Antibiotics

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 side-branch ligature . The 30-day mortality rate was 6% for the whole series; however, it was 2.6% for last 39 patients, with no recurrence of infection or allograft-related late death . CONCLUSIONS: In situ repair with cryopreserved arterial allografts achieves excellent early and late results in the treatment of aortic infection . However, distinct allograft-related technical problems had to be overcome to improve the outcome of patients with major vascular infections.

J Antimicrob Chemother, 2002 Feb, 49 Suppl 1, 75 - 80
Prophylaxis and treatment of patients with aspergillosis: an overview, including the Royal Melbourne Hospital experience; Grigg A; Patients receiving allogeneic bone marrow transplants are at risk of developing Aspergillus infections . The pre-transplant risk factors for the development of invasive disease include prolonged neutropenia, colonization with Aspergillus sp . or a prior history of fungal infection . Post-transplant risk factors include severe graft-versus-host disease with concomitant high-dose corticosteroid therapy, and colonization with Aspergillus sp . The antifungal prophylaxis of selected high-risk pre-transplant patients at the Royal Melbourne Hospital includes granulocyte transfusions and AmBisome . In high-risk patients post-engraftment, prophylaxis consists of oral itraconazole, or if it cannot be tolerated, AmBisome . Antifungal prophylaxis is discontinued upon resolution of neutropenia, when prednisolone dose falls below 10 mg/day or when Aspergillus colonization disappears . Following this regimen, there has been only one death due to fungal infection in over 80 consecutive allograft patients . This patient was infected with an amphotericin B-resistant organism.

J Antimicrob Chemother, 2002 Feb, 49 Suppl 1, 51 - 5
Ten years' experience with liposomal amphotericin B in transplant recipients at Huddinge University Hospital; Ringden O; Our substantial experience in several trials with AmBisome in adult and paediatric patients undergoing transplantation has shown this formulation of amphotericin B to be safe and effective in therapeutic and prophylactic use . AmBisome has shown a significant reduction in fungal colonization and invasive Candida infections compared with placebo in a prospective, double-blind study in bone marrow transplantation, and eradication of invasive fungal infections in 86% of 14 children undergoing bone marrow transplantation . The main side effects of AmBisome use are elevations in serum potassium and creatinine, but these lead to very few withdrawals from treatment . Compared with conventional amphotericin B, AmBisome is very expensive, but its much improved safety profile and proven efficacy make it an excellent agent for management of invasive fungal disease in transplant recipients.

Prim Dent Care, 2001 Oct, 8(4), 145 - 8
Advances in surgical dentistry; Patel D et al.; The introduction of the specialty of surgical dentistry is an advance in itself and has far-reaching implications for the future . Surgical specialists will have a significant impact on the provision and resources of surgical dental services . This paper explores recent developments within the field.

J Endovasc Ther, 2001 Dec, 8(6), 597 - 601
Repair of secondary aortoesophageal fistula by endoluminal stent-grafting; Bond SE et al.; PURPOSE: To describe a case of secondary aortoesophageal fistula that was treated with an endoluminal stent-graft . CASE REPORT: A 58-year-old woman presented with hematemesis and melena . In 1974 she had an interposition graft repair of an aortic transection sustained during a traffic accident . At the examination in 1998, angiography demonstrated a mechanical disruption of the proximal anastomosis forming an aortoesophageal fistula . A 28-mm x 3.75-cm AneuRx stent-graft was introduced via a right femoral arteriotomy and deployed across the defect . Follow-up CT scans at 18 months showed exclusion of the false aneurysm with no evidence of infection; the patient remains well at >2 years after stent-graft implantation . CONCLUSIONS: Endoluminal repair can be successful in achieving a satisfactory midterm outcome in cases of secondary aortoesophageal fistula.

Dis Aquat Organ, 2001 Oct 29, 47(1), 49 - 55
Morphology and biology of parasite responsible for scuticociliatosis of cultured olive flounder Paralichthys olivaceus; Jee BY et al.; Based on the arrangement and shape of the buccal structure, scuticociliates isolated from cultured olive flounder Paralichthys olivaceus belonged to the family Uronematidae and showed many characteristics of Uronema marinum . There was variation in the morphometry of clinical isolates taken from different organs of infected flounder . However, the isolates did not show any significant difference in morphometry under cultured conditions . The ciliates were easily maintained in in vitro medium to which antibiotic agents had been added and which had been enriched with the raw brain tissue of a healthy olive flounder . The ciliates propagated in a wide range of both temperature (6 to 30 degrees C) and salinity (10 to 35 ppt).

Trans Am Ophthalmol Soc, 2001, 99, 159 - 68; discussion 168-70
Surface keratopathy after penetrating keratoplasty; Feiz V et al.; PURPOSE: To determine the type and prevalence of epithelial abnormalities in the intermediate postoperative period after penetrating keratoplasty and to define the donor and recipient variables that influence the status of the graft epithelium . DESIGN: Prospective cohort study . METHODS: We prospectively followed the clinical course of 80 patients after penetrating keratoplasty . We monitored the status of the corneal epithelium for 3 months after surgery using slit-lamp biomicroscopy and fluorescein staining of the epithelium . Donor characteristics, recipient preoperative and postoperative variables, and postoperative medications were recorded . Epithelial abnormalities were analyzed against these variables by using univariate and combined statistical models to determine the impact of each variable on postoperative epithelial pathology . Main outcome measures included punctate keratopathy, macro-epithelial defects, hurricane keratopathy, rim defects, and filamentary keratopathy . RESULTS: Sixty-three percent of all patient visits demonstrated punctate epithelial keratopathy (PEK) . Hurricane keratopathy (51%) and filamentary keratopathy (14%) constituted the next most commonly observed abnormalities . Older recipient age and the use of topical antibiotics were associated with a higher prevalence of punctate epithelial keratopathy . The odds ratio (OR) for a 1-year increase in age is 1.0276 (95% CI, 1.1013-1.0442), and the OR for using topical antibiotics is 6.9028 (95% CI, 3.1506-15.1239) . Use of topical ofloxacin and increased time after surgery were associated with lower prevalence of punctate keratopathy; ORs were 0.9806 (95% CI, 0.9736-0.9876) and 0.3662 (95% CI, 0.1688-0.7943), respectively . Decreased corneal sensation and the presence of anterior blepharitis preoperatively were associated with an increase in hurricane keratopathy; ORs were 8.8265 (CI, 2.3837-32.6835) and 3.2815 (CI, 1.7388-6.1931), respectively . Total storage time for the donor material was also associated with an increased prevalence of hurricane keratopathy (OR, 1.0316; CI, 1.0052-1.0220) . Patients with rim defects and macro-epithelial defects were more likely to have antibiotic and topical lubrication prescribed . No specific variable was found to have a significant association with filamentary keratopathy, except possibly for death-to-preservation time, which had a P value of .0587 . CONCLUSIONS: Surface keratopathy is one of the most common complications of keratoplasty . Our study demonstrates that older age, preoperative lid disease, and decreased preoperative corneal sensation appear to increase the probability of clinically significant epithelial surface abnormalities after keratoplasty . Recognition of these risk factors in advance of surgery will alert the surgeon to the need for appropriate management.

Cancer Radiother, 2001 Dec, 5(6), 770 - 86
{Standards, Options, and Recommendations for brachytherapy in patients with prostate cancer: efficacy and toxicity}; Pommier P et al.; CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies . Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients . The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts . Draft guidelines are produced, then validated by specialists in cancer care delivery . OBJECTIVES: Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project . METHODS: The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts . Available data were collected by a search of Medline and lists selected by experts in the group . A first draft of the guidelines was written, they validated by independent reviewers . RESULTS: The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L . 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis . 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation) . 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection . 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported . The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.

Arch Microbiol, 2001 Dec, 177(1), 11 - 9 Epub 2001 Oct 03.
Assay of ATP in intact cells of the facultative phototroph Rhodobacter capsulatus expressing recombinant firefly luciferase; Di Tomaso G et al.; This study reports on the construction, calibration and use of recombinant cells of Rhodobacter capsulatus expressing the luciferase gene of the North American firefly Photinus pyralis to detect, by bioluminescence, variations of endogenous ATP levels under various physiological conditions . We show that the antibiotic polymyxin B allows luciferin to rapidly move into cell cytosol, but does not make external ATP freely accessible to intracellular luciferase . Notably, in toluene:ethanol-permeabilized cells, the apparent K(mATP) for luciferase (50 microM) is similar to that measured in soluble cell fractions . This finding limits the applicability of the firefly luciferase for monitoring intracellular maximal ATP concentration because dark/aerobic-grown recombinant cells of Rba . capsulatus contain approximately 1.3-2.6+/-0.5 mM ATP . Therefore, the effects of chemical and physical factors such as oxygen, light, carbonyl cyanide m-chlorophenyl hydrazone and antimycin A on ATP synthesis were examined in cells subjected to different starvation periods to reduce the endogenous ATP pool below the luciferase ATP saturation level (< or =0.2 mM) . We conclude that the amount of endogenous ATP generated by light is maximal in the presence of oxygen, which is required to optimize the membrane redox poise.

Antimicrob Agents Chemother, 2002 Feb, 46(2), 575 - 7
Stability of new carbapenem DA-1131 to renal dipeptidase (dehydropeptidase I); Park SW et al.; The stability of DA-1131 to renal dipeptidase (RDPase) (EC 3.4.13.19) was compared with that of imipenem and meropenem by V(max)/K(m) ratios as an index of the enzyme's preference for substrates . Our results showed a decreasing order of imipenem (6.24), meropenem (2.41), and DA-1131 (1.39) . The biochemical evaluation of DA-1131 as the least preferred substrate of RDPase suggests its potential use as a novel beta-lactam antibiotic which may be usable without coadministration of RDPase inhibitors once its clinical suitability is proven.

J Urol, 2002 Feb, 167(2 Pt 1), 566 - 70
The procedure of transrectal ultrasound guided biopsy of the prostate: a survey of patient preparation and biopsy technique; Davis M et al.; PURPOSE: We surveyed urologists in community and academic practice regarding their standard approach to patient preparation and their technique of transrectal ultrasound guided prostate biopsy . MATERIALS AND METHODS: We mailed 110 surveys to community urologists in Florida and urological oncologists at academic centers across the United States . Responses were calculated per group . RESULTS: Of the 88 respondents 34% were at academic centers and 66% were community urologists . Overall 79% of respondents prescribe an enema in preparation for biopsy, 81% administer an oral fluoroquinolone before biopsy, 50% give some type of analgesia, usually an oral agent, 63% obtain 8 or more cores per biopsy session, 36% biopsy the lateral and midline locations, and 83% do not use prostate specific antigen density to plan the biopsy strategy . CONCLUSIONS: The majority of urologists who responded to our survey ask their patients to use an enema in preparation for a transrectal biopsy procedure, prescribe an oral antibiotic and administer some type of analgesia . Few urologists administer a periprostatic nerve block . The majority obtain at least 8 biopsies and only 17% perform sextant biopsy . Some of these practices are not consistent with the literature . This survey provides insight into the practice patterns of urologists in regard to one of the most commonly performed office procedures.

Rev Esp Anestesiol Reanim, 2001 Nov, 48(9), 423 - 33
{Anesthesia for the patient with cancer}; Monedero P et al.; Surgery and radiotherapy provide the basis for local and regional control of cancer . The cancer patient has special characteristics that have implications for anesthesia . Tumors may involve the airways and affect ventilation, hemodynamics and intracranial pressure . Remote tumors can occur in endocrine cancer and in paraneoplastic syndromes . Other systemic complications of the cancer patient include hemostatic changes, immunosuppressant anemia and altered metabolism . Radiotherapy causes changes with anesthetic implications when treatment is directed at the head and neck, mediastinum, lung or surgical area . Chemotherapy is associated with non-specific toxic effects such as mucositis, aplasia and immunosuppression, alopecia and vascular injury; in addition, each chemical has other more specific toxic effects . Chemicals that are toxic for the heart and lungs have the greatest implications for anesthesia . Preoperative assessment should ascertain the effects caused by both the tumor and its treatment . Preparation for surgery includes improving nutrition and possibly inserting a venous port . Management during surgery depends on type of intervention and the patient's physical status, as they will determine the need for invasive monitoring and vessel access . The patient can be given antiemetic and antithrombotic prophylaxis . Important issues in postoperative care are the need for adequate analgesia; provision of early nutrition; antibiotic, antithrombotic and antiemetic prophylaxis; and prevention of ulcers caused by pressure.

Emerg Infect Dis, 2001 Sep-Oct, 7(5), 828 - 31
Intraoperative redosing of cefazolin and risk for surgical site infection in cardiac surgery; Zanetti G et al.; Intraoperative redosing of prophylactic antibiotics is recommended for prolonged surgical procedures, although its efficacy has not been assessed . We retrospectively compared the risk of surgical site infections in 1,548 patients who underwent cardiac surgery lasting >240 min after preoperative administration of cefazolin prophylaxis . The overall risk of surgical site infection was similar among patients with (43 {9.4%} of 459) and without (101 {9.3%} of 1,089) intraoperative redosing (odds ratio {OR} 1.01, 95% confidence interval {CI} 0.70-1.47) . However, redosing was beneficial in procedures lasting >400 min: infection occurred in 14 (7.7%) of 182 patients with redosing and in 32 (16.0%) of 200 patients without (adjusted OR 0.44, 95% CI 0.23-0.86) . Intraoperative redosing of cefazolin was associated with a 16% reduction in the overall risk for surgical site infection after cardiac surgery, including procedures lasting <240 min.

Biochemistry, 2002 Jan 22, 41(3), 897 - 905
Delocalized electronic structure of the thiol sulfur substantially prevents nucleic acid damage induced by neocarzinostatin; Kuo HM et al.; Neocarzinostatin is a potent antitumor antibiotic and is a prodrug, which induces genome damage after activation by a thiol . The prodrug is stored as a protein-bound chromophore that contains an enediyne nucleus . A thiolate attack on the chromophore cyclizes the nucleus and produces radicals that abstract hydrogen from DNA . Because thiol is the only cofactor in the vital activation process, the structure of the thiol plays an important role in the activity of the drug . Here we systematically examine the effect of the electronic structure of some thiols on the efficiency of the drug, and compare particularly aromatic with aliphatic thiols . The values of drug-induced base release from DNA are remarkably different between thiophenol (3.6%) and benzyl mercaptan (12.5%), the activity of which is comparable with those of aliphatic thiols . Cleavage results determined by DNA electrophoresis are consistent with the results of base release; they show that the total number of DNA lesions is more than 3-fold lower for thiophenol than for aliphatic thiols or benzyl mercaptan . We conclude that among aromatic thiols, only those that have delocalized thiol sulfur electrons can substantially reduce the DNA cleavage activity . This result suggests that the effect of an aromatic ring arises from an inductive effect imposed on the thiol sulfur electron through pi-resonance rather than through effects such as aromatic stacking, steric hindrance, or hydrophobic interaction . Replacing thiophenol with substituted derivatives with electron-releasing or -withdrawing groups changes the drug activity and supports the important role of the electronic structure of the thiol sulfur in determining the drug activity.

J Vet Med Sci, 2001 Dec, 63(12), 1263 - 9
Bronchoalveolar lavage for the diagnosis and treatment of pneumonia associated with transport in Thoroughbred racehorses; Ito S et al.; To evaluate a hypothese that use of bronchoalveolar lavage (BAL) for early treatment of pneumonia would improve their prognosis by reducing bacterial numbers and excessive numbers of neutrophils in the lung, initial experiences with BAL in the diagnosis and treatment of pneumonia were performed in 36 racehorses that became ill within 24 hr of long distance travel (1,200-1,600 km, 26-32 hr) by road . Comparisons were made of the outcomes of the 36 horses and those of 42 horses (81.0% recovered, 50.0% returned to racing) treated for transport associated pneumonia without BAL . The total amount of BAL fluid injected during hospitalization varied from 700 to 3,700 ml and the duration of antibiotic treatments ranged from 5 to 40 days . Clinical symptoms after lavages showed good results with no side effects . None of the horses required thoracic drainage . Horses treated with BAL required shorter period of antibiotic therapy, a greater percentage recovered (100%, 36/36) and a greater percentage returned to racing (77.8%, 28/36) . Eight (22.2%) never raced because of lameness or other considerations.

J UOEH, 2001 Dec 1, 23(4), 437 - 41
{A case of acute focal bacterial nephritis}; Yamada Y et al.; We report a case of acute focal bacterial nephritis (AFBN) . A 30-year-old female patient visited Kyushu Rosai hospital with complaints of right flank pain and a fever of 3 days duration . She was immediately admitted, but still suffered from flank pain after 3 days of antibiotic therapy . Abdominal CT scan detected a focal mass lesion in the mid portion of the right kidney . Her clinical symptoms improved after 7 days of chemotherapy, and she was discharged . The mass lesion in the kidney disappeared after one month, she remained free of symptoms, and renal function was normal when followed up nineteen months later.

