy is necessary . Symptoms can possibly occur even when the primary focus seems to resolve. J Surg Res, 2002 Feb, 102(2), 119 - 25 Chronic left heart catheterization for microvascular blood flow determination in the rabbit: a minimally invasive technique using specially designed port devices; Hoffmann JN et al.; BACKGROUND: This study describes a modified catheterization technique with subcutaneously implanted port catheters to be inserted in a retrograde manner across the aortic valve into the left heart ventricle through the right carotid artery to measure organ perfusion . MATERIALS AND METHODS: The specially designed arterial port catheters were implanted in New Zealand rabbits (n = 11, 3.7 +/- 0.1 kg {mean +/- SEM}) under iv anesthesia (medetomidine/ketamine) and single-shot perioperative antibiotic therapy . Hemodynamics were registered continuously during the operation via an ear artery catheter . RESULTS: Implantation of ports was performed in all animals (11/11) without major complications (mean operation time: 70 +/- 3 min) . We did not observe catheter-associated arrhythmia, fall in mean arterial pressure (MAP before and post OP: 70 +/- 2 and 68 +/- 2 Torr, respectively), or change in arterial oxygen saturation (SaO2 before and post OP: 89 +/- 3 and 95 +/- 2%, respectively) . With a specifically modified microsurgical insertion technique, cerebral blood supply was effectively preserved as evidenced from postmortem histological examinations, cerebral blood flow determination with fluorescent microspheres, and measurement of S-100b protein serum concentrations, a specific marker of neuronal damage . The positioning of the catheter tip in the left ventricle was found to be correct in 10/11 animals . CONCLUSIONS: Repeated and atraumatic microsphere injections into the left ventricle have become feasible by transcutaneous puncture of subcutaneous port systems over several weeks under light sedation . Hence, this new approach (i) avoids the necessity of repeated intracardiac injections and port insertions via thoracotomy, thus reducing the perioperative stress for the animals, and (ii) allows for the first time minimally invasive repetitive and chronic measurements of regional organ blood flow under various experimental settings . (c)2001 Elsevier Science. Intern Med, 2002 Jan, 41(1), 30 - 3 Recurrent pneumonia due to persistent Chlamydia pneumoniae infection; Miyashita N et al.; Two cases of recurrent pneumonia due to Chlamydia pneumoniae are described . C . pneumoniae was continuously detected from the nasopharynx in both patients by the polymerase chain reaction and/or culture even with appropriate antibiotic therapy during the first episode . After eradication of C . pneumoniae with long-term macrolide therapy, the respiratory symptoms of both patients completely disappeared and no relapse was observed . These data indicate that new treatment strategies may be necessary to eradicate the organism in patients prone to persistent infection. Mund Kiefer Gesichtschir, 2001 Nov, 5(6), 357 - 61 {Complications in surgical treatment of malocclusions . Report of 50 years experience}; Maurer P et al.; BACKGROUND: During the past few decades, orthognathic surgery has become routine in oral and maxillofacial surgery . As these surgical interventions are elective, the goal is a low complication rate . The aim of this study was to analyze the intraoperative and postoperative complications after orthognathic surgery without considering orthodontic relapse . PATIENTS AND METHODS: The medical files of 507 patients were reviewed who had been treated in the department of oral maxillofacial surgery at the Martin-Luther-Universitat in Halle-Wittenberg during a period of 51 years . The indication for orthognathic surgery was mandibular hyperplasia in 314 cases (61.9%), mandibular hypoplasia in 69 cases (13.6%), mandibular hyperplasia with a frontal open bite in 53 cases (10.5%), maxillary hyperplasia with a cleft in 30 cases (5.9%), maxillary hyperplasia in 22 cases (4.3%), severe laterognathia in 10 cases (2.1%), and isolated frontal open bite in 9 cases (1.5%) . The surgical procedures were as follows: bilateral sagittal split osteotomy (n = 336, 66%), Le Fort I osteotomy (n = 29, 5.9%), bimaxillary osteotomy (n = 35, 6.3%), and segment osteotomy (n = 107, 21.1%) . Rigid fixation was used in 147 patients . RESULTS: In 55% of the patients a postoperative neurosensory deficit of the inferior alveolar nerve was observed, which was only found in 28% after 1 year . Inflammatory wound healing was found in 5.3% of the patients . CONCLUSION: Due to antibiotic perioperative prophylaxis and modern rigid osteosynthesis devices, orthognathic surgery has become a routine method in maxillofacial surgery with predictable surgical results. Arch Intern Med, 2002 Jan 28, 162(2), 153 - 60 Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study); Treiber G et al.; BACKGROUND: Short-term therapies for eradicating Helicobacter pylori in selected patients might offer advantages in terms of costs, compliance, and adverse effects in contrast to standard 1-week triple therapy . METHODS: To determine eradication success and influencing factors in a new short-term quadruple therapy, a total of 243 patients positive for H pylori were randomly assigned to 1 of 3 regimens according to age, smoking status, and diagnosis: a 5-day treatment with 3 antibiotics (amoxicillin, 1 g twice daily {bid}; clarithromycin, 250 mg bid; and metronidazole, 400 mg bid) and lansoprazole (30 mg bid {L5; reference treatment}) or ranitidine hydrochloride (300 mg bid {R5}), or the same 3-day antibiotic-lansoprazole combination (L3) with a 2-day pretreatment with lansoprazole . RESULTS: A total of 234 patients completed the study . On an intention-to-treat basis, overall eradication of H pylori was confirmed in 86.4%: 89.2% in the L5 group vs 81.2% in the L3 group vs 88.8% in the R5 group; differences were not significant . Multiple logistic regression analysis showed that younger age (<55 years; P =.03), history of peptic ulcer disease (P =.04), smoking (P =.03), metronidazole resistance (P =.003), low ranitidine trough serum concentrations (P =.005), cytotoxin-associated gene A-negative strains in peptic ulcer disease (P =.04), and outer inflammatory protein A-positive strains (P =.02) were associated with eradication failure . CONCLUSIONS: This new quadruple H pylori eradication regimen is efficacious, safe, well tolerated, and cost saving, and may be a treatment option for patients older than 55 years with no history of peptic ulcer disease . Furthermore, strains that are sensitive to all antibiotics, cytotoxin-associated gene A-positive, and outer inflammatory protein A-negative could be suitable for short-term quadruple therapy . Patients with an unfavorable combination of characteristics should be treated for a minimum of 7 days. Int J Clin Pharmacol Ther, 2002 Jan, 40(1), 20 - 2 Hallucinations with therapeutic doses of clarithromycin; Jimenez-Pulido et al.; OBJECTIVE: Hallucinations caused by adverse reactions to medication are not uncommon and a wide variety of drugs may be involved . We present a case of hallucinations caused by therapeutic doses of oral clarithromycin (500 mg b.i.d) . CASE REPORT: A 32-year-old woman attended the Emergency Department of the hospital with severe visual hallucinations together with marked anxiety and nervousness following the second dose of clarithromycin, which was the only medication she was taking . The antibiotic was identified as the possible cause of the clinical manifestations and was stopped immediately . The patient did not require hospitalization and was discharged a few hours later with no signs of neurological disturbances . Clarithromycin was substituted by amoxycillin-clavulanic acid (500/125 mg) t.i.d . CONCLUSIONS: The temporal relationship between commencement of antibiotic therapy and the appearance of hallucinations, together with the fact that the symptoms disappeared once the antibiotic was suspended, support a causal relationship between clarithromycin and the hallucinations . Further support for a causal relationship was obtained by application of Naranjo's algorithm which gave a likelihood level for causality of PROBABLE. Chin J Traumatol, 2001 Nov, 4(4), 239 - 41 Glasgow Coma Scale, brain electric activity mapping and Glasgow Outcome Scale after hyperbaric oxygen treatment of severe brain injury; Ren H et al.; OBJECTIVE: To study the effect of hyperbaric oxy gen (HBO) treatment of severe brain injury . METHODS: Fifty-five patients were divided into a treatment group (n=35 receiving HBO therapy) and a control group (n=20 receiving dehydrating, cortical steroid and antibiotic therapy) to observe the alteration of clinic GCS (Glasgow Coma Scale), brain electric activity mapping (BEAM), prognosis and GOS (Glasgow Outcome Scale) before a nd after hyperbaric oxygen treatment . RESULTS: In the treatment group GCS, BEAM and GOS were improved obviously after 3 courses of treatment, GCS increased from 5.1 to 14.6 (P<0.01-0.001),the BEAM abnormal rate reduced from 94.3% to 38% (P<0.01-0.001), the GOS good-mild disability rate was 83.7%, and the middle-severe disability rate was 26.3% compared with the control group . There was a statistic significant difference between the two groups (P<0.01-0.001) . CONCLUSIONS: Hyperbaric oxygen treatment could improve obviously GCS, BEAM and GOS of severe brain injury patients, and effectively reduce the mortality and morbidity . It is an effective method to treat severe brain injury. Chin J Traumatol, 2001 Aug, 4(3), 187 - 9 Early treatment of wounds polluted by sea water; Li C et al.; During construction or training at sea, wounds are commonly seen and irresistibly polluted by sea water . An early and proper treatment of wounds polluted by sea water is very important for wound healing and function recovery of extremities . Some wounds even result in vegetation . In this study, we have reported the treatment results of 132 cases of wounds polluted by sea water admitted from 1985 to 1999. BMC Infect Dis . 2002;2(1):1 . Epub 2002 Jan 30. Prevalence and risk factors for vaginal Candida colonization in women with type 1 and type 2 diabetes; de Leon EM et al.; BACKGROUND: Diabetes mellitus increases the rate of vaginal colonization and infection with Candida species METHODS: We surveyed women with diabetes receiving care at either an urban or suburban diabetes clinic to examine the relationship between vaginal Candida colonization, diabetes type and duration, and HbA1c level . 101 participants completed the self-administered questionnaire and self-collected a vaginal swab for Candida culture . Candida colonization was similar by age and race . RESULTS: Type 1 diabetics were three times as likely as type 2 diabetics to be colonized with any Candida species (OR = 3.4; 95% CI: 1.03, 11.41; p = 0.04); even after adjusting for abnormal HbA1c, which had an independent effect (OR = 1.4; 95% CI: 1.04, 1.76; p = 0.02) . Recent antibiotic use (OR = 4.5; 95% CI: 1.18, 16.79; p = 0.03), lifetime history of chlamydia (OR = 5.8; 95% CI: 1.09, 30.54; p = 0.04), and performing oral sex during the past 2 weeks (OR = 4.9; 95% CI:0.84, 28.27; p = 0.08) were also associated with Candida carriage after adjusting for diabetic type and abnormal HbA1c . C . albicans was isolated from the majority of colonized type 1 participants (56%), while C . glabrata was the most common isolate among colonized type 2 participants (54%) . CONCLUSIONS: Improving glucose control and possibly modifying sexual behavior may reduce risk of Candida colonization, and potentially symptomatic infection, among women with diabetes. J Chromatogr A, 2002 Jan 18, 943(2), 227 - 34 High-performance liquid chromatography determination of Zn-bacitracin in animal feed by post-column derivatization and fluorescence detection; Capitan-Vallvey LF et al.; A sensitive and selective method is presented for the determination of Zn-Bacitracin in adulterated animal feed by reversed-phase ion-pair high-performance liquid chromatography and post-column derivatization with o-phthalaldehyde prior to fluorescence detection . The calibration function was estimated to be between 8.0 and 65.0 mg l(-1) of Zn-BC . The detection and quantification limits of the chromatographic method were 2.5 and 7.5 mg 1(-1), respectively . Using the extraction procedure of Zn-Bacitracin from the feedstuff that we recently proposed and applying this new chromatographic method, it was possible to detect this antibiotic at levels below 5 mg kg(-1) in different kinds of feedstuffs with a standard deviation less than 6.0%. Trends Plant Sci, 2002 Feb, 7(2), 84 - 91 Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology; Daniell H et al.; Chloroplast genomes defied the laws of Mendelian inheritance at the dawn of plant genetics, and continue to defy the mainstream approach to biotechnology, leading the field in an environmentally friendly direction . Recent success in engineering the chloroplast genome for resistance to herbicides, insects, disease and drought, and for production of biopharmaceuticals, has opened the door to a new era in biotechnology . The successful engineering of tomato chromoplasts for high-level transgene expression in fruits, coupled to hyper-expression of vaccine antigens, and the use of plant-derived antibiotic-free selectable markers, augur well for oral delivery of edible vaccines and biopharmaceuticals that are currently beyond the reach of those who need them most. Cancer Metastasis Rev, 2001, 20(1-2), 69 - 78 Resistance to rapamycin: a novel anticancer drug; Huang S et al.; The macrocyclic lactone rapamycin has an established place as an immune suppressive agent in organ transplantation . However, more recently it has been recognized as an inhibitor of pathways that may be activated during malignant transformation and tumor progression . Thus, increasing interest is being directed to this class of antibiotic as potential antitumor agents . Here we summarize the history, mechanism of action, and mechanisms of resistance to rapamycin. Med Klin (Munich), 2002 Jan 15, 97(1), 34 - 9 {Manifestation of hyper-IgE syndrome in advanced HIV-1 infection}; Lange CG et al.; BACKGROUND: The classical triad of Job's syndrome (Hyper-IgE syndrome), a congenital immunodeficiency disorder, includes recurrent "cold" abscesses, pneumonias and extreme elevations of the serum IgE concentration . CASE REPORT: A 49-year-old HIV-1 infected patient with a viral load of 268,852 copies/ml plasma and a CD4+ T lymphocyte concentration of 2 cells/microliter blood was admitted to our clinic for antibiotic therapy and incision and drainage of several large abscesses . The patient suffered for approximately 5 years from recurrent pneumonias, abscesses and multiple allergies . The serum IgE level was over 100-fold elevated and, after analysis of archived serum samples, had not been influenced by fluctuations in the plasma viral load or changes in the CD4+ T lymphocyte concentration in previous years . No stigmata of Job's syndrome were present prior to the patient's HIV-1 infection . Observations on other patients with AIDS and recurrent abscesses suggest that in these patients hyperimmunoglobulinemia E is related to a cytokine class switch from a TH1 to a TH2 profile as CD4+ T lymphocytes are depleted . CONCLUSIONS: Following CD4+ T lymphocyte depletion, it has been rarely documented that HIV-1 infected patients may develop clinical symptoms and a hyperimmunoglobulinemia E, similar to patients with the congenital immunodeficency of Job's syndrome. Blood, 2002 Feb 15, 99(4), 1165 - 73 Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti-Epstein-Barr virus potential through both culture-dependent and selection process-dependent mechanisms; Sauce D et al.; To modulate alloreactivity after hematopoietic stem cell transplantation, suicide gene-expressing donor T cells can be administered with an allogeneic T-cell-depleted bone marrow graft . Immune competence of such cells is a critical issue . The impact of the ex vivo gene transfer protocol (12-day culture period including CD3/interleukin-2 {IL-2} activation, retroviral-mediated gene transfer, and G418-based selection) on the anti-Epstein-Barr virus (EBV) potential of gene-modified cells has been examined . Cytotoxic (pCTL) and helper (pTh) cell precursor limiting dilution assays, interferon-gamma enzyme-linked immunospot, or fluorescence-activated cell sorter analysis after tetrameric HLA-A2/EBV peptide complexes revealed that the frequency of anti-EBV T cells was lower in gene-modified cells (GMCs) than in similarly cultured but untransduced T cells and was even lower than in fresh peripheral blood mononuclear