J Reprod Med, 2001 Dec, 46(12), 1071 - 7
39-day delay in delivery of twins . A case report; Benden D et al.; BACKGROUND: Delayed delivery is a rare occurrence in the literature despite advances in reproductive technology and increasing numbers of multiple gestations . CASE: A 30-year-old woman, gravida 2, para 0010, presented at 23 weeks and 3 days' gestation with a twin pregnancy . An interval of 39 days was achieved between delivery of the first and second fetus with aggressive tocolysis and antibiotic therapy . Follow-up at three years revealed the second twin to be a fully functioning boy . CONCLUSION: Forty citations in the literature have examined delayed delivery . With careful patient selection and thorough patient counseling, delayed delivery offers a safe and beneficial management option for selected multiple gestations.

Postgrad Med, 2001 Aug, 110(2), 69 - 72, 75-6, 82-3, passim
Valvular heart disease and pregnancy . A high index of suspicion is important to reduce risks; Prasad AK et al.; Pregnant women who have valvular disease represent a major challenge for physicians involved in their care . Careful history taking and physical examination, along with a judicious use of diagnostic tools (mainly echocardiography), can lead to better management and ultimately to excellent outcomes for both mother and baby.

Chemotherapy, 2001 Dec, 47(6), 387 - 95
Comparative pharmacokinetics of three preparations of the new antifungal SPK-843; Bruzzese T et al.; The pharmacokinetics and tissue distribution of three preparations of SPK-843 (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate), a new polyene antibiotic with a heptaene structure, were compared in rats after a single 1.25 mg/kg intravenous administration . Blood and tissue samples were obtained at 0.25-96 h after injection . The serum pharmacokinetics of the three dosage forms of the antibiotic, A (5% glucose solution), B (10% lipid emulsion at pH 5.3) and C (10% lipid emulsion at pH 7.5), did not show large differences, the half-lives being 22.2, 26.5 and 23.2 h and the AUC(0-infinity) 35.5, 40 and 44.8 microg.h.ml(-1) for preparations A, B and C, respectively . The tissue uptake of the two lipid-based preparations, particularly the spleen uptake, was greater than that of the glucose preparation, suggesting an active role of the lipid vehicle in tissue distribution .

Arch Pediatr Adolesc Med, 2002 Jan, 156(1), 41 - 3
Effect of rapid diagnosis of influenza virus type a on the emergency department management of febrile infants and toddlers; Sharma V et al.; BACKGROUND: Evidence shows that the rapid detection of influenza using an enzyme-linked immunosorbent assay decreases antibiotic use in the treatment of pediatric patients . To our knowledge, the effect on other diagnostic testing in an emergency department (ED) has not been examined . OBJECTIVE: To determine the effect of rapid diagnosis of influenza virus type A on the clinical management of febrile infants and toddlers in a pediatric ED at an urban children's hospital . MATERIALS AND METHODS: A retrospective review of ED records from an electronic database was performed . All children 2 to 24 months of age, with a temperature higher than 39 degrees C who had a positive influenza virus type A test result using an enzyme-linked immunosorbent assay from November 1, 1998, through April 30, 2000 (n = 72), were included in this study . Two groups were compared-those who had positive test results reported before discharge from the ED (early diagnosis) and those who had positive test results after discharge (late diagnosis) . RESULTS: Forty-seven patients (65%) were in the early diagnosis group and 25 (35%) in the late diagnosis group . The groups were similar for age, temperature, and triage category . Fewer patients in the early diagnosis group received ceftriaxone sodium compared with those in the late diagnosis group (2% vs 24%, P =.006); there were fewer urinalyses (2% vs 24%, P =.006) and complete blood cell counts performed (17% vs 44%, P =.02) . CONCLUSIONS: Rapid confirmation of influenza virus type A infection seems to decrease ancillary tests and antibiotic use in febrile infants and toddlers in the ED . A prospective study with a larger group is needed to confirm these findings.

Eur J Biochem, 2002 Jan, 269(1), 100 - 9
Amphibian peptides that inhibit neuronal nitric oxide synthase . Isolation of lesuerin from the skin secretion of the Australian Stony Creek frog Litoria lesueuri; Doyle J et al.; Two neuropeptides have been isolated and identified from the secretions of the skin glands of the Stony Creek Frog Litoria lesueuri . The first of these, the known neuropeptide caerulein 1.1, is a common constituent of anuran skin secretions, and has the sequence pEQY(SO3)TGWMDF-NH2 . This neuropeptide is smooth muscle active, an analgaesic more potent than morphine and is also thought to be a hormone . The second neuropeptide, a new peptide, has been named lesueurin and has the primary structure GLLDILKKVGKVA-NH2 . Lesueurin shows no significant antibiotic or anticancer activity, but inhibits the formation of the ubiquitous chemical messenger nitric oxide from neuronal nitric oxide synthase (nNOS) at IC(50) (16.2 microm), and is the first amphibian peptide reported to show inhibition of nNOS . As a consequence of this activity, we have tested other peptides previously isolated from Australian amphibians for nNOS inhibition . There are three groups of peptides that inhibit nNOS (IC(50) at microm concentrations): these are (a) the citropin/aurein type peptides (of which lesueurin is a member), e.g . citropin 1.1 (GLFDVIKKVASVIGGL-NH(2)) (8.2 microm); (b) the frenatin type peptides, e.g . frenatin 3 (GLMSVLGHAVGNVLG GLFKPK-OH) (6.8 microm); and (c) the caerin 1 peptides, e.g . caerin 1.8 (GLFGVLGSIAKHLLPHVVPVIAEKL-NH(2)) (1.7 microm) . From Lineweaver-Burk plots, the mechanism of inhibition is revealed as noncompetitive with respect to the nNOS substrate arginine . When the nNOS inhibition tests with the three peptides outlined above were carried out in the presence of increasing concentrations of Ca(2+) calmodulin, the inhibition dropped by approximately 50% in each case . In addition, these peptides also inhibit the activity of calcineurin, another enzyme that requires the presence of the regulatory protein Ca(2+) calmodulin . It is proposed that the amphibian peptides inhibit nNOS by interacting with Ca(2+)calmodulin, and as a consequence, blocks the attachment of this protein to the calmodulin domain of nNOS.

Perit Dial Int, 2001 Nov-Dec, 21(6), 587 - 94
Pharmacokinetics of intraperitoneal cefazolin and gentamicin in empiric therapy of peritonitis in continuous ambulatory peritoneal dialysis patients; Tosukhowong T et al.; OBJECTIVE: The aim of this study was to measure and evaluate the appropriateness of the actual concentrations of serum and dialysate cefazolin and gentamicin in Thai continuous ambulatory peritoneal dialysis (CAPD) patients treated following the International Society for Peritoneal Dialysis (ISPD) 1996 recommendations for the empiric therapy of CAPD-related peritonitis . DESIGN: Prospective and descriptive study . SETTING: Institutional level of clinical care . PATIENTS: CAPD-related peritonitis patients were diagnosed by dialysate effluent white cell count of more than 100/mm3 and polymorphonuclear leukocytes of at least 50% . There were 18 patients, all at least 15 years of age, entered; all completed the study . INTERVENTION: In accordance with the ISPD 1996 recommendations, the antibiotic regimen included continuous intraperitoneal (IP) cefazolin and once-daily IP aminoglycoside . Cefazolin was administered as loading and continuous maintenance doses of 500 and 125 mg/L dialysate, respectively . Gentamicin, 0.6 mg/kg body weight, was given IP once daily . Duration of treatment was 120 hours . MAIN OUTCOME MEASURES: Serum and dialysate effluent samples of the 18 CAPD patients with peritonitis were measured and used for the synthesis of pharmacokinetic equations that could predict drug concentrations at any treatment time . RESULTS: Following administration according to the ISPD 1996 treatment recommendations, serum cefazolin reached levels higher than the recommended levels (8 microg/mL) at 3.3 minutes after drug administration, and persisted through the 5-day duration of the study . Dialysate cefazolin levels during the studied period also were persistently higher than the recommended values . The peak serum gentamicin levels were lower than the suggested values of 4 microg/mL, whereas the trough serum gentamicin levels were higher than the minimal toxic concentrations (2 microg/mL) . Dialysate gentamicin levels were higher than therapeutic concentrations for only 4.75 hours in each day . It was difficult, using pharmacokinetic studies, to adjust the dosage regimen of gentamicin to achieve appropriately therapeutic levels in both serum and dialysate . CONCLUSIONS: The ISPD 1996 recommended dosage of continuous IP cefazolin could be appropriate for the treatment of CAPD-related peritonitis . Once-daily IP gentamicin administration, however, has less therapeutic benefit and should be re-evaluated.

Zhonghua Fu Chan Ke Za Zhi, 2001 Mar, 36(3), 133 - 6
{Transcatheter arterial embolization in intractable postpartum hemorrhage}; Chen C et al.; OBJECTIVE: To asses the value of transcatheter arterial embolization treatment in intractable postpartum hemorrhage . METHODS: Fourteen patients of postpartum hemorrhage failed to the drugs treatment were performed transcatheter arterial embolization (TAE) . Superselective catheterization to the bilateral uterial arteries or anterior branches of internal iliac arteries was carried out after intubation to single-side femoral artery by Seldinger's technique . When the catheter tip was proved in right place by digital substraction angiography (DSA) techniques, antibiotic solution was poured into arteries and then the arterial embolization with gelfoam particles was followed . RESULTS: All the patients were performed TAE successfully . The duration of TAE was 30-50 minutes {mean (41.8 +/- 6.4) minutes} . Bleeding was found in DSA mostly as diffuse intrauterine flow outward sign from one side or both side of uterial artery branches . After one time of TAE, the vaginal bleeding of all patients was stopped in 3-10 minutes {mean (6.1 +/- 3.6) minutes} . The follow-up showed that all patients had normal menstrual periods in 2-60 months and no serious complications were found . CONCLUSION: With the characteristic of fast homeostasis and less complications, TAE was proved to be an effective method for intractable postpartum hemorrhage.

J Med Virol, 2002 Feb, 66(2), 224 - 8
Enteroviral meningitis in Northern Jordan: prevalence and association with clinical findings; Meqdam MM et al.; During the summer-autumn of 1999, 390 specimens of cerebrospinal fluid were taken from infants and children younger than 15 years of age . They were suspected of having meningitis and were admitted to Princess Rahma Hospital, Northern Jordan . They were investigated for the presence of enteroviruses using shell vial culture and indirect immunofluorescence assays . Most cases (46.9%) occurred in children younger than 1 year of age in which males represented 71.9% . The common symptoms were fever, vomiting, and headache . Enteroviruses were isolated from 32 (8.2%) cases, coxsackievirus B types 2, 4, and 5 from 15 (46.9%) cases, and echovirus 9 (31.3%) was the most common identified serotype . The virus isolation rate was directly proportional to the number of leukocytes in the cerebrospinal fluid . However, enteroviral isolation was demonstrated in 4 (12.5%) of 32 cerebrospinal fluid specimens without pleocytosis . Leukocyte differential count revealed a predominance of polymorphonuclear cells in 71.4% of the cases . Hospitalization ranged from 1 day to 25 days with a mean of 7 days . The majority of enterovirus-infected patients (88.9%) were treated with at least one type of antibiotic . These results emphasize the importance of shell vial culture assay for diagnosing enteroviruses, especially in laboratories that do not have access to advanced techniques such as polymerase chain reaction .

Eur J Gastroenterol Hepatol, 2002 Jan, 14(1), 81 - 3
Spontaneous bacterial peritonitis caused by quinolone-resistant Escherichia coli: could steroid therapy play a role?
Cereto F, Genesca J, Smithson A, Gonzalez A, Moreno G, del Valle Ortiz O, Esteban R, Guardia J.
Prophylaxis with norfloxacin has been shown to be effective in preventing spontaneous bacterial peritonitis (SBP) in liver cirrhosis . This therapy is associated with the appearance of quinolone-resistant Escherichia coli . However, only four cases of SBP caused by quinolone-resistant E . coli have been reported so far . We present four cases of quinolone-resistant E . coli SBP in three patients receiving oral quinolones, and who were on corticosteroid therapy to treat associated disorders.

Microbiology, 2002 Jan, 148(Pt 1), 79 - 86
Fast lysis of Escherichia coli filament cells requires differentiation of potential division sites; de Pedro MA et al.; Periodic activation of zonal peptidoglycan (murein) synthesis at division sites in Escherichia coli has been reported recently . Zonal synthesis is responsible for septum formation, whereas elongation of the cell sacculus is performed by diffuse insertion of precursors . Zonal synthesis can be triggered in ftsA, ftsQ and ftsI (pbpB) division mutants growing as filaments at the restrictive temperature, but not in ftsZ mutant strains . The lytic response to beta-lactams of cells able or unable to periodically trigger a zonal mode of murein synthesis could be substantially different . Therefore, we investigated the response to the bacteriolytic beta-lactam cefsulodin of ftsZ and ftsI mutants growing at the restrictive (42 degrees C) temperature . The ftsI cells lysed early and quickly after addition of the antibiotic . Sacculi of lysed cells were transversely cut in a very sharp way . In contrast the ftsZ strain lysed late and slowly after addition of the antibiotic and sacculi showed a generalized weakening of the murein network and extended breaks with a frayed appearance . No transversely cut sacculi comparable to those seen in the ftsI samples were found . Our results strongly support that beta-lactam-induced lysis occurs preferentially at division sites because of the activation of zonal murein synthesis at the initiation of septation.

Microbiology, 2002 Jan, 148(Pt 1), 51 - 9
The candicidin gene cluster from Streptomyces griseus IMRU 3570; Campelo AB et al.; A 205 kb DNA region from Streptomyces griseus IMRU 3570, including the candicidin biosynthetic gene cluster, was cloned and partially sequenced . Analysis of the sequenced DNA led to identification of genes encoding part of a modular polyketide synthase (PKS), genes for thioesterase, macrolactone ring modification, mycosamine biosynthesis and attachment to the macrolide ring, candicidin export and regulatory proteins . It represents the first extensive genetic characterization of an aromatic polyene macrolide antibiotic biosynthetic gene cluster . Of particular interest is the presence of the CanP1 loading domain (the first described as responsible for the activation of an aromatic starter unit) and the polypeptide CanP3 (carrying modules for the formation of five out of seven conjugated double bonds) . Disruption of the pabAB gene that encodes the starter unit of candicidin abolished its production {which was restored when exogenous p-aminobenzoic acid (PABA) was supplied to the culture} and resulted in an enhanced production of another antifungal compound that is barely detected in the wild-type.

J Agric Food Chem, 2002 Jan 16, 50(2), 279 - 83
Is the application of carbendazim harmful to healthy plants? Evidence of weak phytotoxicity in tobacco; Garcia PC et al.; To understand the phytotoxic effects that certain bezimidazole fungicides exert on plant growth, the aim of the present study was to determine the effect of the fungicide carbendazim, on foliar biomass, pigment content, and nutrient levels in tobacco plants (Nicotiana tabacum L . cv . Tennessee 86) . The fungicide applied was carbendazim with a purity of 100%, at three different rates: 1.3 mM (carb1), 2.6 mM (the recommended concentration, carb2), and 5.2 mM (carb3) . The control treatment was without carbendazim . The application of dosages of this fungicide lower than recommended (1.3 mM) resulted, on the one hand, in greater dry weight and, on the other, higher carotenoid concentrations, as well as higher N and K concentrations with respect to control . On the contrary, the application of the carbendazim dosage higher than recommended (5.2 mM) caused a decrease in dry weight and in all of the foliar pigments, as well as all of the nutrients, with respect to the other dosages and control . These results appear to indicate that besides its direct antibiotic action against pathogens, the effects of this fungicide in plants could be dangerous, especially at higher dosages . Nevertheless, the negative effects of carbendazim can be avoided by reducing the amount applied in current agriculture.

J Neurosurg, 2001 Aug, 95(2), 233 - 41
Diagnosis and management of pituitary abscess: a review of twenty-four cases; Vates GE et al.; OBJECT: Pituitary abscess is a rare but serious intrasellar infection . To better determine the salient signs and symptoms that help in making the diagnosis, and to determine the most appropriate treatment, the authors reviewed their experience in a series of 24 patients treated at the University of California at San Francisco . METHODS: Nine of the patients were female and 15 were male, and their mean age was 41.2 years (range 12-71 years) . Surprisingly, most patients in our series presented with complaints and physical findings consistent with a pituitary mass, but rarely with evidence of a serious infection . Headache, endocrine abnormalities, and visual changes were the most common clinical indicators; fever, peripheral leukocytosis, and meningismus were present in 33% or fewer of the patients . Imaging tests demonstrated a pituitary mass in all patients, but the features evident on computerized tomography and magnetic resonance studies did not distinguish pituitary abscesses from other, more common intrasellar lesions . Because of the ambiguous clinical features and imaging findings, most abscesses were not diagnosed before treatment; rather, the diagnosis was made during surgical exploration of the sella turcica, when the surgeon encountered a cystic mass containing pus . There were only two deaths in this series (8.3%) . Patients presenting with headache and visual changes noted improvement in almost all cases; patients with endocrine dysfunction generally did not recover normal pituitary function, but were easily treated with hormone replacement therapy . CONCLUSIONS: Antibiotic therapy is suggested for patients who have symptoms of sepsis, or for patients in whom specific organisms are identified from cultures obtained during surgery . The transsphenoidal approach is recommended over open craniotomy for surgical drainage.

J Ind Microbiol Biotechnol, 2001 Sep, 27(3), 177 - 82
The A-factor regulatory cascade and cAMP in the regulation of physiological and morphological development in Streptomyces griseus; Horinouchi S et al.; In the A-factor regulatory cascade leading to the onset of streptomycin biosynthesis and aerial mycelium formation in Streptomyces griseus, the A-factor receptor protein (ArpA) serves as a DNA-binding repressor and A-factor releases the repression by binding to ArpA and dissociating it from the DNA . Mutants defective in arpA therefore produce streptomycin and aerial hyphae in the absence of A-factor . A gene that inhibits streptomycin production and aerial hyphae formation in an arpA mutant was cloned on a high-copy-number plasmid and found to encode a eukaryotic-type adenylate cyclase (CyaA) . Consistent with this, an exogenous supply of cAMP at high concentration almost abolished streptomycin production and aerial hyphae formation . On the other hand, cAMP at lower concentrations stimulated or accelerated these developmental processes . The effects of cAMP were detectable only in arpA mutants, and not in the wild -type strain; an exogenous supply of cAMP or cyaA disruption in the wild-type strain caused almost no effect on these phenotypes . Thus the effects of cAMP became apparent only in the arpA-defective background . cAMP at high concentrations inhibited stringent response factor ppGpp production, which is important for the onset of antibiotic biosynthesis . cAMP also influenced the timing of tyrosine phosphorylation of more than nine proteins . These findings show that a cAMP regulatory relay for physiological and morphological development functions in a concerted and interdependent way with other signal transduction pathways.

Biochim Biophys Acta, 2002 Feb 1, 1558(2), 95 - 108
Interactions of the drug amphotericin B with phospholipid membranes containing or not ergosterol: new insight into the role of ergosterol; Milhaud J et al.; Amphotericin B (AmB) is an amphipathic polyene antibiotic which permeabilizes ergosterol-containing membranes, supposedly by formation of pores . In water, AmB forms chiral aggregates, modelled as stacks of planar dimers in which the joined polyene chains in each dimer turn round, from one dimer to the following in these stacks, by forming a helical array . Studies of the binding of AmB with L-dipalmitoylphosphatidylcholine (L-DPPC) and L-dilauroylphosphatidylcholine (L-DLPC) bilayers disclose the main following results . (1) An inversion of the helicity of the L-DPPC-bound AmB aggregates, when the L-DPPC bilayers are in the gel phase, is inferred from the evolution of the circular dichroism spectra of AmB+L-DPPC mixtures . (2) An AmB-induced gel-to-subgel transformation of L-DPPC bilayers, in the previous mixtures, is revealed by a differential scanning calorimetry study . (3) The role played by ergosterol in the location of phospholipid-bound AmB aggregates with respect to a phospholipid bilayer is directly demonstrated from atomic force microscopy observations of mica-supported AmB+L-DLPC mixtures, in the presence or absence of ergosterol . While in the absence of ergosterol AmB aggregates remained at the surface of the bilayer, in the presence of ergosterol they appeared embedded within this bilayer and became hollow-centered . As such an embedding in the hydrophobic core of a bilayer requires a rearrangement of the aggregates with respect to their architecture in water, this rearrangement is held responsible for the hollowing of aggregates . The hollow-centered sublayer-embedded AmB aggregates are thought to be the precursors of the formation of AmB pores.

Philos Trans R Soc Lond B Biol Sci, 2001 Dec 29, 356(1416), 1947 - 51
Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children; Belshe RB et al.; Studies in children and adults revealed cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV-T) to be well accepted, well tolerated and highly protective against culture-confirmed influenza, and to provide significant health benefits . A 2 year, multicentre, double-blind, placebo-controlled efficacy field trial of CAIV-T in children aged 15-71 months with annual re-immunization revealed the vaccine to be highly protective against culture-confirmed influenza . Vaccine induced serum and secretory antibodies in vaccinated children . Overall, during 2 years of study, vaccine was 92% protective against culture-confirmed influenza . During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97-like virus, a significantly drifted strain not well matched to the vaccine . Antibody studies on children given CAIV-T revealed that high titres of cross-reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95-like vaccine . Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients . In adults, vaccination with CAIV-T resulted in protection during experimental challenge with virulent wild-type viruses . An effectiveness trial in adults demonstrated significant benefits of CAIV-T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics) . General use of CAIV-T has the potential to significantly reduce the impact of influenza in children and adults.

J Gene Med, 2001 Nov-Dec, 3(6), 529 - 49
Dual-regulated expression technology: a new era in the adjustment of heterologous gene expression in mammalian cells; Moser S et al.; BACKGROUND: On the basis of the compatible streptogramin- and tetracycline-responsive expression systems, a series of dual-regulated expression systems have been established for use in sophisticated biopharmaceutical manufacturing, advanced gene therapy, and tissue engineering . METHODS: Dual-regulated expression concepts enable streptogramin- and tetracycline-responsive control of two different (sets of) transgenes (multi-regulated multigene metabolic engineering), dual-autoregulated expression configurations for one-step chromosomal integration of two antibiotic-adjustable expression units, and artificial regulatory cascades for multi-level regulation of transgenes and optimized integration of molecular interventions into mammalian regulatory networks . RESULTS: This report describes the construction and testing of a family of dual-regulated expression vectors which are compatible with the pTRIDENT vector construction kit, and, in some cases, adapted for retroviral expression technology enabling straightforward transduction of difficult-to-transfect cell lines such as primary cells and stem cells . CONCLUSIONS: Dual-regulated expression technology will probably become of prime interest for a variety of therapeutic applications, including biopharmaceutical manufacturing, gene therapy, and tissue engineering.

Zhonghua Jie He He Hu Xi Za Zhi, 2000 Apr, 23(4), 212 - 6
{Sequential non-invasive following short-term invasive mechanical ventilation in COPD induced hypercapnic respiratory failure}; Wang C et al.; OBJECTIVE: To estimate the feasibility and the efficacy of early extubation and sequential non-invasive mechanical ventilation(MV) in COPD with exacerbated hypercapnic respiratory failure . METHODS: 22 intubated COPD cases with severe hypercapnic respiratory failure due to pulmonary infection (pneumonia or purulent bronchitis) were involved in the study . At the time pulmonary infection had been significantly controlled (resolution of fever and decrease in purulent sputum, radiographic infiltrations, and leukocytosis . We call the time as "Pulmonary Infection Control Window", PIC window) after the antibiotic and the comprehensive therapy, the early extubation was conducted and followed by non-invasive MV via facial mask immediately in 11 cases (study group) . Other 11 COPD cases with similar clinical characteristics who continuously received invasive MV after PIC window were used as control group . RESULTS: The groups had similar clinical characteristics and gas exchange, initially and at the time of PIC window . For study group and control group, the duration of invasive MV was (7.1 +/- 2.9) vs (23.0 +/- 14.0) days, P < 0.01; the total duration of ventilatory support was (13 +/- 7) vs (23 +/- 14) days, P < 0.05; the incidence of VAP were 0/11 vs 6/11, P < 0.01; the duration of ICU stay was (13 +/- 7) vs (26 +/- 14) days, P < 0.05, respectively . CONCLUSIONS: In COPD patients requiring intubation and MV for pulmonary infection and hypercapnic respiratory failure, early extubation followed by non-invasive MV initiated at the point of PIC window may significantly decrease the invasive and total durations of ventilatory support, the risk of VAP, and the duration of ICU stay.

Endoscopy, 2002 Jan, 34(1), 43 - 53
Therapeutic biliary endoscopy; Shah SK et al.; An analysis of the recent medical literature on therapeutic biliary endoscopy shows that the new millennium has already brought several significant developments . However, although advances continue rapidly, several new questions have also arisen, paving the way for further research . Several studies during the last year have also focused attention on cost-effectiveness.

J Microbiol Methods, 2002 Mar, 49(1), 89 - 96
Cointegrate resolution following transposition of Tn1792 in Streptomyces avermitilis facilitates analysis of transposon-tagged genes; Pitman A et al.; The insertion sequence IS6100, belonging to the IS6 family, normally forms a cointegrate as an end product of transposition . The IS6100-based minitransposon, Tn1792, has been developed as a genetic tool to mutagenise antibiotic-producing Streptomyces . Here, we describe resolution of Tn1792 cointegrates in Streptomyces avermitilis that can facilitate both the initial isolation of Tn1792 insertion mutants and also the subsequent rescue of Tn1792-tagged sequences . This is the first reported example of cointegrate resolution for an IS6-type transposable element . As a result of mutagenesis, several putative genes involved in morphological development and antibiotic production have been isolated.

Zhonghua Zhong Liu Za Zhi, 1999 May, 21(3), 190 - 2
{Effect of cefodizime on cellular immunity in patients with lung cancer}; Ma Z et al.; OBJECTIVE: To study the enhancing effect of cefodizime on cellular immunity of patients with lung cancer . METHODS: The parameters of cellular immunity in blood and pulmonary alveoli were investigated in 45 patients with lung cancer complicated with lower respiratory tract infection (LRTI) and 10 non-cancer patients with LRTI . Nitroblue tetrazolium (NBT) reaction of polymorphonuclear neutrophils (PMN), the percentage of natural killer (NK) cells, and that of CD4+ cells, ratio of CD4+/CD8+ in peripheral blood, OD value of alveolar macrophages phagocyting neutral red, and IL-1 beta (ng/L) in broncho-alveolar lavage flind (BALF) were determined . RESULTS: The parameters examined in cancer patients with LRTI were significantly improved after cefodizime treatment, approaching to those seen in non-cancer patients with LRTI . The therapeutic results were better in patients treated with cifodizime than in patients treated with ceftriaxonum . CONCLUSION: Cefodizime is a better choice of antibiotic for the treatment of lung cancer complicated with lower respiratory tract infection . Its enhancing effect on systemic and local immune functions plays a role.

J Antibiot (Tokyo), 2001 Oct, 54(10), 789 - 96
Characterization of mutants defective in melanogenesis and a gene for tyrosinase of Streptomyces griseus; Endo K et al.; Nitrosoguanidine-induced melanin-negative mutants of Streptomyces griseus were classified according to their ability to produce streptomycin and A-factor, and to form aerial mycelium . A large proportion of the mutants showed deficiency in either antibiotic production and morphological development or both, suggesting close regulatory correlation between melanogenesis and morphological and physiological differentiation . The tyrosinase-encoding mel operon of S . griseus was cloned and examined for its role in melanogenesis of this organism . As in other Streptomyces homologues, the operon consisted of two open reading frames, melC1 encoding the putative cofactor and melC2 encoding the tyrosinase . Regardless of the distinct sequence similarity, introduction of the operon on plasmids failed to confer melanin production in the melanin-negative mutants, and the disruption of melC2 barely affected the melanin productivity, which indicated the presence of another enzyme involved in the melanogenesis in S . griseus . On the other hand, mel on a high-copy-number plasmid caused precocious aerial mycelium formation in Streptomyces lividans TK21 suggesting a stimulatory role of tyrosinase in morphological development.

Clin Infect Dis, 2002 Feb 1, 34(3), 318 - 23 Epub 2001 Dec 13.
Use of indicators to evaluate the quality of community-acquired pneumonia management; Nathwani D et al.; Quality-assessment indicators for community-acquired pneumonia (CAP) founded on health care structure, process, and outcome have been recommended as a potential audit tool to evaluate the delivery of care . We prospectively audited the treatment of 205 patients admitted with CAP to 2 hospitals in Dundee against some of these key standards . Patients with severe CAP were more likely to die (mortality rate, 42% versus 7%) and to receive antibiotics by the intravenous route (relative risk {RR}, 1.81; 95% confidence interval {CI}, 1.38-2.37) and within 4 hours of admission to the hospital (RR, 1.22; 95% CI, 0.92-1.62) . There was a lack of uniformity regarding the amount of oxygen prescribed, with evidence of poor case record and drug prescription chart documentation related to oxygen therapy . Adherence to the recommended antibiotic policy was associated with reduced risk of death or readmission to the hospital (RR, 0.58; 95% CI, 0.34-1.00) . However, in a multivariate analysis, severity of pneumonia was the strongest predictor of death or readmission (P=.004), and adherence to the antibiotic policy was not statistically significant (P=.154) . Our study has confirmed the value of quality indicators in evaluating our CAP management and has stimulated the development and implementation of a local hospital-based integrated care pathway.

Pediatrics . 2002 Jan;109(1):E15.
Venous air embolism during home infusion therapy; Laskey AL et al.; Venous air embolism (VAE) is a potential complication of surgical procedures as well as central venous access . There are several reports in the literature of VAE during the in-hospital use and placement of central venous access . However, we are unaware of previous cases of VAE in children who received home infusion therapy via central venous access . We report the occurrence of a VAE in a 2-year-old with a Broviac catheter for home intravenous antibiotic therapy . VAE occurred when a bolus of air was unintentionally administered as the mother removed the cassette from the pump when it was alarming air in line . The cassette and tubing had been placed into the pump without a fluid flush . After the tubing and cassette were removed from the pump, the air in the line was allowed to flow by gravity into the patient, resulting in the immediate onset of respiratory and neurologic symptoms . The mother administered 2 rescue breaths, and the child's color and breathing returned to normal over the next 2 minutes . After the child arrived in the emergency department, the child's mental status returned to normal and the remainder of her physical examination was unremarkable . She had an uneventful recovery and was discharged from the hospital the following day . Additional antibiotic administration was accomplished in the emergency department of a local hospital . VAE can occur spontaneously when there is an open venous structure 5 cm or more above the heart or if air is delivered under pressure into the venous system, such as during a laparoscopy or mishaps with infusion bags . The morbidity and mortality of VAE are related to the volume of air, rate of entrainment, the patient's underlying cardiorespiratory status, and the patient's position . Morbidity and mortality occur as a consequence of right ventricular outflow obstruction or end-organ dysfunction from left-sided obstruction of coronary or cerebral vasculature as air passes across a patent foramen ovale or through the pulmonary circulation . Of all the literature pertaining to VAE with central lines, there are no previous reports of VAE occurring during home infusion therapy in children . With managed care requiring shorter hospitalizations and more children being discharged from the hospital on home infusion therapy, parents and lay caregivers are being asked to administer medications and perform routine maintenance on central venous devices . In our case, despite the fact that the mother had been educated regarding the appropriate technique for medication administration, she forgot to purge the air from the line before connecting the tubing and administering the antibiotic . Although the infusion pump will alarm when there is air in the line, it detects air only in a small part of the line and this safety feature is not in play if the device is removed from the infusion pump and administered via gravity . If such safety precautions are not adhered to, then the volume of air that fills the intravenous tubing from the drip chamber to the patient (25-30 mL in the pediatric infusion pump tubing used in our patient) can be infused by gravity into the patient's venous system . Because the consequences of VAE are so severe, the focus should be on prevention . Pumps used for home infusion therapy should have appropriate alarms to alert caregivers to the presence of air in the line . Obviously, this will not totally prevent this complication as this type of pump was used in our patient . It is crucial to educate caregivers of patients with central venous access regarding the hazards of VAE and safety measures to prevent it . With the increased use of home infusion therapy, ongoing evaluations of complications related to this form of therapy are mandatory so that there is continued evaluation of practices and appropriate changes made when necessary to increase further the safety of these techniques.

Ophthalmology, 2002 Jan, 109(1), 13 - 24
Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update; Ciulla TA et al.; PURPOSE: To assess commonly used cataract surgery bacterial endophthalmitis prophylaxis techniques based on a systematic literature review and evidence rating . CLINICAL RELEVANCE: Prophylactic techniques to decrease the risk of bacterial endophthalmitis related to cataract surgery are commonly used, but the evidence justifying their use is unclear . LITERATURE REVIEWED: A MEDLINE search of the literature published in English or with English abstracts from 1966 to 2000 was performed using various combinations of relevant key words . Eighty-eight peer-reviewed papers were identified and judged worthy of review on the basis of predefined criteria . RESULTS: No prophylactic technique received the highest of three possible clinical recommendations (A, crucial to clinical outcome) . Preoperative povidone-iodine preparation received the intermediate clinical recommendation (B, moderately important to clinical outcome) . All other reported prophylactic interventions, including postoperative subconjunctival antibiotic injection, preoperative lash trimming, preoperative saline irrigation, preoperative topical antibiotics, antibiotic-containing irrigating solutions, and the use of intraoperative heparin, received the lowest clinical recommendation (C, possibly relevant but not definitely related to clinical outcome) based on weak and often conflicting evidence justifying their use . CONCLUSIONS: With regard to bacterial endophthalmitis prophylaxis in cataract surgery, current literature most strongly supports the use of preoperative povidone-iodine antisepsis.