cells, demonstrating both an effect of the culture and of the transduction or selection . The culture-dependent loss of EBV-reactive cells resulted from the preferential induction of activation-induced cell death in tetramer(+) cells . Replacing the initial CD3/IL-2 activation by CD3/CD28/IL-2 partially restored the anti-EBV response of GMCs by reducing the initial activation-induced cell death and enhancing the proliferation of EBV-tetramer(+) cells . Moreover, the G418 selection, and not the transduction, was directly toxic to transduced tetramer(+) cells . Replacing the G418 selection by an immunomagnetic selection significantly prevented the selection-dependent loss of EBV-specific cells . Overall, ex vivo gene modification of primary T cells can result in a significant reduction in EBV-reactive T cells through both culture-dependent and selection-dependent mechanisms . Improving immune functions of GMCs through modifications of the cell culture conditions and transduction/selection processes is critical for further clinical studies. Ann Rheum Dis, 2002 Mar, 61(3), 251 - 3 Efficacy of isoniazid prophylaxis in patients with systemic lupus erythematosus receiving long term steroid treatment; Gaitonde S et al.; OBJECTIVE: To study the efficacy of isoniazid prophylaxis (INHP) in patients with systemic lupus erythematosus (SLE) receiving long term glucocorticosteroid treatment . PATIENTS AND METHODS: Treatment with INHP (5 mg/kg/day, max 300 mg/day) together with pyridoxine 10 mg/day for one year was started in all patients with SLE seen between January 1994 and December 1999 and followed up thereafter . Clinical examination and chest radiography were carried out in all patients before the start of INHP treatment . A liver profile was obtained only if liver toxicity was suspected owing to nausea, loss of appetite, and icterus . Only the data of those patients who completed the INHP treatment or who were withdrawn owing to toxicity have been analysed . This was compared with the results of an earlier study of the incidence of tuberculosis (TB) in patients with SLE not receiving INHP . RESULTS: Ninety seven patients were included, of whom 95 completed one year's treatment with INHP . Treatment was discontinued in two owing to toxicity: hepatitis in one and peripheral neuropathy in one, at eight and 10 months, respectively . One patient developed TB within one month of starting INHP . Seventy patients were followed up further for at least one year (mean 26.4 months, range 12-60 months) after completion of the INHP treatment . During this period one patient developed TB after one month . No deaths due to TB or hepatitis occurred . In comparison with earlier series the incidence of TB decreased from 11% to 2%, a reduction of 82% . The cost of treatment for each case of TB prevented in the first year was 5800 rupees . CONCLUSION: INHP is safe and effective in SLE. Hosp Med, 2002 Jan, 63(1), 28 - 32 Advances in the management of CSF rhinorrhoea; Swift AC et al.; Cerebrospinal fluid fistulae are under-diagnosed, difficult to locate and often clinically silent . They are potentially lethal and carry a long-term cumulative risk of meningitis . They should be fully investigated and treated aggressively . Current endoscopic techniques combined with intrathecal fluorescein dye enable most defects to be located and sealed with minimal morbidity. Yakugaku Zasshi, 2002 Jan, 122(1), 1 - 27 {Development of new reactions and their pharmaceutical application based on the molecular structure characteristics}; Nagao Y; The author and his group have been developing new reactions based on molecular structure characteristics; sigma-symmetric bifunctional molecules, dipole-dipole repulsion, active amide structures, latent active species, orbital-orbital interactions, nonbonded interactions, strained structures, allenic structures, etc . Various new reactions such as asymmetric aminolyses and Dieckmann-type cyclizations of prochiral sigma-symmetric dicarboxylic diamides, asymmetric aldol-type reactions onto gamma-hydroxybutenolides and asymmetric imine alkylations onto omega-acetoxy lactams using chiral Sn(II) enolates, asymmetric Pummerer-type reactions, cascade reactions and endo-mode cyclizations exploiting alpha,beta-unsaturated allenic esters and ketones, base- and palladium-promoted ring-expansion reactions, and syntheses of alpha-substituted serines and 1-azabicyclo {1.1.0} butane have been achieved . These new reactions were applied to the synthetic development of new seed and lead compounds (SH-enzyme inhibitors, tumor inhibitors, and antibiotics) with the aim of synthesizing new drugs . Asymmetric syntheses of (+)-Prelog-Djerassi lactonic acid methyl ester, (+)-carbacyclin, ISP-I (myriocin), (+)-conagenin, Geissman-Waiss lactone, biapenem (a new carbapenem antibiotic), thienamycin-like gamma-lactam, and bicyclic alkaloids were also achieved by utilizing these reactions . Evaluation and molecular design of the seed and model compounds for angiotensin II receptor antagonists, tumor inhibitors, and antibiotics have been investigated on the basis of QRSA and/or nonbonded S...X (X=O, N, S, halogens) interaction concepts. Nihon Kokyuki Gakkai Zasshi, 2001 Oct, 39(10), 787 - 91 {An autopsy case of idiopathic interstitial pneumonia with diffuse alveolar hemorrhage due to acute exacerbation}; Kuwano K et al.; There has hitherto been no report describing idiopathic interstitial pneumonia associated with diffuse alveolar hemorrhage, but we herein report one such rare case . A 75-year-old man who had received a diagnosis of idiopathic interstitial pneumonia had been followed in our hospital since 1995, and had been treated with cyclophosphamide since September 1999 . He discontinued taking cyclophosphamide without informing us, and two months later he was admitted to our hospital with deterioration of dyspnea on September 13, 2000 . Since chest radiography and CT findings demonstrated alveolar infiltrates in the right middle lung field, he was treated with antibiotic agents . Although no deterioration of symptoms occurred, on September 14 he began to suffer rapidly progressive dyspnea accompanied with production of bloody sputum, which eventually developed into full-blown hemoptysis in the evening of September 15 . He died of respiratory failure early the next morning . The autopsy findings demonstrated diffuse alveolar hemorrhage, diffuse alveolar damage, interstitial pneumonia, and pulmonary fibrosis. J Thorac Imaging, 2002 Jan, 17(1), 84 - 8 Intracavitary hematoma simulating mycetoma formation; Knower MT et al.; SUMMARY: This case report details the initial radiographic findings of a patient with mixed connective-tissue disease who presented with significant hemoptysis . Several radiographic findings suggested mycetoma formation, prompting appropriate antibiotic therapy; however, the rapid resolution and subsequent reappearance of the lesion on serial images pointed toward a diagnosis of hemorrhage into a preexisting cavity . Chest radiographic and computed tomographic findings commonly described as pathognomonic for the diagnosis of mycetoma are, in fact, nonspecific and can be simulated by several other entities that result in intracavitary masses . Familiarity with these radiographic "mimickers" of mycetoma will aid in avoiding misdiagnosis and unnecessary or improper invasive interventions when the appropriate clinical history and course of disease are appreciated. Curr Opin Chem Biol, 2002 Feb, 6(1), 63 - 9 Rainbow's end: the quest for multiplexed fluorescence quantitative analysis in proteomics; Patton WF et al.; During the past two years, the performance of fluorescence-based protein detection methods has demonstrably eclipsed conventional technologies such as colloidal Coomassie Blue and silver staining with respect to detection sensitivity, quantitative accuracy and compatibility with modern protein identification and characterization procedures . At this point, fluorescence-based methods are poised to offer unprecedented new capabilities in proteomics investigations through the performance of multi-parameter quantitative measurements . The feasibility of such measurements has already been demonstrated through the specific detection of antibiotic-binding proteins, drug-metabolizing enzymes or post-translationally glycosylated proteins, along with the total protein expression