Obstet Gynecol, 1997 Oct, 90(4 Pt 2), 689 - 91
Sacral osteomyelitis: an unusual complication of abdominal sacral colpopexy; Weidner AC et al.; BACKGROUND: Abdominal sacral colpopexy using permanent mesh is an established technique for repair of vaginal vault prolapse . Infection is not a frequent complication . We report two cases of lumbosacral osteomyelitis treated with intravenous antibiotics without mesh removal . CASES: The first patient had known advanced degenerative arthritis . Unremitting severe low back pain 5 years after abdominal sacral colpopexy prompted magnetic resonance imaging (MRI), revealing osteomyelitis and diskitis . The second patient developed symptoms 2 months postoperatively, and MRI indicated osteomyelitis with epidural abscess . Both patients received intravenous antibiotics, and neither required surgical debridement or mesh removal . CONCLUSION: Osteomyelitis can present remote from the operation and can be difficult to diagnose . Protracted parenteral antibiotic therapy can be definitive treatment without mesh removal.

Obstet Gynecol, 1997 Oct, 90(4 Pt 2), 674 - 6
Poor perinatal outcome associated with maternal Brucella abortus infection; Malone FD et al.; BACKGROUND: Reports suggest that perinatal infection with Brucella abortus does not cause poor obstetric outcomes, because of protective mechanisms in the human, not seen in animal species . CASE: We report a case of maternal brucellosis resulting in preterm labor, chorioamnionitis, placental abruption, and delivery of a live-born infant at 25 weeks' gestational age . Both maternal blood cultures and amniotic fluid cultures were positive for B abortus species, and delivery occurred despite aggressive antibiotic and tocolytic therapy . CONCLUSION: Maternal infection with B abortus during pregnancy can lead to significant perinatal morbidity, casting doubt on reports that human pregnancy is resistant to such infection.

Int J Clin Pract, 2001 Nov, 55(9), 627 - 31
Thalidomide: 40 years on; Diggle GE; Thalidomide was marketed in the late-1950s as a sedative and tranquilliser of exceptionally low general toxicity, but in 1961 it was implicated separately by Lenz and MacBride as the cause of the epidemic of congenital malformations that had been puzzling the world for some years . It is a very potent teratogen in humans, but in few other mammalian species; damage to the embryo is produced at specific stages of gestation, but the mechanism of embryopathic action is still not understood . Following the withdrawal of the drug worldwide, it was consigned to the history of medical tragedies . In 1965, however, Sheskin discovered that it was effective in treating erythema nodosum leprosum, a distressing complication of leprosy . As the drug is neither an antibiotic nor an analgesic, its action was assumed to be immunosuppressive . In Brazil the drug was used widely with few regulatory controls, since when more than 100 cases of congenital malformation have appeared . Sheskin's discovery led to the experimental use of thalidomide in many other indications thought to possess some immunological component . In some cases, e.g . Behcet's syndrome, graft-versus-host disease and aphthous ulceration in HIV-positive patients, the drug has been shown to possess some efficacy . And there is some evidence that it inhibits the replication of one of the immunodeficiency viruses . The AIDS community in the US has exerted much pressure on the FDA to allow the drug on to the market, although the use of a potent immunosuppressive drug of unknown mechanism in an immunodeficiency condition raises further questions . Thalidomide is not always beneficial; its use is associated with an increased mortality in epidermal necrolysis . In 1991, D'Amato confirmed it possessed antiangiogenic properties and this led to further trials in malignant conditions . Results were mixed, but those in multiple myeloma gave some grounds for optimism . In 1998, the FDA announced its extraordinary decision to grant marketing approval for thalidomide.

Acta Clin Belg, 2001 Sep-Oct, 56(5), 284 - 8
Implementation of pretravel advice: good for malaria, bad for diarrhoea; Peetermans WE et al.; Pretravel immunizations and health advice can substantially reduce the incidence of travel-related diseases . The aim of this study was to evaluate the implementation of pretravel advice among a homogenous group of students, who received similar written information on vaccination requirements and health advice . They were referred to the travel clinic (50%) or a general practitioner (50%) for vaccination, counselling and prescriptions . Eighty-four out of 110 students (76%) returned the questionnaire . Insect repellent was used by all and only 10 used the repellent for less than 75% of the time spent in malaria endemic areas . Malaria chemoprophylaxis was taken by all but one: chloroquine plus proquanil by 12 and mefloquine by 71 . Reported compliance with the dosing regimen was optimal in 64 students, 9 missed one dose and 10 stopped too early . Side effects due to antimalarials were reported by 25 (30%) . Diarrhoea during travel occurred in 43 students (51%) . Loperamide was used by 34 students with diarrhoea (79%), but only 2 out of 27 students with moderate to severe diarrhoea used the recommended self-treatment with a fluoroquinolone antibiotic . In conclusion, the recommendations of malaria prophylaxis were well implemented by most travellers despite a high incidence of self-reported side effects to antimalarials . The incidence of traveller's diarrhoea was high and the recommendation for early self-treatment of moderate to severe diarrhoea with a fluoroquinolone antibiotic in combination with loperamide was not put into practice.

Shock, 2001 Dec, 16(6), 419 - 24
Increased neutrophil motility by beta-glucan in the absence of chemoattractant; Harler MB et al.; Systemic candidasis is a life-threatening complication of antibiotic and immunosuppressive therapies and can alter host defense mechanisms through pathways that are poorly understood . Promotion of polymorphonuclear leukocyte (PMN) chemotaxis by beta-glucan towards fMLP or IL-8 gradients demonstrates a fundamental effect on host defenses by pathogenic fungi . The aim of the present study was to determine whether recognition of beta-glucan is sufficient to alter PMN motility in the absence of agonists of G-coupled protein chemotactic receptors . Present findings demonstrate a profound increase in PMN motility by beta-glucan supplementation of a fibronectin substratum in an underagarose migration assay . Motility on beta-glucan included a 3-fold increase in distance of migration, as well as a 5-fold increase in the number of PMNs recruited into the motile phase as compared to motility on fibronectin alone . This promotion of motility is determined by the beta2 integrin complement receptor 3 (CR3) (CD11b/CD18) rather than the beta1 integrin very late antigen 3 (VLA-3), which mediates chemotaxis on beta-glucan-supplemented matrix towards fMLP . PMN motility on beta-glucan-supplemented fibronectin was selectively decreased by inhibitors of pp60 src and ras, whereas motility was promoted by inhibition of p38-MAPK . No effect of these inhibitors was seen on PMNs migrating on fibronectin alone . Migration on beta-glucan-supplemented fibronectin, but not on fibronectin alone, was negatively regulated by protein kinase C (PKC) or cAMP activation . These findings indicate that beta-glucan is sufficient to alter the migratory capacity of PMN in the absence of costimulation by fMLP . Enhanced PMN migration on beta-glucan is mediated through specific integrins and second messenger pathways that are distinct from those utilized by PMNs migrating in the absence of beta-glucan.

Vet Radiol Ultrasound, 2001 Nov-Dec, 42(6), 496 - 503
Radiographic findings during recovery from discospondylitis; Shamir MH et al.; The diagnosis of discospondylitis is based on radiographic changes in the vertebrae . The limitations of this method are the time gap between the onset of clinical signs and the first appearance of the radiographic findings, as well as the disassociation between the clinical and radiographic signs during recovery . It is known that the radiographic changes appear only two to four weeks after the onset of clinical signs, but the characteristics of radiographic changes during recovery has yet to be documented, thus making follow-up radiographs difficult to interpret . A prospective and retrospective study was designed to document typical radiographic changes during recovery from discospondylitis . We reviewed 12 dogs that had complete and uneventful recovery with antibiotic therapy alone . Periodic follow-up radiographs and clinical examinations were conducted up to five months after the onset of clinical signs to correlate between the clinical status and radiographic changes during recovery . Although the clinical signs improved within the first 10 days of antibiotic therapy, the radiographic deterioration continued before regression and signs of radiographic recovery were noticed . This radiographic deterioration, despite successful antibiotic therapy, appeared shorter in young dogs (less than one year old) and lasted three to nine weeks in older dogs.

Int J Circumpolar Health, 2001 Nov, 60(4), 632 - 9
Longitudinal observations (1987-1997) on the prevalence of middle ear disease and associated risk factors among Inuit children of Inukjuak, Nunavik, Quebec, Canada; Bruneau S et al.; The prevalence of middle ear disease in 2-6 year old children in 1997 was compared with that observed in 1987 in the same Inuit community in northern Quebec . Risk and protective factors associated with middle ear disease were also assessed . A total of 122 children participated . The assessments included: otological examination, cerumen sampling for analysis of organochlorine compounds, medical file review, and parent questionnaire regarding environmental and lifestyle factors . Comparison of ear examination results in 1997 and 1987 showed that there had been no change in the prevalence of chronic otitis media {9.4% to 10.8%} and proportion of ear drums with minimal scarring {45.6% to 45.4%}, an increase in the proportion of normal ear drums {23.9% to 39.0%}, a decrease the proportion with maximal scarring {17.8% to 2.0%} and little difference in the rate of serous otitis media {3.3% to 2.8%} . Factors found to be significantly associated with middle ear disease included: number of persons/bedroom, number of siblings with a history of ear disease, age at first, second and third visit to the nursing station for ear problems, and type of milk (formula vs . non-formula) in bottle fed children.

West Afr J Med, 2001 Apr-Jun, 20(2), 146 - 51
Benign breast disease at Wesley Guild Hospital, Ilesha, Nigeria; Adesunkanmi AR et al.; A prospective survey of 225 patients carried out over a period of 7years (1992 - 1999) to determine the pattern and outcome of benign breast diseases . Two hundred and seventeen (96.4%) were females and 8 males, with the age ranging from 14-63 years, mean 28.7 SD+10.6 years . The mean age for patients with fibroadenoma was 24 years and 31.6 years for fibrocystic disease of the breast . One hundred and ninety six patients (87.2%) presented with breast lumps or mass, non-menstrual cycle and menstrual cycle related pain in 39(17.3%) and 32(13%) patients respectively and nipple discharge in 60 patients (26.7%) . Mean duration of symptoms was 0.91+0.64 years, 2 + 1.2 weeks for inflammatory lesions and 0.86 + 0.56 yers for benign tumours and also menstrual cycle related breast pain . Right side was involved in 162 patients (72%), 85(38%) left side and 77(34.2%) bilateral . Clinical diagnosis was fibrocystic disease 96(42.7%) . Fibroadenoma 89 (39.5%), inflammatory conditions 35(15.7%), galactocele in 9(40%) and gynaecomastia in 7(3%) of the patients . Excisional or incisional biopsy was carried out in 197 patients (87.5%), antibiotic and analgestic administration in 35(15.6%) and 29(13%), respectively . Histopathologic analysis showed fibroadenoma in 91 (46.2%), fibrocystic disease 83 (42.2%), and others in 23 (11.6%) cases . The mean follow-up period was 10 months for tumours and I month for others . Postoperative complications were infrequent, there were recurrence either on the ipsilateral or contralateral breast in 10(4.4%) patients of which 3(1.3%) cases were malignant . CONCLUSION: Fibroadenoma was the most common benign breast disease, followed by fibrocystic disease of the breast . Postoperative complications were uncommon.

Ugeskr Laeger, 2001 Dec 3, 163(49), 6904 - 7
{Treatment of tibial shaft fractures in Denmark}; Kunov A et al.; INTRODUCTION: Only a few randomised studies have been published on the treatment of tibial shaft fractures . We therefore expected a great diversity in the choice of treatment methods in Denmark . In order to analyse this, we carried out a questionnaire investigation . MATERIAL AND METHODS: In autumn 1997, a questionnaire was sent to all departments in Denmark where tibial fractures are treated . The fractures were classified according to stability, amount of energy, and the degree of soft tissue injury . RESULTS: Ninety-three per cent of the departments answered the questionnaire . We present here the results with respect to the use of antibiotics, thrombosis prophylaxis, invasive pressure measuring, and the choice of treatment: conservative or operative methods and techniques . DISCUSSION: As expected, we found a significant variation in the choice of treatment of tibial shaft fractures in Denmark . This is consistent with the recommendations in the literature, which vary somewhat and are mostly based on non-randomised studies.

Yakugaku Zasshi, 2001 Dec, 121(12), 995 - 1004
The participation of pharmacists in a team to introduce a clinical pathway to laparoscopic cystectomy in obstetrics and gynecology; Sekine Y et al.; In the Department of Obstetrics and Gynecology at our hospital, a team of doctors, pharmacists, nurses, and other medical staff was established to prepare a clinical pathway for laparoscopic cystectomy . Various data on clinical charts including the use of drugs were collected from 57 patients by pharmacists and nurses . Based on the analysis of these data, hospitalization period, method of preoperative bowel preparation, time to initiation of food intake, duration of antibiotic administration, and time and content of pharmaceutical instructions to patients of dosage and administration were determined . Criteria for variances requiring the doctor's directions were determined for fever, wound pain, and vomiting . The clinical pathway established here allows of not only the efficient and uniform care of patients, but also the active exchange of opinions among members of the medical team . Moreover, most patients who replied to a questionnaire said that they were at ease during hospitalization because they had received detailed information about the clinical pathway including the use of drugs before surgery . Thus, the participation of pharmacists on a medical team that is introducing a clinical pathway is particularly important because the use of drugs and pharmaceutical care are an important part of good patient care.

Nippon Rinsho, 2001 Dec, 59(12), 2410 - 5
{Management of complications in patients with chronic myelogenous leukemia}; Yoshida M; Management of complications in patients with chronic myelogenous leukemia(CML) were reviewed . In chronic phase, the complications due to the increased WBC are not common . Currently, most patients are treated with interferon and/or hydroxyurea . Although the clinical benefit of interferon therapy has been proven with randomized trials, side effects with interferon are significantly higher than hydroxyurea . Common side effects are fatigue, weight loss, insomnia, depression and neurotoxicity . The complications following stem cell transplantation are classified into three categories: 1) regimen related toxicities of heart, lung and liver, 2) acute complications related to hematoimmune disturbance including acute and chronic graft-versus-host disease and infectious complications, 3) long term consequences of stem cell transplantation . During blastic phase, management of infectious complications is important.

Otolaryngol Pol, 2001, 55(4), 417 - 20
{Latent otogenic cerebellar abscess.}; Szmeja Z et al.; A case of latent otogenic cerebellar abscess is presented during chronic otitis media with cholesteatoma, in 42-year-old woman . Good results of the treatment were obtained by draining and substituting the content of abscess into antibiotic solution.

Dent Traumatol, 2001 Dec, 17(6), 254 - 9
Periodontal response to two intracanal medicaments in replanted monkey incisors; Thong YL et al.; Intracanal medicaments are recommended for use in replanted teeth to inhibit inflammatory root resorption . This study compared the effect of calcium hydroxide (Pulpdent) and a corticosteroid-antibiotic paste (Ledermix) on periodontal healing and root resorption following replantation . Incisors of eight Macaca fascicularis monkeys were extracted, stored dry for 15 min and replanted . After 11 days, root canals in two adjacent maxillary incisors were treated with one medicament and contralateral incisors with the other medicament, or left as untreated controls . Animals were sacrificed 8 weeks later and the teeth prepared for histomorphometric evaluation of periodontal ligament inflammation and root resorption . Periodontal ligament inflammation and inflammatory root resorption were markedly inhibited by both calcium hydroxide and corticosteroid-antibiotic relative to untreated controls . Replacement resorption was lowest in the corticosteroid-antibiotic group, and significantly (P<0.05) more normal periodontal ligament was present in this group (79.6%) than in calcium hydroxide and control groups (64.6% and 62.7%, respectively) . Treatment with the corticosteroid-antibiotic inhibited inflammatory resorption and was slightly more effective than calcium hydroxide in producing a periodontal healing response.