profile from electrophoretically separated, complex biological specimens. An Esp Pediatr, 2002 Feb, 56(2), 185 - 8 {Pyriform sinus fistulae}; Martin Del Rey R et al.; Pyriform sinus fistulae (PSF) are rare branchial pouch anomalies . In most previously described cases the anomaly is located on the left side . PSF should be suspected in cervical inflammatory processes (cervical abscesses and types of suppurative thyroiditis) . We report two cases of acute thyroiditis and deep cervical abscesses secondary to PSF, which were diagnosed and treated in our hospital in the last 2 years . Both presented inflammatory cervical masses associated with painful swallowing, high fever and laboratory findings compatible with acute infection.In both cases the diagnosis of PSF was confirmed by barium esophagogram . Cervical ultrasonography and computed tomography were also performed . The treatment of choice consists of broad-spectrum antibiotic therapy during acute exacerbation and subsequent fistulectomy . Definitive surgical treatment prevents recurrences. Biochemistry, 2002 Feb 12, 41(6), 1965 - 71 Specific binding of Ro 09-0198 (cinnamycin) to phosphatidylethanolamine: a thermodynamic analysis; Machaidze G et al.; Ro 09-0198 (cinnamycin) is a tetracyclic peptide antibiotic that is used to monitor the transbilayer movement of phosphatidylethanolamine (PE) in biological membranes during cell division and apoptosis . The molecule is one of the very rare examples where a small peptide binds specifically to a particular lipid . In model membranes and biological membranes containing phosphatidylethanolamine, Ro 09-0198 forms a 1:1 complex with this lipid . We have measured the thermodynamic parameters of complex formation with high sensitivity isothermal titration calorimetry and have investigated the structural consequences with deuterium and phosphorus solid-state NMR . Complex formation is characterized by a large binding constant, K0, of 10(7) to 10(8) M(-1), depending on the experimental conditions . The reaction enthalpy, DeltaHdegrees, varies between zero at 10 degrees C to strongly exothermic -10 kcal/mol at 50 degrees C . For large vesicles with a diameter of approximately 100 nm, DeltaHdegrees decreases linearly with temperature and the molar heat capacity of complex formation can be evaluated as = -245 cal/mol, indicating a hydrophobic binding mechanism . The free energy of binding is DeltaGdegrees = -10.5 kcal/mol and shows only little temperature dependence . The constancy of DeltaGdegrees together with the distinct temperature-dependence of DeltaHdegrees provide evidence for an entropy-enthalpy compensation mechanism: at 10 degrees C, complex formation is completely entropy-driven, at 50 degrees C it is enthalpy-driven . Varying the PE fatty acid chain-length between 6 and 18 carbon atoms produces similar binding constants and DeltaHdegrees values . Addition of Ro 09-0198 to PE containing bilayers eliminates the typical bilayer structure and produces 2H- and 31P-NMR spectra characteristic of slow isotropic tumbling . This reorganization of the lipid matrix is not limited to PE but also includes other lipids. Eye, 2001 Dec, 15(Pt 6), 774 - 80 Orbital involvement in sickle cell disease: a report of five cases and review literature; Ganesh A et al.; PURPOSE: To present five cases of orbital infarction in sickle cell disease and review relevant literature . METHOD: We reviewed the hospital records of 5 patients with sickle cell disease who developed a periorbital swelling during a vaso-occlusive crisis and were managed at our hospital between April 1992 and June 2000 . RESULTS: The 5 patients (4 with homozygous sickle cell disease and 1 with sickle cell-beta-thalassaemia disease) were aged 6-15 years with a history of multiple admissions for vaso-occlusive crises . The periorbital swelling spread to the orbit in 4 cases and resulted in proptosis (2 cases), restriction of ocular motility and visual impairment . In all 4 cases, computed tomography and/or magnetic resonance imaging of the orbits showed a mass adjacent to the orbital wall . In 2 cases the mass was identified as a haematoma . Orbital wall infarction was demonstrated in 3 cases by bone/bone marrow scintigraphy . Epidural haematomas were detected by computed tomography in one case . All patients received intravenous fluids, analgesics, broad spectrum antibiotics and steroids, as well as simple or exchange transfusion, and responded well to medical management . CONCLUSIONS: Infarction of orbital bones during vaso-occlusive crises in sickle cell disease presents acutely with a rapidly progressive periorbital swelling . Haematomas frequently complicate the condition and, along with the inflammatory swelling, may lead to orbital compression syndrome . The condition is therefore sight-threatening, and necessitates prompt diagnosis and appropriate management for resolution without adverse sequelae . Imaging techniques are invaluable in the evaluation of patients . The majority of cases resolve with conservative treatment that includes steps to combat the vaso-occlusive crisis and use of systemic steroids under antibiotic cover. Eur J Cardiothorac Surg, 2002 Feb, 21(2), 314 - 8 Surgery for Mycobacterium avium complex lung disease in the clarithromycin era; Shiraishi Y et al.; OBJECTIVE: Since the introduction of clarithromycin, it has been assumed that pulmonary Mycobacterium avium complex (MAC) disease can be treated with medication alone . This study examines whether surgery can still play an important role in the management of MAC lung disease in the current era . METHODS: Between April 1993 and January 2001, 21 patients (11 men and 10 women) underwent a pulmonary resection for MAC infection . The median age of the patients was 56 years (range: 27-67 years) . None of the patients were immunocompromised . Regimens employing clarithromycin were initiated preoperatively in all patients . The indications for surgery were failure of drug therapy in 19 patients and discontinuation of chemotherapy because of drug toxicity in two patients . The pulmonary resections (19 right lung, 2 left lung) performed included lobectomy in 16 patients, pneumonectomy in three, bilobectomy in one, and lobectomy plus segmentectomy in one . RESULTS: All of the patients survived the surgery . Six major postoperative complications occurred in six patients (28.6%) and these included two bronchopleural fistulas after right pneumonectomy, two space problems, one prolonged air leak, and one case of interstitial pneumonia . All postoperative complications were manageable, and four of these were treated surgically . All patients had sputum-negative status after their operation . Relapse occurred in two patients (9.5%) at six months and two years postoperative, respectively . The first patient, who originally had a right upper lobectomy, underwent a left upper lobectomy during the follow-up period, attaining sputum conversion . The second patient underwent a right pneumonectomy and then died of respiratory failure four years postoperatively . This one late death was the only fatality . CONCLUSIONS: Although it is associated with relatively high morbidity, surgery provides a high sputum conversion rate for patients whose MAC disease responds poorly to drug therapy . Even in the present clarithromycin era, pulmonary resection remains the treatment of choice when MAC lung disease has not been successfully eradicated by drug treatment alone. Prescrire Int, 2001 Dec, 10(56), 175 - 7 Zanamivir: a second look . Still no tangible impact on influenza; Acanthamoeba keratitis after photorefractive keratectomy; Cornea and External Disease Division, Department of Ophthalmology, Boston University Medical Center, Boston, Massachusetts, USA . Rogerkaldawy@bmc.org A 37-year-old women developed severe suppurative keratitis immediately after having photorefractive keratectomy in her left eye . The keratitis was unresponsive to intensive topical antibiotic agents and topical and systemic steroids . Although the differential diagnosis included nonmicrobial and fungal keratitis, the clinical course and confocal microscopy suggested, and subsequent histopathologic examination confirmed, a diagnosis of Acanthamoeba keratitis . The amebic contamination probably resulted from exposure of the deepithelialized cornea to contaminated freshwater in a northern Wisconsin marsh . This case emphasizes the importance of encouraging patients with epithelial defects and bandage soft contact lenses to avoid exposure to contaminated freshwater until reepithelialization is complete. Am Fam Physician, 2002 Jan 15, 65(2), 265 - 70 The newborn examination: part II . Emergencies and common abnormalities involving the abdomen, pelvis, extremities, genitalia, and spine; Fuloria M et al.; Careful examination of the neonate at delivery can detect anomalies, birth injuries, and disorders that may compromise successful adaptation to extrauterine life . A newborn with one anatomic malformation should be evaluated for associated anomalies . If a newborn is found to have an abdominal wall defect, management includes the application of a warm, moist, and sterile dressing over the defect, decompression of the gastrointestinal tract, aggressive fluid resuscitation, antibiotic therapy, and prompt surgical consultation . Hydroceles are managed conservatively, but inguinal hernias require surgical repair . A newborn with developmental hip dysplasia should be evaluated by an orthopedist, and treatment may require use of a Pavlik harness . The presence of ambiguous genitalia is a medical emergency, and pituitary and adrenal integrity must be established . Early diagnosis of spinal lesions is imperative because surgical correction can prevent irreversible neurologic damage. Presse Med, 2001 Dec 22-29, 30(39-40 Pt 2), 70 - 9 {Pharmacology of non-steroidal anti-inflammatory drugs and ENT pathology}; Devillier P; 1 . BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) belong to a variety of chemical classes with no common features except the absence of a steroid structure . Their primary effect is pain relief, but also with anti-pyretic and anti-inflammatory effects . Basically prescribed for symptomatic relief, they do not have a curative effect on chronic disease processes . 2 . INFLAMMATORY EFFECTS OF PROSTANOIDS (THROMBOXANE A2 AND PROSTAGLANDINS): Inflammation basically results from the pro-algogenic and vascular effects of prostanoids . Their pro-algogenic effects are explained by sensitization of nociceptive nerve endings to the stimulating effect (algogenic) of kinins (bradykinin), serotonin and histamine . In addition, production of prostanoids in the brain has a thermoregulatory effect . 3 . MODE OF ACTION: NSAID have a common effect, inhibiting the production of prostanoids via reduced activity of two cyclo-oxygenases (COX-1 and COX-2) . COX-2 is an isoform predominantly expressed during the inflammatory process . Excepting two compounds recently marketed (celecoxib, rofecoxib) selective for COX-2, all other NSAID have few or no selective properties . COX-1 is implicated in the regulation of many physiological functions . Inhibition of COX-1 explains most of the classical side effects of non-selective NSAID . 4 . COMPARISON: It is classical to emphasize the interindividual variable anti-inflammatory and antalgesic effects of the different NSAID without developing a coherent explanation . In addition, it is very difficult to make objective comparisons between different NSAID because of the different sizes of the study populations, indications and dosages . There is no evidence favoring a given NSAID on the basis of its anti-inflammatory or antalgesic effect in a given indication; no hierarchy in terms of efficacy can be established . For acute pain, it is preferable to use oral NSAID absorbed rapidly to achieve rapid relief . 5 . PARACETAMOL: This antalgesic, antipyretic drug has no anti-inflammatory action . Its mechanism of action remains to be fully elucidated . It is not a member of the NSAID class and is a poor inhibitor of COX, particularly COX-2 (30% maximal inhibition) . For identical dose (1-3 g/d), the antalgesic activity of paracetamol is comparable to that of aspirin for pain in general . There does not appear to be any difference in the anti-pyretic efficacy between NSAID and paracetamol . 6 . OFFICIAL INDICATIONS: In general, NSAID are not indicated for anti-inflammatory action in the ENT conditions discussed here . It this light, the official indications in France published on November 14, 1988 concerning ENT disease in children and adults without risk factors is most noteworthy . It is stipulated that there is no need to institute NSAID treatment at an anti-inflammatory dose in combination with general antibiotic therapy, except when there is an important inflammatory component . This guideline does not concern NSAID at antalgesic and antipyretic doses used for ENT conditions with or without an infectious component . 7 . SELECTIVE INHIBITORS OF COX-2: Selective inhibitors are only indicated in two chronic inflammatory diseases: osteoarthritis and rheumatoid arthritis . There is no indication for these inhibitors in ENT disease . The only beneficial effect that has been demonstrated to date for the use of selective inhibitors of COX-2 is better digestive tract tolerance . 8 . ROLE OF PROSTANOIDS IN THE CLINICAL EXPRESSION OF ALLERGIC RHINITIS: It is insufficient to warrant use of NSAID in this disease, particularly due to the efficacy of anti-H1 and local corticosteroids . NSAID are not indicated in nasal polyposis and are even contraindicated in case of intolerance to NSAID, observed in about 15-20% of all patients with nasal polyposis . However, local application of lysine acetylsalicylate at progressive doses from 20 micrograms to 4 mg can reduce relapse by half after polypectomy . There is no proof of the efficacy of NSAID in chronic sinusitis and their efficacy has not been studied in laryngitis . Finally, there is no sufficient evidence, either from experimental data or clinical trials, to recommend NSAID for otitis, with the exception for an antalgesic and/or antipyretic effect . 9 . CHOOSING AN ANTI-INFLAMMATORY OR ANTALGESIC NSAID: The choice is generally guided by the frequency and severity of undesirable effects . These undesirable effects often appear during the first weeks of treatment . 10 . DIFFERENT ADVERSE EFFECTS: Digestive tract effects appear in 20 to 40% of the patients after a few weeks of treatment using anti-inflammatory doses . Symptomatic gastroduodenal ulcers, digestive bleeding, and perforations are the most serious adverse effects of NSAID . Nevertheless, the risk of such complications, compared with the number of prescriptions, is very low . At high dose (anti-inflammatory dose), age over 60 years and history of severe gastrointestinal complications are factors increasing the risk of severe gastrointestinal adverse effects of NSAID . Minor adverse effects, and more importantly severe adverse effects, are significantly reduced with selective COX-2 inhibitors compared with classical NSAID . It is important to note that these beneficial effects in terms of tolerance are not better than with NSAID treatments except for treatments at anti-inflammatory doses for more than one week . Selective COX-2 inhibitors would have the same adverse effect on the kidney as classical NSAID, as pointed out by the precautions for use published by the manufacturers . COX-2 is not expressed by platelets . Specific inhibitors do not inhibit platelet aggregation and do not lengthen bleeding time . Specific inhibitors, like classical NSAID, are not recommended for women desiring pregnancy, especially because the risk of a teratogenic effect has not been excluded . Conversely, for patients with asthma triggered by classical NSAID, selective COX-2 inhibitors do not trigger acute asthma . Finally, selective COX-2 inhibitors are not currently indicated for children and not for ENT disease. Plast Reconstr Surg, 2002 Feb, 109(2), 592 - 600 Free tissue coverage of chronic traumatic wounds of the lower leg; Gonzalez MH et al.; Thirty-eight consecutive patients who underwent 42 free flaps for chronic wounds of the lower leg were identified over an 11-year period . All wounds were open for a minimum of 1 month (mean, 40 months; median, 8 months; range, 1 month to 30 years) . The average age was 37 years (range, 7 to 68 years), there were 31 male patients and seven female patients, and the average follow-up time was 30 months (range, 12 to 72 months) . The original injury was an open fracture in 28 patients, wound dehiscence after open reduction and internal fixation of a closed fracture in nine patients, and a shrapnel wound in