J Neurosurg, 2001 Dec, 95(6), 1083 - 96
The history and evolution of transsphenoidal surgery; Liu JK et al.; Initial attempts at transcranial approaches to the pituitary gland in the late 1800s and early 1900s resulted in a mortality rate that was generally considered prohibitive . Schloffer suggested the use of a transsphenoidal route as a safer, alternative approach to the sella turcica . He reported the first successful removal of a pituitary tumor via the transsphenoidal approach in 1906 . His procedure underwent a number of modifications by interested surgeons, the culmination of which was A . E . Halstead's description in 1910 of a sublabial gingival incision for the initial stage of exposure . From 1910 to 1925, Cushing, combining a number of suggestions made by previous authors, refined the transsphenoidal approach and used it to operate on 231 pituitary tumors, with a mortality rate of 5.6% . As he developed increasing expertise with transcranial surgery, however, Cushing reduced his mortality rate to 4.5% . With the transcranial approach, he was able to verify suprasellar tumors and achieve better decompression of the optic apparatus, resulting in better recovery of vision and a lower recurrence rate . As a result he and most other neurosurgeons at the time abandoned the transnasal in favor of the transcranial approaches . Norman Dott, a visiting scholar who studied with Cushing in 1923, returned to Edinburgh, Scotland, and continued to use the transsphenoidal procedure while others pursued transcranial approaches . Dott introduced the procedure to Gerard Guiot, who published excellent results with the transsphenoidal approach and revived the interest of many physicians throughout Europe in the early 1960s . Jules Hardy, who used intraoperative fluoroscopy while learning the transsphenoidal approach from Guiot, then introduced the operating microscope to further refine the procedure; he thereby significantly improved its efficacy and decreased surgical morbidity . With the development of antibiotic drugs and modern microinstrumentation, the transsphenoidal approach became the preferred route for the removal of lesions that were confined to the sella turcica . The evolution of the transsphenoidal approaches and their current applications and modifications are discussed.

Recenti Prog Med, 2001 Nov, 92(11), 663 - 6
{Popliteal (Baker's) cyst in a patient with tubercular arthritis . Report of a case and review of the literature}; Bianco G et al.; The Baker's cyst is a distension of the bursa subtendinea and is caused by noninfectious knee effusion secondary to arthrosis, meniscal tears, trauma, rheumatoid arthritis, gout, or any other form of sinovitis, like rheumatoid arthritis . An infected popliteal cyst is much less common; tuberculous arthritis is exceptional, in fact only four cases are described in literature . Herein we describe an additional tbc case of a 51 years old men, who has been initially treated with cytostatic and corticosteroid agents, for a suspected rheumatoid arthritis . The review of the literature suggests the importance of a correct approach to the diagnosis, based on the analysis and culture of the synovial fluid, because delays latency of effective antibiotic therapy can result in permanent joint damage that invalidate the patients.

Vestn Oftalmol, 2001 Sep-Oct, 117(5), 51 - 2
{Treatment of chlamydial conjunctivitis}; Aznabaev MT et al.; A new method for treating chlamydial conjunctivitis consists in injections of ciprofloxacine for intravenous injections, which is injected (1 ml) under the inferior vault of the conjunctiva on novocaine pad (0.5 ml 0.5% solution) and intravenously by drip infusion (99 ml) twice daily for 7-10 days . The treatment led to clinical cure in all patients, no relapses were observed . This method ensures a high therapeutic effect and accelerates the recovery of patients with chlamydial conjunctivitis by 4.6 days . The method is recommended for patients with complicated forms of chlamydial conjunctivitis in severe and protracted cases with concomitant urogenital chlamydial infection and concomitant chronic gastrointestinal diseases, when oral antibiotic therapy is undesirable or precluded.

Otolaryngol Pol, 2001, 55(3), 323 - 6
{The case of Wegener's granulomatosis of the nose, larynx and ear}; Wojciechowski I et al.; We have described a rare case of Wegener's granulomatosis in our 41-year old patient, located in the nose, larynx and ear . The disease usually presents as a triad of respiratory, vascular and kidney location . It may occur as a rapid or indolent progress . We have shown in our paper diagnostic difficulties connected with this disease . The biopsies of involved organs and blood tests are the best steps of establish proper diagnosis . Antineutrophil cytoplasmic antibodies (ANCA) are typical markers of Wegeners's granulomatosis . The conservative therapy including immunosuppression and surgical treatment (laserotherapy) are main methods of management . Our patient was given antibiotic therapy, and immunosuppressive therapy . Her condition improved during the first hospitalisation . Remission lasted very short, and she was admitted to the hospital again and underwent intensive investigations and therapy . We observed dyspnea caused by subglottic stenosis . The histologic examination of the tracheal mucosa showed granulomatous inflammation . After intensive therapy our patient felt better . She has been in our records till now, we observe no progress of disease . Finally, we would like to pay attention to the fact, that early diagnosis is important to prevent complications such subglottic stenosis which can lead to death.

Otolaryngol Pol, 2001, 55(3), 293 - 8
{Intracranial complications of sinusitis in the material of the Otolaryngology Department, K . Marcinkowski University of Medical Sciences in Poznań in the years 1964-1999}; Szmeja Z et al.; In the period of 35 years 25 patients with intracranial complications of paranasal sinusitis were treated in the Department of Otolaryngology of the Karol Marcinkowski University School of Medical Sciences in Poznan . In the past 15 years the number of complications decreased annually by half . Intracranial sinusal complications were more frequently present in young men . In 25 patients abscesses of the frontal lobe and epidural abscesses were most often diagnosed . Surgical treatment was carried out in each case when the inflammation process spread into the bony parts or into intracranial space . The method of choice in treatment of frontal lobe abscess and subdural abscesses is elimination of sinuses inflammatory foci with a simultaneous evacuation of the abscess by puncturing of the abscess and gradual exchange of its content into antibiotic solution . Intensive antibiotic therapy was carried out for the period of 4 weeks . Mortality rate in our material concerned patients with the brain frontal lobe abscesses and amounted to 12% . In the last 15 years we succeeded to treat all 17 patients.

Ann Ital Chir, 2001 May-Jun, 72(3), 317 - 21
{Bacterial endocarditis . Unusual complications of acute diverticulitis}; Mastrandrea G et al.; BACKGROUND: Colon diverticular disease represents an affection with high prevalence in the western countries . It appears particularly insidious in the elderly population for the presence of concomitant illnesses . CLINICAL CASE: A patient (> 80 years old) is submitted to surgical intervention in emergency sec . Hartman for acute diverticulitis and pelvic abscess . The post-operating time has been complicated for the arising of a fever resistant to the common antibiotic therapy, in absence of abdominal and respiratory objectivity . An accurate clinical examination has set the suspect of bacterial endocarditis, confirmed to the echocardiographic examination . DISCUSSION: The acute complicated diverticulitis therapy variates in according to the clinical presentation, the complications and the experience of the different Authors . A first conservative approach foresees the Total Parenteral Nutrition (TPN) and the wide spectrum antibiotic therapy and the eventual percutaneous drainage . The surgical treatment, realized with "open" or laparoscopic method, foresees the resection of the sick intestinal tract and the packing of a temporary preternatural anus . However, some Authors prefer an intestinal anastomosis performed in single time with the resection . Among all the complications, the most frequent are those affecting the respiratory and cardiovascular apparatus, as well as the sepsis . The bacterial endocarditis is not signalled in most recent international Literature . CONCLUSION: The bacterial endocarditis must be suspected in case of common antibiotic therapy resistant fever, with negative abdominal and pulmonary objectivity, arising after a septic surgical intervention.

Curr Opin Pharmacol, 2001 Oct, 1(5), 482 - 90
Therapeutic options for the management of influenza; Ison MG et al.; Over the past few years a novel class of antiviral agents, the neuraminidase inhibitors, has been found to be safe and effective in the prevention and treatment of influenza . Previously available agents, the M2 inhibitors amantadine and rimantadine, could only be used to treat influenza A infections and resistance develops rapidly . Zanamivir (Relenza) and oseltamivir (Tamiflu), the two clinically available neuraminidase inhibitors, are effective for treating both influenza A and B infections in adults and children and have also been shown to reduce the frequency of antibiotic-requiring complications of influenza infections . Inhaled zanamivir has shown benefit in treating acute influenza with mild to moderate underlying asthma or chronic obstructive pulmonary disease . Studies are needed to examine the use of these agents, alone or in combination with M2 inhibitors or ribavirin, in the management of severe infections in hospitalized patients and immunocompromised hosts . Studies are also needed to address other groups at increased risk for influenza complications, such as pregnant women and children below one year of age.

Genetika, 2001 Oct, 37(10), 1340 - 7
{Interspecies conjugation of Escherichia coli-Streptomyces globisporus 1912 using integrative plasmid pSET152 and its derivatives}; Luzhetskii AN et al.; Streptomyces globisporus 1912 produces a novel angucycline antitumor antibiotic landomycin E (LE) . To study the LE biosynthetic gene cluster in detail, a system for the conjugal transfer of the integrative plasmid pSET152 from Escherichia coli into S . globisporus 1912 has been developed . It was shown that this plasmid integrates into two sites of the S . globisporus chromosome and is stably inherited under nonselective conditions . pSET152+ exconjugants of the strain 1912 are characterized by a significant decrease in LE synthesis (by 50-90%) . A negative effect of pSET152 integration on antibiotic production was observed even upon the use of the recipient strain with increased LE synthesis, although in this case, the level of LE production in ex-conjugants was 120-150% of that in the original strain 1912 . Based on pSET152, a vector system for gene knockouts in S . globisporus was developed . The effectivity of this system was shown in the example of disruption of the lndA gene encoding the key enzyme of LE synthesis (beta-ketoacylsynthase) . Inactivation of this gene was shown to lead to the cessation of LE biosynthesis.

Cancer Chemother Pharmacol, 2001 Nov, 48(5), 347 - 55
Phase I clinical trial of 7-cyanoquinocarcinol (DX-52-1) in adult patients with refractory solid malignancies; Bunnell CA et al.; PURPOSE: A phase I study of the antitumor antibiotic 7-cyanoquinocarcinol, DX-52-1, was conducted in patients with refractory solid malignancies . This study sought to determine the maximum tolerated dose and principal toxicities of this agent and to characterize its pharmacokinetic behavior . METHODS: Patients were required to have adequate bone marrow, renal and hepatic function . DX-52-1 was administered by i.v . continuous infusion over a 6-h period each week for four consecutive weeks followed by a 2-week rest period, which constituted one cycle of treatment . RESULTS: Initial dose levels were 3, 6, and 10 mg/m2 . An intermediate dose level of 8 mg/m2 was added after acceptable toxicity was observed at the 6 mg/m2 dose level, but dose-limiting toxicities, including life-threatening ones, were seen at the 10 mg/m2 dose level in all three patients . The maximum tolerated dose (MTD) was subsequently determined to be 6 mg/m2 . Because a clear pattern of toxicities was not initially evident, a larger than usual number of additional patients (16) were enrolled at the MTD to better distinguish toxicities due to the study drug from those secondary to the patients' underlying malignancies . Even at the MTD, the drug was poorly tolerated, with gastrointestinal toxicities (abdominal pain, nausea, vomiting and increased liver function tests) predominating and dose-limiting . Pharmacokinetic studies revealed that the mean maximum plasma concentration of DX-52-1 in patients evaluated at the MTD (138.8 +/- 59.3 ng/ml, n = 19) was considerably lower than the concentrations required for cytostatic or cytotoxic activity against sensitive human tumor cell lines in vitro . Further, the weekly dose intensity of the most efficacious treatment schedule identified during in vivo antitumor efficacy studies was 60 times greater than the 6 mg/m2 weekly dose tolerated by cancer patients . None of the 33 patients participating in this study, including the 22 patients evaluated at the MTD, had any response to treatment . CONCLUSION: Given the poor tolerability, the inability to achieve drug levels necessary to inhibit in vitro or in vivo tumor growth, and the lack of any responses in our study, DX-52-1, as given by this schedule, does not appear to warrant further investigation in phase II studies.

Hernia, 2001 Sep, 5(3), 124 - 8
Repair of giant hernias using more prosthesis; Trivellini G et al.; Giant incisional hernias with total loss of substance are an ominous pathological condition characterized by massive depletion of muscular and fascial tissue, by complete loss of the anatomical and physiological function of the abdominal wall and by severe respiratory and visceral involvement . Over a 10-year period we operated 270 patients with voluminous incisional hernias, 12 of which had a total loss of substance . There was no intraoperative mortality . One patient died of myocardial infarction on the fifth and one died of intestinal occlusion and peritonitis the 11th postoperative day . Early postoperative complications occurred in only one patient who had skin necrosis with an infection at the polypropylene mesh . This was successfully treated with systemic antibiotic therapy and topical medication of the wound . There was also one minor recurrence over the pubis 1 year after the operation that required a new operation to replace the mesh . No respiratory complications occurred and all patients were normally active . The good results reported in our series encourage us to continue in this direction even though these patients are at high risk.

Pharm Res, 2001 Nov, 18(11), 1556 - 61
Liquid dose pulmonary instillation of gentamicin PulmoSpheres formulations: tissue distribution and pharmacokinetics in rabbits; Smith DJ et al.; PURPOSE: To assess the pharmacokinetics and biodistribution of gentamicin, delivered as PulmoSpheres formulations in rabbit serum and lung tissue following intratracheal instillation in a perflubron vehicle . METHODS: Rabbits were anesthetized, intubated, and mechanically ventilated with O2 (FiO2 = 0.50) . Animals were then given 5 mg/kg gentamicin either intravenously, intramuscularly (TM), or intratracheally (IT) gentamicin PulmoSpheres formulation, instilled in 1.8 ml/kg of liquid perflubron vehicle . Serum and lung lobe sections were collected at multiple time points and assayed for gentamicin content . RESULTS: Serum gentamicin levels peaked at 64.7 microg/ml, 11.2 microg/ml, and 5.0 microg/ml following intravenous, TM, and IT administration, respectively . Absolute bioavailabilitv at 8 h for IM administration was 76.8% and 57.0% when delivered IT . Although peak lung levels of drug were reached within 1 h, total lung gentamicin concentration after IT administration was more than two orders of magnitude greater than that achieved following TM administration (680,540 vs . 4,985 microg min, respectively) with significant levels of the antibiotic remaining in the lung even after 1 week . CONCLUSIONS: High levels of gentamicin in lung tissue can be achieved by instillation of a gentamicin PulmoSpheres formulation in a perflubron vehicle, termed liquid dose installation, without reaching toxic systemic levels allowing for increased local delivery of agents such as gentamicin at the site of the infection.

J Infect Dis, 2002 Jan 1, 185(1), 20 - 7 Epub 2001 Dec 14.
High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy; Limaye AP et al.; Preemptive antiviral therapy in transplant patients is thought to be less likely to lead to antiviral resistance than is routine prophylaxis . Cytomegalovirus (CMV)-seropositive lung transplant patients (R+) were assigned to receive pp65 antigen-guided ganciclovir therapy, and seronegative recipients of organs from seropositive donors (D+/R-) were assigned to receive initially preemptive and then routine ganciclovir prophylaxis . The incidence of infection with ganciclovir-resistant (ganR) CMV was assessed retrospectively . GanR CMV infection developed in 4 (9%) of 45 patients, at a median of 4.4 months (range, 3.1-6.6 months) after transplantation, and was more common among D+/R- patients than among R+ patients (3 of 11 vs . 1 of 34; P =.04) . The incidence among patients who received preemptive therapy was similar to that among patients who received routine prophylaxis . All ganR isolates contained a UL97 mutation . GanR CMV infection occurs in nearly 10% of lung transplant recipients, despite preemptive antiviral therapy, and is more common among D+/R- patients.

J Pharm Biomed Anal, 2002 Jan 15, 27(3-4), 409 - 19
Comparison of three chiral stationary phases with respect to their enantio- and diastereoselectivity for cyclic beta-substituted alpha-amino acids; Schlauch M et al.; Three chiral stationary phases were examined for the enantio- and diastereoseparation of cycloaliphatic beta-substituted alpha-quaternary alpha-amino acids . Resolution of diastereomeric analytes is feasible with a chiral crown ether based column, whereas the separation of enantiomers, except for one pair of amino acids, could not be achieved . The two chiral stationary phases with the glycopeptide antibiotic teicoplanin and with the copper(II)-D-penicillamine complex, respectively, are, however, both very potent in the separation of the enantiomeric, as well as of the diastereomeric amino acids . A baseline separation of all four stereoisomeric forms in one chromatographic run was possible with the exception of one type of amino acid . The results of the method development are presented in this paper.

Teratog Carcinog Mutagen, 2002, 22(1), 51 - 8
No significant increase in chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with spiramycin; Rencuzogullari E et al.; In this study, the chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were investigated in human lymphocytes treated with spiramycin antibiotic (trade name, rovamycin) . Spiramycin did not induce the CAs and SCEs, and also did not decrease the mitotic index (MI) . However, spiramycin decreased the replication index (RI) only at 48 h treatment times .