one patient . A total of 23 patients had osteomyelitis, which was classified as local (involving less than 50 percent of the bone diameter) in 15 patients and as diffuse (involving greater than 50 percent of the bone diameter or infected nonunion) in eight patients . The wounds were treated with sequential debridement, antibiotics, and flap coverage . Ancillary procedures included antibiotic beads in 18 patients, saucerization in 16, Ilizarov bone transport in three, calcanectomy in two, and fibular resection and ankle fusion in one . Thirty-four of 42 flaps survived, four having undergone a repeat free flap . There were three failures out of 25 flaps (12 percent) among those with a normal angiogram and five failures out of 15 flaps (33 percent) among those with an abnormal angiogram (p > 0.05) . The failure rate of those with osteomyelitis was six of 26 (23 percent) versus two of 26 (13 percent) for those without osteomyelitis (p > 0.05) . Successful reconstruction (bone healed, patient ambulatory and infection-free) was achieved in 33 of 38 patients (87 percent) . The failure of reconstruction for those patients with osteomyelitis was four of 23 (22 percent) versus one of 15 (7 percent) for others (p > 0.05) . The failure rate of flaps in patients with diffuse osteomyelitis was three of eight (38 percent) versus two of 30 for others (7 percent, p = 0.053) . The presence of diffuse osteomyelitis was associated with a lower rate of successful limb reconstruction . An abnormal angiogram and the presence of osteomyelitis both were associated with a lower rate of successful limb reconstruction, but this was not significant, probably because of the small size of the cohort. Equine Vet J, 2002 Jan, 34(1), 71 - 5 Caprine serum fraction immunomodulator as supplemental treatment of lower respiratory disease in the horse; Hamm D et al.; Suppurative lower airway disease is a common debilitating disease in performance horses and, while rarely fatal, is often recalcitrant to conventional therapy . A variety of treatments have been used to combat this condition and we conducted two types of studies to determine if caprine serum fraction--immunomodulator (CSFI), a nonspecific immunomodulator, improved recovery from lower respiratory disease . Two dose response studies were performed to ascertain the efficacy of CSFI . Horses were maintained daily on conventional antibiotic therapy . Respiratory tract exudate, nasal discharge, dyspnoea, chest auscultation and cough frequency were monitored weekly . One hundred percent of the horses treated with 2 i.m . injections of either 60 or 120 mg CSFI one week apart showed significant improvement with each weekly evaluation and were fully recovered by week 3 . Horses treated with 15 or 30 mg CSFI did not differ significantly from the control group . Only 10% of the control horses responded to conventional antibiotic therapy . An expanded field trial utilising 80 horses diagnosed with lower respiratory disease and housed at 4 equine clinics was conducted . Thirty-five percent of the 40 control horses, treated solely by conventional antibiotic therapies, recovered while 75% of the horses treated with a supplemental administration of 60 mg CSFI as described above recovered . The combined data from these studies showed that CSFI was able to promote an overall recovery from lower respiratory disease of 86%. Clin Perinatol, 2001 Dec, 28(4), 797 - 805 Antenatal corticosteroids in women with preterm premature rupture of the membranes; Vidaeff AC et al.; The authors believe that the literature provides sufficient evidence that antenatal corticosteroid administration is beneficial and safe even in conditions of ruptured membranes . The evidence by now is remarkably robust and one can be reasonably confident regarding the benefits of antenatal corticosteroids in the setting of ruptured membranes . As recently stated by a group of investigators from New Zealand, including Liggins, the originator of this historical medical intervention (antepartum corticosteroids), the safety and efficacy of corticosteroids in conditions of ruptured membranes is beyond any doubt . It is time to accept this reality and to move on to other unresolved issues, like the optimal dose and corticosteroid preparation, the optimal timing of treatment, or the optimal exposure interval. Clin Perinatol, 2001 Dec, 28(4), 787 - 96, vi Tocolytic therapy with preterm premature rupture of membranes; Fontenot T et al.; Tocolytic therapy with preterm premature rupture of membranes continues to be a controversial issue . Articles focusing on potential benefits and adverse outcomes associated with tocolysis in this disease process are reviewed . Although there may be some short-term neonatal benefit, further investigation of this issue is warranted. Gan To Kagaku Ryoho, 2002 Jan, 29(1), 115 - 8 {A case of locally recurrent breast cancer in which phlebothrombosis of the right leg after hormonal therapy using a high dose of toremifene citrate}; Sakuta M et al.; A 72-year-old female had undergone mastectomy at the age of 67 for right breast cancer (T2a, n1 alpha, positive for ER) . In the surgery the pectoralis muscle was preserved . For adjuvant therapy, 20 mg/day of tamoxifen was orally administered for 5 years . Six years after surgery, relapse was detected in the right major pectoralis muscle . Irradiation at this site and oral administration of 120 mg/day of toremifene citrate were started . The patient had a medical history of diabetes, and the control of her blood sugar was poor . About 2 months after oral administration of toremifene citrate was started, flares with blebs and swelling were observed in the right lower leg, suggesting acute phlebothrombosis of the right lower limb . The symptoms were ameliorated by intravenous administration of heparin and an antibiotic . In administering a high dose of toremifene citrate to patients with complications, careful follow-up is needed. Magy Seb, 2001 Dec, 54 Suppl, 31 - 4 {The state of heart transplantation in Hungary}; Bodor E et al.; The first heart transplantation was performed in 1992 in Hungary . In the last nearly ten years 42 patients have got new heart . Among them 16 died . Authors discuss the changes of the surgical techniques and the postoperative treatment during this period, and what results were obtained with these new methods . They deal with problems, why so small number of the transplantations were performed . The causes of the death of the 16 patients were discussed. Bioorg Med Chem Lett, 2002 Feb 11, 12(3), 283 - 6 Isolation of 3' -O-acetylchloramphenicol: a possible intermediate in chloramphenicol biosynthesis; Gross F et al.; 3' -O-acetylchloramphenicol, commonly formed from chloramphenicol by resistant bacteria, has been isolated from the antibiotic-producing organism . Biosynthetic experiments suggest that it is a protected intermediate in chloramphenicol biosynthesis, implicating acetylation as a self-resistance mechanism in the producing organism. J Mol Biol, 2002 Jan 25, 315(4), 513 - 27 Mistranslation induced by streptomycin provokes a RecABC/RuvABC-dependent mutator phenotype in Escherichia coli cells; Balashov S et al.; Translational stress-induced mutagenesis (TSM) refers to the mutator phenotype observed in Escherichia coli cells expressing a mutant allele (mutA or mutC) of the glycine tRNA gene glyV (or glyW) . Because of an anticodon mutation, expression of the mutA allele results in low levels of Asp-->Gly mistranslation . The mutA phenotype does not require lexA-regulated SOS mutagenesis functions, and appears to be suppressed in cells defective for RecABC-dependent homologous recombination functions . To test the hypothesis that the TSM response is mediated by non-specific mistranslation rather than specific Asp-->Gly misreading, we asked if streptomycin (Str), an aminoglycoside antibiotic known to promote mistranslation, can provoke a mutator phenotype . We report that Str induces a strong mutator phenotype in cells bearing certain alleles of rpsL, the gene encoding S12, an essential component of the ribosomal 30 S subunit . The phenotype is strikingly similar to that observed in mutA cells in its mutational specificity, as well as in its requirement for RecABC-mediated homologous recombination functions . Expression of Str-inducible mutator phenotype correlates with mistranslation efficiency