Antimicrob Agents Chemother, 2002 Jan, 46(1), 245 - 7
In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp; Arikan S et al.; We investigated the in vitro interaction of caspofungin and amphotericin B for clinical isolates of Aspergillus and FUSARIUM: Synergy tests were performed using the checkerboard method and following the NCCLS M38-P guidelines in Antibiotic Medium 3 broth supplemented to 2% glucose . Antagonism was not observed for any of the isolates tested . Caspofungin and amphotericin B were synergistic or synergistic to additive for at least half of the isolates.

Toxicol Lett, 2002 Jan 25, 126(2), 131 - 41
Toxicological studies of doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma; Gelperina SE et al.; Polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (NP) were shown to enable the transport of a number of drugs including the anti-tumour antibiotic doxorubicin (DOX) across the blood-brain barrier (BBB) to the brain after intravenous administration and to considerably reduce the growth of brain tumours in rats . The objective of the present study was to evaluate the acute toxicity of DOX associated with polysorbate 80-coated NP in healthy rats and to establish a therapeutic dose range for this formulation in rats with intracranially implanted 101/8 glioblastoma . Single intravenous administration of empty poly(butyl cyanoacrylate) NP in the dose range 100-400 mg/kg did not cause mortality within the period of observation . NP also did not affect body weight or weight of internal organs . Association of DOX with poly(butyl cyanoacrylate) NP did not produce significant changes of quantitative parameters of acute toxicity of the anti-tumour agent . Likewise, the presence of polysorbate 80 in the formulations was not associated with changes in toxicity compared with free or nanoparticulate drug . Dose regimen of 3x1.5 mg/kg on days 2, 5, 8 after tumour implantation did not cause drug-induced mortality . The results in tumour-bearing rats were similar to those in healthy rats . These results demonstrate that the toxicity of DOX bound to NP was similar or even lower than that of free DOX.

Eur J Obstet Gynecol Reprod Biol, 2002 Jan 10, 100(2), 181 - 4
Laminaria dilatation and evacuation for pregnancies with mid-trimester premature rupture of membranes: a retrospective cohort study; Halperin R et al.; OBJECTIVE: To assess the efficacy and risk of chorioamnionitis with laminaria tents and uterine evacuation in patients with mid-trimester premature rupture of membrane (MPROM) . STUDY DESIGN: A retrospective cohort study of 34 women, admitted between January 1995 and May 1999 with confirmed mid-trimester (14-23 weeks) PROM and 34 controls matched for gestational age, undergoing elective termination . All women underwent cervical dilatation by the use of laminaria tents followed by uterine evacuation (D approximately equals E) . Perioperative complications were retrieved from the medical records and long-term ones by telephone questionnaire . RESULTS: Apart from one case requiring a change in antibiotic, no short- or long-term complications were reported . Although, in 8 out of 19 study cases (42%) endocervix culture was positive . The number of laminaria tents used was similar in both groups . The future pregnancy rate was higher in the study group but included four early spontaneous abortions and one ectopic pregnancy . CONCLUSION: Evacuation of uterus following cervical dilatation by laminaria tents in patients presenting with MPROM is safe, and probably not associated with future adverse pregnancy outcome.

Surg Neurol, 2001 Nov, 56(5), 338 - 43
Ocular manifestations of sphenoid mucoceles: clinical features and neurosurgical management of three cases and review of the literature; Hejazi N et al.; BACKGROUND: Sphenoid mucoceles (SMCs) are unusual lesions, with about 130 cases reported in the literature . Although benign, they may involve the orbit and cause acute restrictive ophthalmoplegia, proptosis, and reduced visual acuity . METHODS AND RESULTS: We present three cases (1 male, 2 females, aged 35, 36, and 46 years) of orbital involvement with acute decreased visual acuity by SMC . The lesions were promptly excised via a transnasal approach to decompress the optic nerve . After the decompression, the patients recovered completely . CONCLUSION: We believe that immediate surgical drainage of the SMC and prolonged antibiotic therapy are necessary and resulted in recovery of visual acuity . Prompt microsurgical transsphenoidal decompression is simple, effective, safe, and is necessary for avoiding persistent visual loss . Antibiotic therapy alone usually results in a poor outcome . We discuss the etiology, clinical manifestations, and management of this rare condition in the light of 130 other cases in the literature.

Biomacromolecules, 2001 Spring, 2(1), 95 - 104
Biotransformations catalyzed by multimeric enzymes: stabilization of tetrameric ampicillin acylase permits the optimization of ampicillin synthesis under dissociation conditions; Fernandez-Lafuente R et al.; The importance of the stabilization of the quaternary structure of multimeric enzymes has been illustrated using a model reaction with great industrial relevance: the enzymatic synthesis of ampicillin from 6-amino penicillanic acid (6APA) and phenylglycine methyl ester (PGM) catalyzed by the tetrameric enzyme alpha-amino acid ester hydrolase from Acetobacter turbidans . The stabilization of the multimeric structure of the enzyme was achieved by multi-subunit immobilization of the enzyme followed by its further solid-phase chemical intersubunit cross-linking with polyfunctional macromolecules (dextran-aldehyde) . This stabilized derivative has permitted the study of the reaction under conditions where nonstabilized enzyme molecules tended to dissociate (e.g., absence of phosphate ions) . Synthetic yields improved from around 65%, under conditions where the nonstabilized derivative was stable, to around 85% in conditions where only the stabilized derivative could be utilized (40% methanol and absence of phosphate ions) . When using high concentrations of PGM, a significant worsening of the reaction performance was detected with a significant decrease in the yields (below 55%, using 50 mM 6APA and PGM) . This problem has been sorted out by using a fed-batch reaction system . By addition of PGM continuously to the reaction mixture (to maintain the concentration between 0.5 and 3 mM), 95% of 6-APA could be transformed to antibiotic (47.5 mM) by only using a 20% excess of acylating ester.

J Clin Neurosci, 2002 Jan, 9(1), 81 - 4
Grisel's syndrome; Guleryuz A et al.; Summary Atlantoaxial subluxation is a rare complication of the upper neck inflammatory processes of head and neck region . Grisel's syndrome is a non-traumatic subluxation of the atlanto axial joint . It is not associated with trauma or bone disease . It typically occurs in children after serious infection in the head and neck region . Several theories have been proposed to explain the pathogenesis of inflammatory subluxation . The primary treatment of Grisel's syndrome is medical . We report a case of atlantoaxial rotatory subluxation treated with external fixation and antibiotic therapy .

Ann Agric Environ Med, 2001, 8(2), 131 - 5
Epizootic situation and risk of rabies exposure in Polish population in 2000, with special attention to Lublin province; Lyczak A et al.; In Poland in 2000 a total of 2,221 cases of animal rabies were reported, including 1,874 (84.4%) of wild animals . The evaluation of epizootic situation in 2000 has shown a few cases of animal rabies in western provinces of Poland, so in regions where a programme aimed at oral vaccination of foxes was introduced . Most cases of animal rabies were identified in the northeastern region, as well as in eastern and central Poland . In October 2000 in Warminsko-Mazurskie province (northeastern region of Poland) rabies was responsible for the death of 59-year-old woman, bitten by a rabid cat, and refused post-exposure specific antirabies prophylaxis . Among domestic animals, the highest incidence of rabies occurred in cattle--167 cases (7.5%), cats--113 (5.1%) and dogs--61 (2.7%) . In the group of wild animals, red foxes accounted for 1,587 (71.5%) cases, raccoon dogs for 210 (9.5%) and martens for 36 (1.6%) . People have been vaccinated against rabies in all provinces of Poland . The number of people vaccinated against rabies in regions adjoining the western border was much smaller compared to other provinces of Poland . The highest rates of using post-exposure prophylaxis occurred in northeastern regions of Poland (Warminsko-Mazurskie province) and eastern and central parts of Poland . On the basis of analysis of cases consulted in the dispensary of rabies prophylaxis in the Department of Infectious Diseases in Lublin, it can be concluded that the number of people with exposure to rabid animals is rather small . Most vaccinations are carried out when animals suspected of being rabid bite patients . These are primarily domestic animals--dogs and cats.

Arch Otolaryngol Head Neck Surg, 2001 Nov, 127(11), 1347 - 50
Efficacy and quality-of-life impact of adult tonsillectomy; Bhattacharyya N et al.; OBJECTIVE: To determine the quality-of-life impact and overall efficacy of adult tonsillectomy for chronic tonsillitis . DESIGN: Cross-sectional survey analysis of patients at least 1 year after undergoing adult tonsillectomy . INTERVENTIONS AND OUTCOME MEASURES: The Glasgow Benefit Inventory was used to quantify the health benefit of tonsillectomy . Data were collected for demographics and antibiotic use, physician visits, and workdays missed due to chronic tonsillitis for the 12 months before and after tonsillectomy . RESULTS: Sixty-five patients returned completed surveys . Mean age was 27.3 years, and mean follow-up was 42.6 months . The improvements in the total score (+27.1), general health subscore (+34.7), social functioning subscore subscore (+14.4), and physical functioning subscore (+9.5) of the Glasgow Benefit Inventory were each statistically significant (P<.001), indicating a significant health benefit of tonsillectomy . Statistically significant decreases in mean weeks receiving antibiotics (-7.8 weeks), mean physician visits (-5.4), and mean workdays missed (-6.3 days) were noted after tonsillectomy (P<.001) . CONCLUSIONS: Adult tonsillectomy provides a significant quality-of-life improvement for patients with chronic tonsillitis . Tonsillectomy also affords decreases in medical resource utilization and missed workdays after tonsillectomy . Such factors should be incorporated into decision making when considering tonsillectomy.

Pneumologie, 2001 Dec, 55(12), 563 - 7
{Tracheobronchopathia osteochondroplastica: an uncommon cause of retention pneumonia in an elderly patient}; Sutor GC et al.; A 79 years old patient without preexisting pulmonary disease was admitted due to pneumonia and hemoptysis . Despite intravenous antibiotic therapy he did not recover and still suffered from fever and dyspnea six days later . Fiberoptic bronchoscopia was performed in order to exclude poststenotic pneumonia . However, macroscopically a "rock-garden" trachea, the characteristic picture of osteochondroplastic tracheobronchopathy, was seen with multiple whitish irregularly shaped nodules in the trachea, except in the pars membranacea, involving both sides of the bronchial system and producing subtotal stenosis . Although cytologic examination suggested adenocarcinoma, histology confirmed the diagnosis of osteochondroplastic tracheobronchopathy . Repeated CT scans as well as control bronchoscopy served as a means of excluding simultaneous carcinoma . The case presented here demonstrates that even progressive tracheobronchopathy may remain asymptomatic for a long time until subtotal stenosis or impaired clearing mechanisms may lead to retention pneumonia . Cytologic examination may give false positive results suggesting malignant disease . However the typical macroscopic picture as well as histology should lead to the correct diagnosis.

Environ Mol Mutagen, 2001, 38(2-3), 216 - 22
Transfection of nonmelanocytic cells with tyrosinase gene constructs for survival studies; Kaur J et al.; To better understand the role of melanin in the response of cells to radiation, the vector pcTYR containing the tyrosinase cDNA and a control vector pcTYW with no tyrosinase cDNA were transfected and expressed in nonpigmented CHOK1-A(L) 1282B5 cells . A pigmented clone was selected from the pcTYR transfectants and an antibiotic-resistant clone was selected from the controls . Melanin was assessed qualitatively by electron paramagnetic resonance (EPR) and quantitatively by a 14C-based assay . The EPR signal detectable in pcTYR-containing cells was at least twice that of pcTYW and parental CHOK1-A(L) cells and the tyrosinase activity was found to be at least six times greater . Melanin was classified to be eumelanin . Survivals of the transfectants were compared to those of the parent cells after irradiation by UVC from a germicidal lamp, UVB from TL01 lamps, UVA from Alisun lamps, UVB/UVA from FS20 lamps, and by gamma-rays from a 137Cs source . Compared to the pcTYW-containing cells, the pigmented cells were more sensitive to killing by UVC, and resistant to killing by UVA and gamma-rays . There were no significant differences in survival after the other irradiations . These results suggest that the pigment synthesized by the activity of tyrosinase alone, unmodified by the activities of TRP1 and TRP2, is protective against the types of reactive oxygen species produced by UVA and gamma-rays but not protective against lethal damage from photons in the UVB range and sensitizes to UVC photons .

Teratology, 2001 Nov, 64(5), 276 - 81
Teratogen update: Lyme disease; Elliott DJ et al.; We reviewed the world literature concerning the reproductive effects of Lyme disease (LD) . Borrelia burgdorferi, which is the etiology of LD, is a spirochete and, as such, may share the potential for causing fetal infection, which may occur in the setting of maternal spirochetemia . Information concerning the effects of gestational LD derives from case reports and series, epidemiologic studies, and experimental animal models . Although provocative, these studies fail to define a characteristic teratogenic effect . However, skin and cardiac involvement have predominated in some reports . Pregnancy wastage has been suggested primarily by animal studies . Gestational LD appears to be associated with a low risk of adverse pregnancy outcome, particularly with appropriated antibiotic therapy . Suggestions for management of clinical situations are presented .

Biopolymers, 2001, 62(5), 278 - 94
FTIR study of five complex beta-lactam molecules; Gil M et al.; Five monocyclic 4-benzoyl-4-phenyl-beta-lactam derivatives in carbon tetrachloride solutions were studied by FTIR spectroscopy . The Fourier self-deconvolution method was applied to enhance the resolution of the FTIR spectra . The calculated spectra of these five compounds, which were obtained by quantum mechanical methods, were compared with FTIR data . A complete assignment of the vibrational frequencies in the 4000-400 cm(-1) range was made . Several vibrations were selected as being useful to characterize the beta-lactam ring . Substituents on N1 (p-methoxyphenyl) and C3 (methyl, phenyl, maleimidyl, and phthalimidyl) on the beta-lactam ring increase the amide resonance and the planarity of the ring . The optimized geometry along with the total electric charges on the four atoms of the ring support an antibiotic action mechanism by a nucleophilic attack of the enzymes on the carbonyl carbon atom of the beta-lactam ring .

Urology, 2001 Dec, 58(6), 1049 - 52
Corporoplasty using pericardium allograft (tutoplast) with complex penile prosthesis surgery; Palese MA et al.; Penile prosthesis implantation can be challenging for such presentations as penile fibrosis and prosthesis erosion and conditions in which the corporal body is severely damaged or deficient . The technical complexity of some repairs and the infections associated with synthetic graft materials will sometimes pose limitations to using these materials . We offer a new role for Tutoplast processed pericardial allograft for complex corporoplasty during penile prosthesis surgery.

Anim Reprod Sci, 2001 Dec 3, 68(3-4), 219 - 28
Management and fertility of mares bred with frozen semen; Samper JC; Semen quality, mare status and mare management during estrus will have the greatest impact on pregnancy rates when breeding mares with frozen semen . If semen quality is not optimal, mare selection and reproductive management are crucial in determining the outcome . In addition to mare selection, client communication is a key factor in a frozen semen program . Old maiden mares and problem mares should be monitored for normal cyclicity and all, except young maidens, should have at least a uterine culture and cytology performed . Mares with positive bacterial cultures and cytologies should be treated at least three consecutive days when in estrus with the proper antibiotic . With frozen semen, timing the ovulation is highly desirable in order to reduce the interval between breeding and ovulation . The use of ovulation inducing agents such as human chorionic gonadotropin (hCG) or the GnRH analogue, deslorelin, are critical components to accurately time the insemination with frozen semen . Most hCG treated mares ovulate 48h post-treatment (12-72h) while most deslorelin (Ovuplant) treated mares ovulate 36-42h post-treatment . However, mares bred more than once during the breeding cycle appear to have a slight but consistent increase in pregnancy rate compared to mares bred only once pre- or post-ovulation . In addition, the "capacitation-like" changes inflicted on the sperm during the process of freezing and thawing appear to be responsible for the shorter longevity of cryopreserved sperm . Therefore, breeding closer to ovulation should increase the fertility for most stallions with frozen semen . Recent evidence would suggest that breeding close to the uterotubal junction increases the sperm numbers in the oviduct increasing the chances of pregnancy . Post-breeding examinations aid in determining ovulation and uterine fluid accumulations so that post-breeding therapies can be instituted if needed . Average pregnancy rates per cycle of mares bred with frozen semen are between 30 and 40% with a wide range between sires . Stallion and mare status are major factors in determining the success of frozen semen inseminations . Pregnancy rates are lower for barren and old maiden mares as well as those mares treated for uterine infections during the same cycle of the insemination . To maximize fertility with frozen semen, a careful selection of the stallions and mares, with proper client communication is critical . Dedication and commitment of mare owner and inseminator will have the most significant impact on the pregnancy rates.

Acta Pharmacol Sin, 2001 May, 22(5), 469 - 74
Demethylation metabolism of roxithromycin in humans and rats; Li XQ et al.; AIM: To investigate the demethylated metabolites of roxithromycin (RXM) in humans and rats, and to study the antibiotic activity of these metabolites in vitro . METHODS: The demethylated metabolites of RXM in humans and in rats were identified by liquid chromatography-mass spectrometry (LC-MS), and the in vitro antibiotic activities of them against three standard strains were also studied compared with those of the parent drug and some other metabolites of RXM . RESULTS: O-Demethylation of RXM was one of the main metabolic routes of RXM in humans, whereas N-demethylation metabolism was more predominant in rats . O-Demethyl-RXM appeared to be equally effective with RXM . CONCLUSION: The O-demethyl-RXM was an active metabolite in humans, and there were some species differences in RXM demethylation metabolism between humans and rats.

J Vasc Surg, 2001 Dec, 34(6), 1055 - 9
Endovascular repair of bleeding aortoenteric fistulas: a 5-year experience; Burks JA Jr et al.; PURPOSE: Aortoenteric fistula (AEF) is an uncommon but catastrophic complication that can occur either primarily or after aortic reconstruction . Untreated, it is uniformly fatal . Conventional surgical management is associated with a perioperative mortality rate of 25% to 90% and frequent major complications . We reviewed our experience with the endovascular treatment of both primary and secondary AEFs in an effort to determine whether endovascular repair is a less morbid alternative to traditional surgical treatment in select patients . METHODS: In a 5-year period, seven high-risk patients who had bleeding and an AEF documented by means of radiology or endoscopy (2 primary, 5 secondary) were treated with coil embolization (1) or placement of an endovascular aortic stent graft (3 aortouniiliac, 2 tube, 1 bifurcated) . One patient underwent computed tomography (CT)-guided percutaneous catheter drainage of an infected perigraft collection . The average follow-up period was 27 months (range, 11-66 months), and follow-up consisted of physical examination, complete blood count, and contrast-enhanced helical CT scanning at 3, 6, and 12 months and yearly thereafter . All patients were treated with intravenous antibiotics perioperatively and were prescribed life-long oral antibiotics on discharge . RESULTS: There was one perioperative death (14%) caused by fungal sepsis . Persistent sepsis after stent-graft placement necessitated laparotomy and bowel resection in one patient . One patient had three bouts of recurrent sepsis that were successfully treated with a change of antibiotic . There were three late deaths (43%) unrelated to the procedure or AEF . Three patients (43%) were alive and well an average of 36 months (range, 23-67 months) after the procedure, with no clinical or radiologic evidence of recurrent bleeding or infection . CONCLUSION: Endovascular management of AEFs is technically feasible and may be the preferred treatment in select patients with bleeding and no signs of sepsis . In the setting of gross infection, it may also be considered in high-risk patients as a bridge to more definitive treatment after hemodynamic stabilization and optimization.

J Urol, 2002 Jan, 167(1), 300 - 4
The ultimate challenge of cloacal exstrophy; Schober JM et al.; PURPOSE: Our review addresses the various system abnormalities associated with cloacal exstrophy and revisits the question of gender assignment . Gender assignment decisions and psychological aspects of gender issues have become the "ultimate challenge." Exploration of gender identity, gender role behavior and sexual orientation has just begun . MATERIALS AND METHODS: A comprehensive literature review was performed with all world literature regarding the current management of cloacal exstrophy . Research focused on management principles, outcomes and documentation of concurrent anomalies . We also describe original research evaluating gender identity in our own series of patients raised as girls to illustrate the challenge of treatment and augment the available literature, which is scant . RESULTS: Abnormalities of the vertebral column ranged from hemivertebra to myelomeningocele . With magnetic resonance imaging, the incidence of spinal dysraphism approached 100% and cord tethering was also more frequently recognized . For children with the short bowel syndrome, advances in antibiotic usage, and parenteral and enteral nutrition have increased the survival rate and reduced morbidity . A neurological component has been recognized for bladder function, bladder neck continence, lower extremity function and erectile capacity . Mitrofanoff-type reconstruction with bladder neck closure and continent catheterizable stoma dramatically increased continence . Diminutive or absent penis has been documented in 30% of males, and no documentation of paternity exists . The majority of females have bicornuate uterus . However, ovaries and tubes were generally normal . No reports of proven fertility exist . CONCLUSIONS: The strategy and timing of surgery relating to gender assignment remain controversial . A desperate need exists for research focusing on gender development and quality of life . Until that time, a cautious watchful approach may be most appropriate as our patients with cloacal exstrophy mature into adulthood.

J Neurosci Methods, 2002 Jan 15, 113(1), 41 - 9
A chamber and artificial dura method for long-term optical imaging in the monkey; Chen LM et al.; Optical imaging over extended periods of time in non-human primates presents serious challenges because the dura mater must be removed to expose the cortical surface . We present a novel nylon imaging chamber with a transparent artificial dura implant, which allows repeated, long-term optical recordings from the cortex . The cylinder of the chamber is inserted into a cranial trephination and held in place with a minimum of screws and acrylic cement . A round patch of artificial dura with a perpendicular wall protects the cortical surface and slows re-growth of dural tissue within the chamber . A cap, manufactured from the same material as the cylinder, is screwed into the chamber and seals it completely . Over a period of 1-4 months, the chamber required a minimum of maintenance and stayed infection-free without local antibiotic application . We repeatedly performed optical imaging in the same animal with the advantages of shortened preparation time . To permit precise alignment and comparison of maps obtained from different imaging sessions, we developed a program that calculated a 2-dimensional spatial transformation between maps of different magnifications, translations, and distortions . We suggest that these methods provide a practical solution to long-term optical imaging in the anesthetized or alert monkey . The exclusive use of non-metallic materials offers the benefit of a lighter and more compact implant, and the possibility to perform MRI scans after chamber implantation.

Minerva Pediatr, 2001 Dec, 53(6), 577 - 9
{Brucellosis and splenic infarction: a case in pediatric age}; Ruggeri C et al.; Splenic infarction has been associated with haematologic and tromboembolic disorders and, more rarely, with infectious diseases . A case of splenic infartion during an attack of brucellosis is reported . Symptoms included persistent left upper quadrant pain and fever . An abdomen scan confirmed the presence of a triangular area of hypodensity in the spleen . Serum and culture exams confirmed the diagnosis of brucellosis . The patient recovered once a course of antibiotic therapy was completed, after 2 and half months.

Drug Saf, 2001, 24(12), 903 - 20
A comparison of liposomal formulations of doxorubicin with drug administered in free form: changing toxicity profiles; Waterhouse DN et al.; The anthracycline antibiotic doxorubicin has wide activity against a number of human neoplasms and is used extensively both as a single agent and in combination regimens . In addition to the use of free, unencapsulated doxorubicin, there are two US Food and Drug Administration approved liposomal formulations of doxorubicin currently available, with several additional liposomal formulations being researched either in the laboratory or in clinical trials . The two approved liposomal formulations of doxorubicin have significantly different lipid compositions and loading techniques, which lead to both unique pharmacokinetic and toxicity profiles, distinct from those of the unencapsulated form . This article discusses the toxicities associated with the free form of doxorubicin, as well as those associated with the two most common liposomal formulations, namely Doxil and Myocet . One of the key toxicity issues linked to the use of free doxorubicin is that of both an acute and a chronic form of cardiomyopathy . This is circumvented by the use of liposomal formulations, as these systems tend to sequester the drug away from organs such as the heart, with greater accumulation in liver, spleen and tumours . However, as will be discussed, the liposomal formulations of doxorubicin are not without their own related toxicities, and, in the case of Doxil, may be associated with the unique toxicity of palmar-plantar erythrodysaesthesia . Overall, the use of liposomal doxorubicin allows for a greater lifetime cumulative dose of doxorubicin to be administered, however acute maximal tolerated doses differ significantly, with that of Myocet being essentially equivalent to free doxorubicin, while higher doses of Doxil may be safely administered . This review highlights the differences in both toxicity and pharmacokinetic properties between free doxorubicin and the different liposomal formulations, as have been determined in pre-clinical and clinical testing against a number of different human neoplasms . The need for further testing of the liposomal formulations prior to the replacement of free doxorubicin with liposomal doxorubicin in any established combination therapy regimens, as well as in combination with the newer therapeutics such as monoclonal antibodies is also discussed.

J Am Chem Soc, 2001 Dec 12, 123(49), 12127 - 34
Alamethicin-leucine zipper hybrid peptide: a prototype for the design of artificial receptors and ion channels; Futaki S et al.; In this report, we describe a novel concept of extramembrane control of channel peptide assembly and the eventual channel current modulation . Alamethicin is a peptide antibiotic, which usually forms ion channels in various association states . By introducing an extramembrane leucine zipper segment (Alm-LeuZ), the association number of alamethicin was effectively controlled to produce a single predominant channel open state . The assembly was estimated to be a tetramer, by comparison of the channel conductance with that of the template-assembled Alm-LeuZ tetramer, which was prepared by the conjugation of a maleimide-functionalized peptide template with cysteine-derivatized Alm-LeuZ segments . Employment of an extramembrane segment of a random conformation provided higher levels of channel conductance . The result exemplified the possibility of channel current control by a conformational switch of the extramembrane segments.

Nephrol Dial Transplant, 2001 Dec, 16(12), 2348 - 56
Candidaemia in patients with dialysis-dependent acute renal failure: aetiology, predisposing and prognostic factors; Sung JM et al.; BACKGROUND: Infections remain the major cause of death among patients with acute renal failure (ARF), especially in severe ARF necessitating dialysis therapy (ARF(d)) . Although the clinical features and outcomes of candidaemia in various patient populations have been described, data concerning candidaemic episodes among patients with ARF(d) are scarce . This study investigated the aetiology, predisposing, and prognostic factors for candidaemia in the ARF(d) patient population . Three patient groups were investigated in this study . METHODS: During an 8-year study period from January 1992 to December 1999, 37 candidaemic episodes that developed among 653 ARF(d) patients were assigned to ARF(d) candidaemic group, and 170 candidaemic episodes developing in patients without ARF(d) or chronic uraemia as the non-ARF(d) candidaemic group, and 28 matched ARF(d) patients without candidaemia were assigned to the ARF(d) control group . Among these groups, clinical characteristics in ARF(d) candidaemia patients, predisposing factors, and outcomes were compared . Four management strategies including central catheter removal, anti-fungal therapy, both, or neither were applied . The prognostic factors for attributable death were evaluated by univariate analysis followed by the multivariate logistic regression analysis . RESULTS: The proportion of ARF(d) patients with candidaemia was significantly higher than in patients who had no ARF(d) or chronic uraemia (5.7% vs 0.15%, P<0.001) . Compared with the non-ARF(d) candidaemic group, systemic lupus erythematosus (SLE), administration of corticosteroid, and central venous catheter-associated candidaemia were more common in the ARF(d) candidaemic group (P<0.05) . In matched case-control study, multiple antibiotic usage was shown to be a predisposing factor for developing candidaemia in patients with ARF(d), and corticosteroid therapy has a marginal significance (P=0.059) . The occurrence of candidaemia increased the mortality rate of ARF(d) (71% vs 39.2% in ARF(d) control group, P<0.05) . By multivariate logistic analysis, the variables associated with attributable death in ARF(d) candidaemic group were identified to be an APACHE II score of >or=18, and anti-fungal therapy for >48 h . Central venous catheters were removed in 32 (86.5%) of the 37 ARF(d) candidaemic patients, among whom the 18 patients who had received anti-fungal therapy for >48 h had a lower attributable death rate than those patients who had not (27.8% vs 64.3%, P<0.05) . Of the remaining five patients who did not have their catheter removed, three patients subsequently died and two patients improved only after catheter removal . CONCLUSIONS: The higher prevalence of candidaemia in ARF(d) patients is due to their underlying illnesses and multiplicity of predisposing factors, rather than ARF and dialysis therapy per se . Predisposing factors include SLE, indwelling central venous catheter, multiple antibiotic usage, and corticosteroid therapy . Prompt anti-fungal therapy and catheter removal should be mandatory for ARF(d) patients with candidaemia.

J Antimicrob Chemother, 2001 Dec, 48(6), 775 - 9
Antifungal properties of selective serotonin reuptake inhibitors against Aspergillus species in vitro; Lass-Florl C et al.; This study investigated the fungicidal activity of selective serotonin reuptake inhibitors (SSRIs) against clinical isolates of Aspergillus fumigatus (n = 11), Aspergillus flavus (n = 9), Aspergillus terreus (n = 10) and Candida parapsilosis (ATCC 22019) . The common drugs fluoxetine, seroxate, sertraline, paroxetine and reboxetine were applied in a broth microdilution test . In addition, we examined whether a post-antibiotic effect occurs following short exposure to the drugs . The various SSRIs showed time- and dose-dependent effects and were fungicidal towards the organisms tested . Sertraline and fluoxetine were the most active drugs, yet there were differences in the susceptibility of the various isolates tested . A lag of regrowth was dependent on the various SSRIs tested and their concentration . Treatment for 4 h at concentrations of sertraline below and equipotent to the minimal fungicidal concentration resulted in a lag of regrowth of 8-24 h for isolates of A . fumigatus and A . flavus . In conclusion, our in vitro studies clearly demonstrate antifungal effects of SSRIs . Animal studies are needed to evaluate the potential role of these psychotropic drugs in the management of fungal infections.

Gene, 2001 Nov 28, 279(2), 165 - 73
A repressor-response regulator gene pair controlling jadomycin B production in Streptomyces venezuelae ISP5230; Yang K et al.; A second regulatory gene (jadR(1)) is located immediately upstream of the putative repressor gene (jadR(2)) in the jad cluster for biosynthesis of the antibiotic jadomycin B in Streptomyces venezuelae ISP5230 . It encodes a 234-amino acid polypeptide with a sequence resembling those of response regulator proteins in two-component control systems . Features in the conserved C-terminal domain of JadR(1) place the protein in the OmpR-PhoB subfamily of response regulators . In mutants where jadR(1) was deleted or disrupted, jadomycin B was not produced, implying that the gene has an essential role in biosynthesis of the antibiotic . Cloning jadR(1) from S . venezuelae in pJV73A, and introducing additional copies of the gene into the wild-type parent by plasmid transformation gave unstable strains with pJV73A integrated into the chromosome . The transformants initially showed increased production of jadomycin B but gave lower titers as excess copies of jadR(1) were lost; mature cultures stabilized with a wild-type level of antibiotic production . The mutant from which jadR(1) had been deleted could not be transformed with pJV73A . Altering the composition of jadR genes in the chromosome by integration of vectors carrying intact and disrupted copies of jadR(1) and jadR(2) provided evidence that the two genes form a regulatory pair different in function from previously reported two-component systems controlling antibiotic biosynthesis in streptomycetes.

Clin Infect Dis, 2002 Jan 1, 34(1), 22 - 7 Epub 2001 Nov 21.
The serological response of patients infected with the agent of human granulocytic ehrlichiosis; Bakken JS et al.; To characterize the serological response in humans to human granulocytic ehrlichiosis (HGE), we prospectively observed 152 patients for as long as 42 months . HGE was confirmed by detection of morulae in blood smears, polymerase chain reaction, blood culture, or a combination of these tests for 94 patients (62.3%), and 92 (97.8%) of the patients had specific serum antibodies thereafter . One hundred twenty-six (99.2%) of 127 patients tested at 1 month were seropositive (89 of 127 patients had seroconversion), and 150 (98.7%) of the 152 patients had become seropositive by 6 months . Eleven patients (7.3%) remained seropositive at 42 months . Neither antibiotic therapy initiated during the first week of illness nor preexisting immunosuppressive conditions abrogated a serological response . Indirect fluorescent antibody testing of acute-phase and convalescent-phase serum samples is a sensitive tool for laboratory confirmation of HGE.

Am J Perinatol, 2001 Nov, 18(7), 397 - 413
Premature rupture of the membranes: an evidence-based approach to clinical care; Naylor CS et al.; Management of the patient with premature rupture of membranes is a relatively common but often perplexing problem frequently faced by the obstetrician . Despite the recent advances in perinatal care, premature membrane rupture, especially in the preterm patient, remains a potentially serious complication with important maternal and fetal implications . This review will address the important questions concerning the management of premature rupture of membranes and will attempt to provide comprehensive answers as they appear in the medical literature.

FEMS Microbiol Lett, 2001 Nov 13, 204(2), 317 - 21
Following the course of human leptospirosis: evidence of a critical threshold for the vital prognosis using a quantitative PCR assay; Truccolo J et al.; In order to follow the course of acute human leptospirosis, an ELISA microtiter plate hybridization method was developed for the quantitative determination of Leptospira spp . in biological samples after PCR . The biotin-labelled amplified product (331 bp from the rrs gene) was hybridized with a complementary capture probe covalently linked onto aminated polystyrene wells, and detected using a colorimetric reaction . The mean detection limit was 50 copies per 10 microl . In a prospective study of human leptospirosis cases, we obtained evidence that a density of 10(4) leptospires per ml of blood is a critical threshold for the vital prognosis of the patients . The practicability of the method makes it suitable for use in tropical areas for multicentric studies . Such studies could lead to a better knowledge of the natural history of the human disease . The method is also suitable for experimental evaluation of improved antibiotic treatments for leptospirosis.