in response to Str . Thus, mistranslation in general is able to induce the TSM response . The Str-inducible mutator phenotype described here defines a new functional class of rpsL alleles, and raises interesting questions on the mechanism of action of Str, and on bacterial response to antibiotic stress . Cryobiology, 2001 Aug, 43(1), 81 - 4 Characterization of ultrastructural damage of valves cryopreserved under standard conditions; Villalba R et al.; Cryopreserved allograft valves are increasingly being used as valvular replacements . This study was conducted to characterize the ultrastructural damage on the allograft valves obtained by a current standard protocol of valve procurement, antibiotic exposure, and cryopreservation, as a basis for future studies on allograft valve preservation . Materials used were seven aortic and seven pulmonary fresh porcine valves, which were cryopreserved according to the requirements of the American and European Associations of Tissue Banks . The samples were randomly assigned into four groups: (1) fresh, untreated; (2) fresh, treated with antibiotics for 24 h.; (3) treated with antibiotics and exposed to dimethyl sulfoxide (without freezing); and (4) treated with antibiotics, exposed to dimethyl sulfoxide, and then cryopreserved and stored until the study . All tissue samples were processed simultaneously for routine light microscopy and transmission electron microscopy . Fresh-untreated, antibiotic-treated, and dimethyl sulfoxide-exposed valves showed adequate preservation of cellular components . However, after cryopreservation significant damage was observed in fibroblasts with signs of apoptotic cellular injury . Our observation suggests that apoptosis occurs during valve processing . This apoptotic process may be related to various factors, including chemical injury or hypoxia . Br Poult Sci, 2001 Dec, 42(5), 564 - 8 Influence of zinc bacitracin, light regimen and dustbathing on the health and welfare of broiler chickens; Stub C et al.; 1 . The influence of zinc bacitracin, an antibiotic growth promoter, and the combined influence of two environmental factors (8 h of darkness and access to sand) on health and welfare variables were studied in 96 broiler chickens (kept as pairs) . 2 . Chickens fed with zinc bacitracin (ZB) had a higher frequency of tibial dyschondroplasia (TD) and a higher frequency of dustbathing than chickens fed without zinc bacitracin . 3 . When 42 d old, chickens exposed to 8 h of darkness and access to sand were heavier than chickens reared under continuous light and with no access to sand . 4 . Fluctuating asymmetry was higher in the 'light/no sand' groups than in the 'night/sand + ZB' group . 5 . There was a negative correlation between tonic immobility and weight and a positive correlation between weight and TD. J Periodontol, 2001 Dec, 72(12), 1755 - 9 Myospherulosis complicating cortical block grafting: a case report; Fisher SC et al.; BACKGROUND: Myospherulosis of the oral cavity is an inflammatory, granulomatous lesion historically associated with the use of petrolatum-based antibiotic ointment placed in third molar extraction sites to prevent postoperative infection . METHODS: A case of bilateral myospherulosis is presented, in which large lesions complicated the procurement of a cortical block graft used to prepare a mandibular molar edentulous space for implant placement . By obtaining the block graft from a more lateral location on the mandible, an adequate graft was procured and was successfully grafted into an atrophic edentulous ridge . RESULTS: The cortical block graft was successfully incorporated by the recipient site, which received a wide-body, threaded dental implant 6 months later . Healing was uncomplicated, and a functional implant-supported restoration was successfully achieved . CONCLUSIONS: Myospherulosis, though rare today, may present a significant obstacle to the procurement of cortical block grafts . In this case, thorough debridement of the material resulted in subsequent healing of the myospherulosis defect, but prevented procurement of the cortical graft from the planned site . The dimension and volume of the neighboring cortical bone were adequate, and the augmented edentulous space was subsequently restored with a functional endosseous implant . The success seen in these 2 sites would seem to confirm the assumption that size and location of myospherulosis defects are critical factors in obtaining a successful clinical result in implant patients. Joint Bone Spine, 2001 Dec, 68(6), 504 - 9 Management of nontuberculous infectious discitis . treatments used in 110 patients admitted to 12 teaching hospitals in France; Legrand E et al.; The optimal management of pyogenic discitis is not agreed on . No randomized clinical trials of short-course or oral antibiotic regimens have been published to date . To shed light on this issue, we reviewed the management of patients admitted for pyogenic discitis to one of 12 networked rheumatology departments . In this cross-sectional observational study, each department included the first ten patients admitted starting in January 1997 for treatment of pyogenic discitis . One hundred ten patients met the inclusion criteria, 67 men and 43 women, with a mean age of 60.6 +/- 13.7 years (range, 17-86 years) . Mean time from symptom onset to diagnosis was 39.6 +/- 39.8 days (range, 24 h-240 days) . Blood cultures were positive in 47.3% of patients, and the percutaneous discal and vertebral biopsy in 63.6% of cases; these two investigations identified the causative organism in 79 cases (72.8%) . Mean duration of the rheumatology department stay was 31.3 +/- 14.1 days (range, 4-78 days) . Antibiotics were given intravenously to 103 (93.6%) patients, for a mean of 25.5 +/- 17.6 days (range, 4-124 days); duration of intravenous antibiotic therapy was longer than 4 weeks in 36.5% of patients . Only seven (6.4%) patients received primary oral antibiotics with no parenteral antibiotics . One hundred patients were given oral antibiotics at the same time as and after intravenous antibiotics, for a mean duration of 87.2 +/- 43.6 day (range, 20-278 days); Bracing was used in 98 (89.1%) patients . Although antibiotic selection was rational and in agreement with current recommendations, wide differences were noted across centers regarding intravenous treatment duration, hospital stay duration, and total treatment duration. Rinsho Shinkeigaku, 2001 Jul, 41(7), 435 - 7 {A case with bacterial meningitis caused by cerebrospinal fluid rhinorrhea 22 years after head trauma}; Tokisato K et al.; A 38-year-old man with past history of head injury at the age of 16 years was admitted to our hospital in April, 2000 because of bacterial meningitis . At the end of March 2000, he experienced massive cerebrospinal fluid (CSF) rhinorrhea when he rested in bed, and subsequently he developed high-grade fever, headache, and nuchal stiffness in 2 weeks . His symptoms and signs improved with the antibiotic therapy alone . He had no recurrence of meningitis since then . A defect of his right skull base was clarified by 3D-CT, and multiplanar reconstruction (MPR)-CT . MRI brain scan showed the dislocation of the right frontal lobe into the ipsilateral anterior ethmoidal sinus . The diagnosis of CSF rhinorrhea and bacterial meningoencephalitis were made according to his clinical manifestations and neuroradiological studies including 3D-CT, MPR-CT and MRI brain scans . These imaging modalities, which described his head anatomy precisely, helped us to clarify the cause of his illness . When CSF rhinorrhea is present, it is important to take detailed past history of head trauma, even if the event occurred more than 20 years previously. Clin Infect Dis, 2002 Mar 1, 34(5), E28 - 31 Epub 2002 Jan 23. Changing clinical presentation of Q fever endocarditis; Houpikian P et al.; Fifteen cases of Q fever endocarditis that occurred in 1999-2000 in southern France are described and compared with 15 cases from the same area reported in 1987 . Significant decreases were found in the prevalences of heart failure, hepatomegaly, inflammatory syndrome, anemia, leukopenia, and abnormal liver function test results in patients who had Q fever endocarditis after 1997 . This was probably the result of a reduction in the delay before diagnosis of the disease and of the use of novel, effective antibiotic regimens. No Shinkei Geka, 2002 Jan, 30(1), 73 - 8 {A case of multiple mycotic intracranial aneurysms presenting with subdural hematoma}; Matsuda T et al.; A patient with subdural hematoma associated with multiple mycotic intracranial aneurysms is reported . A 22-year-old woman presented with headache and disturbance of consciousness . A CT showed subdural hematoma at the tentrium and the left cerebral convexity . Conservative treatment and was used and she was discharged 10 days later . However, follow-up CT demonstrated a parenchymal hematoma in the right posterior temporal lobe . Cerebral angiography demonstrated a large right posterior cerebral aneurysm and multiple right middle cerebral aneurysms . A cardiac ultrasonography showed a verruca at the mitral valve . The posterior cerebral aneurysms increased in size and one new middle cerebral aneurysm appeared at follow-up angiography one week later . Endovascular treatment with coils was applied for the right posterior cerebral aneurysm, and others were treated with antibiotic therapy under serial observation, using MR angiography . She was discharged without any symptoms two months after embolization . Follow-up angiography at one year after embolization showed disappearance of the aneurysms . The possibility of mycotic aneurysm should be considered in the differential diagnosis of non-traumatic acute subdural hematoma. Curr Opin Crit Care, 2001 Dec, 7(6), 464 - 8 Protocols and guidelines in critical care: development and implementation; Hammond JJ; Variation in clinical management has been associated with suboptimal outcomes and increased costs . Guidelines, protocols, and clinical pathways have evolved as a strategy to standardize care, principally by limiting variation, thereby reducing complications, decreasing length of stay and improving outcomes . However, the nature of critical care makes it difficult to conduct blinded, randomized, and controlled clinical trials, the specific type of science required for evidenced-based medicine and guideline development . Areas in which ICU-based guidelines have been successful include, among others, sedation and neuromuscular blockade use, ventilator management, antibiotic selection, and vascular surgical interventions. J Int Med Res, 2001 Nov-Dec, 29(6), 537 - 40 Concentration of roxithromycin in the lesions of acne vulgaris; Akamatsu H et al.; Roxithromycin, a macrolide antibiotic, is used in the treatment of acne vulgaris, although there have been no reports on its concentration in lesions when administered orally . We investigated the concentration of roxithromycin in acne vulgaris lesions in five patients who received 150 mg roxithromycin orally twice daily for 2 weeks . The mean concentration of roxithromycin in the lesions was 0.54 microgram/ml . These results suggest that roxithromycin accumulates at therapeutic levels in the pilosebaceous system. J Int Med Res, 2001 Nov-Dec, 29(6), 523 - 7 Effects of roxithromycin on adhesion molecules expressed on endothelial cells of the dermal microvasculature; Akamatsu H et al.; The objective of the study was to investigate the pharmacological action of roxithromycin, an oral macrolide antibiotic . The effects of roxithromycin on the cytokine-induced expression of endothelial leukocyte adhesion molecule (E-selectin) and intracellular adhesion molecule (ICAM)-1 on endothelial cells of the dermal microvasculature were investigated in vitro using flow cytometry . Roxithromycin at a concentration of 0.5 microgram/ml, which is lower than the therapeutic plasma concentration (ordinary daily dose, 150-300 mg), significantly inhibited the expression of E-selectin and ICAM-1 on endothelial cells of the dermal microvasculature induced by tumour necrosis factor-alpha . We conclude that roxithromycin may exert its anti-inflammatory action by inhibition of the in vivo expression of adhesion molecules on dermal microvascular endothelial cells. Pharmacology, 2002 Feb, 64(2), 84 - 90 Effect of 17beta-estradiol on intracellular Ca(2+) levels in renal tubular cells; Chen WC et al.; The effect of 17beta-estradiol on intracellular Ca(2+) concentrations ({Ca(2+)}(i)) in Madin Darby canine kidney cells was investigated by using the fluorescent dye fura-2 . 17Beta-estradiol (5-100 micromol/l) induced instantaneous increases in {Ca(2+)}(i) in a concentration-dependent manner . Ca(2+) removal inhibited 45 +/- 15% of the Ca(2+) signal . In Ca(2+)-free medium, pretreatment with 50 micromol/l 17beta-estradiol abolished the {Ca(2+)}(i) increases induced by 2 micromol/l carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler), 1 micromol/l thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) and 50 micromol/l brefeldin A (an antibiotic which disperses the Golgi complex), but pretreatment with brefeldin A, CCCP and thapsigargin only partly inhibited the 17beta-estradiol-induced {Ca(2+)}(i) signal . Adding 3 mmol/l Ca(2+) increased {Ca(2+)}(i) in cells pretreated with 5-100 micromol/l 17beta-estradiol in Ca(2+)-free medium . Pretreatment with 1 micromol/l U73122 to abolish the formation of inositol-1,4,5-trisphosphate inhibited 50% of the Ca(2+) release induced by 50 micromol/l 17beta-estradiol . 17Beta-estradiol (20 micromol/l) also increased {Ca(2+)}(i) in human bladder cancer cells and prostate cancer cells . Collectively, this study shows that 17beta-estradiol evoked a significant internal Ca(2+) release and external Ca(2+) entry possibly in a nongenomic manner . Pediatr Pulmonol, 2002 Feb, 33(2), 162 - 4 Congenital bronchoesophageal fistula and tracheoesophageal fistula with esophageal atresia; Anuntaseree W et al.; A case of initial esophageal atresia and tracheoesophageal fistula in a female newborn, later complicated by pneumonia and a second bronchoesophageal fistula, is reported . She was treated surgically by closure of the tracheoesophageal fistula and by end-to-end esophago-esophageal anastomosis . An esophagram at 1 month of age was normal . Three months later she developed severe, persistent right lower lobe pneumonia that required intensive antibiotic therapy and respiratory support . Esophagography was repeated and revealed a second fistula between the right main-stem bronchus and the lower esophagus . The bronchoesophageal fistula was repaired, and a right lower lobectomy was performed . Postoperative recovery was uncomplicated . Histologic examination indicated that the fistula was congenital in origin . To the best of our knowledge, this is the first reported case of a congenital bronchoesophageal fistula coexisting with a tracheoesophageal fistula and esophageal atresia . J Vasc Surg, 2002 Jan, 35(1), 80 - 6 Technical details with the use of cryopreserved arterial allografts for aortic infection: influence on early and midterm mortality; Vogt PR et al.; PURPOSE: In situ repair with cryopreserved vascular allografts improves the results in the surgical treatment of aortic infection . This study evaluated the technical pitfalls with the use of allografts that influence early and midterm mortality . METHODS: Between 1990 and 1999, 49 patients, 21 (43%) with a mycotic aneurysm and 28 (57%) with a prosthetic graft infection of the thoracic and abdominal aorta including pelvic and groin vessels, underwent in situ repair with cryopreserved arterial allografts . Seventeen patients (35%) had aortobronchial, aortoesophageal, or aortoenteric fistulas . RESULTS: Allograft-related technical problems occurred in eight patients (16%) in this series, and they included: intraoperative rupture caused by allograft friability; allograftenteric fistula from ligated allograft side branches rupturing 8, 18, and 48 months after implantation; anastomotic failure caused by inappropriate mechanical stress; anastomotic stricture after partial replacement of infected prosthetic grafts; allograft failure caused by inappropriate wound drainage; and recurrence of infection after inappropriate duration of antifungal treatment . Seven of the eight technical problems (87%) occurred in the first 10 patients (80%) in this series . There was one technical failure in the remaining 39 patients (2.6%; P =.0002) because of various technical adaptations, such as critical selection of allografts, use of allograft strips supporting large anastomoses, sealing with antibiotic-impregnated fibrin glue, and change in technique of allograft si