Eur J Pharmacol, 2001 Nov 23, 431(3), 297 - 303
Transport characteristics of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2; Yamaguchi H et al.; Transport characteristics of grepafloxacin and levofloxacin across the apical membrane of Caco-2 cells were examined . Both grepafloxacin and levofloxacin uptakes increased rapidly, and were temperature-dependent . Grepafloxacin and levofloxacin uptakes showed concentration-dependent saturation with Michaelis constants of 3.9 and 9.3 mM, respectively . Uptake of grepafloxacin and levofloxacin increased in Cl(-)-free and ATP depleted conditions, suggesting the involvement of an efflux transport system different from the uptake mechanism . However, cyclosporin A, a typical inhibitor of P-glycoprotein, did not affect the uptake of these drugs . Unlabeled grepafloxacin, unlabeled levofloxacin and quinidine inhibited the uptake of grepafloxacin and levofloxacin under Cl(-)-free conditions . Tetraethylammonium, cimetidine, p-aminohippurate, probenecid, amino acids, beta-lactam antibiotic or monocarboxylates did not inhibit the uptake of grepafloxacin and levofloxacin under the same conditions . In conclusion, our results suggested that grepafloxacin and levofloxacin uptakes were mediated by a specific transport system distinct from those for organic cations and anions, amino acids, dipeptides and monocarboxylates.

Scand J Infect Dis, 2001, 33(10), 776 - 7
Atrial septal defect presenting with Brucella endocarditis; Rahman A et al.; Brucella endocarditis, although a rare complication of brucellosis, is the main case of death attributable to this disease . An atrial septal defect (ASD) presenting with endocarditis in an adult is also extremely rare . We report the case of a male patient who presented with an infective endocarditis and was found to have an ASD . The diagnosis was proven by means of positive serology and isolation of Brucella melitensis from blood cultures and excised vegetation arising from the border of the ASD . The patient was successfully treated by means of excision of the vegetation and specific antibiotic therapy for 3 months.

Parasitol Res, 2001 Nov, 87(11), 973 - 5
Chemotherapeutic approaches to protozoa: Coccidiae--current level of knowledge and outlook; Greif G et al.; Progress in the treatment and prophylaxis of cyst-forming coccidial infections (Neospora, Sarcocystis Toxoplasma) and Cryptosporidium infections has been limited (Table 1: Haberkorn 1996: Croft 1997: Wang 1997) . However, new possibilities have been opened up in the treatment of Eimeria-induced coccidiosis in poultry and mammals . due to improvements in treatment and, or metaphylaxis . A new polyether antibiotic . semduramycin, has recently been added to the range of effective prophylactic preparations . The development of resistance to anticoccidial agents is now posing similar problems to those encountered with malaria, coccidiosis in poultry being particularly affected . Because no new active ingredient from a new family of chemical substances has been developed for more than 10 years, the following approaches are being adopted to get round this problem: the use of older preparations which have not been used for a long time, the introduction of combinations such as narasin nicarbazin or methyl benzoquate clopidol and the alternating use of anticoccidial agents in rotation and shuttle programmes . The goal of a real alternative, i.e . vaccination, has been achieved to a certain extent in the form of live vaccines for laying hens and broiler breeders and is being practiced in some countries.

Int J Clin Pharmacol Ther, 2001 Nov, 39(11), 507 - 12
Drug use and adverse event monitoring in German children; Lewis MA et al.; OBJECTIVE: To assess drug use and the incidence of mild to moderate adverse drug effects (AE) in children aged 0 - 16 years, with 2 different approaches . METHODS: All 185 pediatric practices in the State of Brandenburg, Germany, were surveyed (95% positive response) . A random sample of 50 practices servicing 36,000 children participated in the study as sentinel physicians reporting any AE among their patients . Twenty practices servicing 14,000 children were included in a drug utilization component (DUC) which documented diagnoses, prescribing and AE in all children seen in a 3-month period . RESULTS: The results on the DUC are based on 12,628 children with 26,168 physician contacts, 34,465 diagnoses and 33,140 drug prescriptions given to 85% of the children seen (average age: 6.7 years) . Practice size ranged from 94 to 1,473 children seen in a 3-month period . The average number of physician contacts per child was 2 . 1, with 10% seeing a physician 5 times and more . The diagnoses were respiratory ailments (30%), skin- (12%), injection- (11%) and trauma- (10%) related diagnoses . Major drug uses were respiratory (34% of prescriptions), anti-infective (22%), dermatological (13%), gastrointestinal (9%) and psychotropic agents (8%) . One hundred and fifty-two AE affecting 150 children were documented in the DUC, 60% of these occurring within 3 days after treatment initiation . 83% of AE were mild (up to 4 on a scale from I -6), and 85% were considered by physicians to be attributable . Only 4 reports of very severe events were received . 47% of reports were related to antibiotic uses, 31% to immunizations, 11% to respiratory, and 4% to gastrointestinal agents . While there are no differences in the occurrence of AE by gender, AE decreases significantly by age, maintaining the same patterns of AE type and causative medication . Over a 3-month period, the incidence of mild to moderate ADR in children given medications is estimated as 1,200 per 100,000, or about 1% . CONCLUSIONS: Underreporting of AE remains an issue even when a monitoring scheme suggests compliance . The results of this study show that while AE in children are generally non-serious, 1% of treatments might elicit mild AE leading to a consultation . Direct practice recording produces more reports than a sentinel system.

Z Geburtshilfe Neonatol, 2001 Sep-Oct, 205(5), 167 - 73
{Hematopoietic growth factors in prevention and therapy of infectious complications in premature and newborn infants}; Lehrnbecher T; Bacterial sepsis continues to be an important cause of morbidity and mortality in neonates . Neutropenia in the newborn, as a result of decreased bone marrow neutrophil storage pool reserves and myeloid committed progenitor cells, increases the risk of sepsis and is associated with a poor prognosis . The hematopoietic colony-stimulating factors G-CSF (granulocyte colony stimulating factor) and GM-CSF (granulocyte-macrophage colony stimulating factor) increase the number of circulating neutrophil number by stimulating neutrophil precursors proliferation . In a number of clinical trials in very low birthweight neonates and in neonates with preeclampsia-associated neonatal neutropenia, both hematopoietic growth factors significantly increased the circulating absolute neutrophil count . However, no larger study showed that prophylactic G-CSF or GM-CSF treatment resulted in a reduction of infectious complications or in an improved overall survival . Similar results were seen in studies evaluating G-CSF and GM-CSF as intervention therapy in septic neonates . Therefore, experts do not recommend the routine use of the expensive growth factors in preterm and term neonates . However, prospective clinical trials are still needed to evaluate whether specific treatment groups will benefit from the use of G-CSF or GM-CSF . In this regard, efforts must be directed at better defining the endpoints and in particular assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs . In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups of patients.

Bioinformatics, 2001 Nov, 17(11), 1077 - 83
Database-driven multi locus sequence typing (MLST) of bacterial pathogens; Chan MS et al.; MOTIVATION: Multi Locus Sequence Typing (MLST) is a newly developed typing method for bacteria based on the sequence determination of internal fragments of seven house-keeping genes . It has proved useful in characterizing and monitoring disease-causing and antibiotic resistant lineages of bacteria . The strength of this approach is that unlike data obtained using most other typing methods, sequence data are unambiguous, can be held on a central database and be queried through a web server . RESULTS: A database-driven software system (mlstdb) has been developed, which is used by public health laboratories and researchers globally to query their nucleotide sequence data against centrally held databases over the internet . The mlstdb system consists of a set of perl scripts for defining the database tables and generating the database management interface and dynamic web pages for querying the databases . AVAILABILITY: http://www.mlst.net.

Arch Pediatr Adolesc Med, 2001 Nov, 155(11), 1204 - 9
Limits of the genetic revolution; Scheuerle A; The genetic revolution will touch all disciplines of medicine, much like the antibiotic discoveries in the last century did . However, genetic medicine is not an immediate "magic bullet" for all noninfectious conditions . Despite the sometimes melodramatic announcements by the lay media, there are hurdles to overcome before genetic treatments become as ubiquitous as antibiotics . These barriers fall into 3 categories: molecular, economic, and behavioral . First, the molecular difficulties include the biochemical complexity of genes and genetic disease, variation in pathogenesis among races, and gene-environment interaction . Second, economic disincentive to develop orphan drugs, and the expense of such medications, may hinder production of treatments for truly rare genetic diseases . Third, patients are unlikely to be any more compliant with new medications or recommendations than they are with the current ones . The "magic bullet" of folic acid is not used by the majority of women who are aware of its usefulness in preventing birth defects . While the genetic revolution has much potential, the complexity of genetics itself is difficult and the current barriers to useful treatment will not change . As with oncological and transplantation technology, great strides are likely to be made, but only at a measured pace.

Vet Ophthalmol, 2001 Sep, 4(3), 221 - 5
Phacofragmentation for morgagnian cataract in a horse; Hardman C et al.; A 3-year-old Paint gelding was presented for sudden onset of cataract affecting the right eye . Ophthalmic examination revealed subtle to mild microphthalmia and a mature cataract affecting the right globe . The right eye was treated with an antibiotic-corticosteroid ophthalmic ointment and phacofragmentation was recommended . On re-examination 5 months later, resorption of the cortex of the right lens and a morgagnian cataract were evident . The nucleus was positioned ventronasally in the lens capsule . The right eye had light perception, and a menace response was present . Examination of the right fundus via binocular indirect ophthalmoscopy was not possible . Ophthalmic ultrasonography revealed that the right globe was 4 mm shorter in axial length when compared with the left globe . There was a marked reduction in the size of the right lens vs . the left lens, and the presence of a moderate amount of hyperechoic debris was identified within the vitreal compartment of the right globe . Phacofragmentation, irrigation and aspiration of the morgagnian cataract and an anterior vitrectomy were performed . On postoperative examination, the eye was comfortable and a menace response was present . The horse regained useful vision and continues to have a comfortable, visual eye 7 months postoperatively.

J Org Chem, 2001 Nov 30, 66(24), 8204 - 10
Syntheses of puromycin from adenosine and 7-deazapuromycin from tubercidin, and biological comparisons of the 7-aza/deaza pair; Robins MJ et al.; Protection (O5') of 2',3'-anhydroadenosine with tert-butyldiphenylsilyl chloride and epoxide opening with dimethylboron bromide gave the 3'-bromo-3'-deoxy xylo isomer which was treated with benzylisocyanate to give the 2'-O-(N-benzylcarbamoyl) derivative . Ring closure gave the oxazolidinone, and successive deprotection concluded an efficient route to 3'-amino-3'-deoxyadenosine . Analogous treatment of the antibiotic tubercidin {7-deazaadenosine; 4-amino-7-(beta-D-ribofuranosyl)pyrrolo{2,3-d}pyrimidine} gave 3'-amino-3'-deoxytubercidin . Trifluoroacetylation of the 3'-amino function, elaboration of the heterocyclic amino group into a (1,2,4-triazol-4-yl) ring with N,N'-bis{(dimethylamino)methylene}hydrazine, and nucleophilic aromatic substitution with dimethylamine gave puromycin aminonucleoside {9-(3-amino-3-deoxy-beta-D-ribofuranosyl)-6-(dimethylamino)purine} and its 7-deaza analogue . Aminoacylation {BOC-(4-methoxy-L-phenylalanine)} and deprotection gave puromycin and 7-deazapuromycin . Most reactions gave high yields at or below ambient temperature . Equivalent inhibition of protein biosynthesis in a rabbit reticulocyte system and parallel growth inhibition of several bacteria were observed with the 7-aza/deaza pair . Replacement of N7 in the purine ring of puromycin by "CH" has no apparent effect on biological activity.

Rhinology, 2001 Sep, 39(3), 151 - 5
Endoscopic sinus surgery for orbital subperiosteal abscess secondary to sinusitis; Bhargava D et al.; Subperiosteal orbital abscess (SPA) is a serious complication of paranasal sinusitis, which can lead to blindness or even death . A quick response is necessary as this condition is treatable . Early surgical intervention is indicated if there is risk of visual loss, or if no improvement is observed within 48 hours of starting medical therapy . Three patients with orbital SPA secondary to sinusitis treated successfully by Functional Endoscopic Sinus Surgery (FESS) are presented in this case series . The surgical indications were impending visual loss with an abscess and cellulitis impinging on the optic nerve in one child and in the other two patients, a lack of clinical response within 48 hours after starting systemic antibiotic . CT scans, nasal endoscopy, and ophthalmologic examinations are mandatory during the evaluation process . The advantages of FESS in these patients were the avoidance of external ethmoidectomy and its external facial scar, an early drainage of the affected sinuses, SPA, and the eradication of the disease from the fronto-ethmoidal region leading to an enhanced recovery and a reduced hospital stay . FESS is also a safe, convenient and minimally invasive procedure in patients presenting with serious complications of sinusitis.

J Nat Prod, 2001 Nov, 64(11), 1447 - 50
Isolation and structure determination of novamethymycin, a new bioactive metabolite of the methymycin biosynthetic pathway in Streptomyces venezuelae; Zhang Q et al.; Novamethymycin (9), a novel macrolide antibiotic, was isolated from Streptomyces venezuelae, the producer of methymycin (4) and neomethymycin (5) . Spectroscopic analysis of 9 indicated that it is highly related to 4 and 5 but contains hydroxy groups at both C-10 and C-12 on the macrolactone ring . Bioconversion studies using the PikC cytochrome P450 hydroxylase demonstrated that 4 is converted to 9, further broadening the remarkable substrate flexibility of this enzyme.

Clin Orthop, 2001 Nov, (392), 116 - 23
Use of recombinant human erythropoietin in two-stage total knee arthroplasty for infection; Cushner FD et al.; A multicenter prospective study was conducted to determine whether epoetin alfa could be used to lower transfusion requirements after two-stage exchange arthroplasty for infection . Forty-one consecutive patients undergoing successful two-stage exchange arthroplasty for an infected total knee arthroplasty were enrolled in a prospective study . Epoetin alfa (40,000 units) was administered subcutaneously after prosthesis resection and antibiotic spacer placement . Although there was no difference in the hemoglobin levels before resection arthroplasty or on postoperative Day 3 between the study group and the control group, hemoglobin levels before reimplantation were higher in the patients who received epoetin alfa (12.4 mg/dL; range, 9.3-15.1 mg/dL) compared with the control group (11.3 mg/dL; range, 8.1-14.4 mg/dL) . Average increase in hemoglobin level in the interval between stages was higher in the treatment group (3.2 mg/dL; range, -0.7-6.8 mg/dL) than the control group (1.7 mg/dL; range, -1.9-6 mg/dL) . The transfusion rate decreased from 83% of patients in the control group to 34% in the study group during reimplantation . In addition, overall incidence of transfusion for either stage improved from 89% in the control group to 44% in the patients treated with epoetin alfa . Perioperative epoetin alfa statistically increased the hemoglobin levels and decreased transfusion rates for patients undergoing two-stage revision for infected total knee arthroplasty.

Microbiol Res, 2001, 156(3), 239 - 46
Cloning and partial characterization of the putative rifamycin biosynthetic gene cluster from the actinomycete Amycolatopsis mediterranei DSM 46095; Kaur H et al.; The actinomycete Amycolatopsis mediterranei produces the commercially and medically important polyketide antibiotic rifamycin, which is widely used against mycobacterial infections . The rifamycin biosynthetic (rif) gene cluster has been isolated, cloned and characterized from A . mediterranei S699 and A . mediterranei LBGA 3136 . However, there are several other strains of A . mediterranei which also produce rifamycins . In order to detect the variability in the rif gene cluster among these strains, several strains were screened by PCR amplification using oligonucleotide primers based on the published DNA sequence of the rif gene cluster and by using dEBS II (second component of deoxy-erythronolide biosynthase gene) as a gene probe . Out of eight strains of A . mediterranei selected for the study, seven of them showed the expected amplification of the DNA fragments whereas the amplified DNA pattern was different in strain A . mediterranei DSM 46095 . This strain also showed striking differences in the banding pattern obtained after hybridization of its genomic DNA against the dEBS II probe . Initial cloning and characterization of the 4-kb DNA fragment from the strain DSM 46095, representing a part of the putative rifamycin biosynthetic cluster, revealed nearly 10% and 8% differences in the DNA and amino acid sequence, respectively, as compared to that of A . mediterranei S699 and A . mediterranei LBGA 3136 . The entire rif gene cluster was later cloned on two cosmids from A . mediterranei DSM 46095 . Based on the partial sequence analysis of the cluster and sequence comparison with the published sequence, it was deduced that among eight strains of A . mediterranei, only A . mediterranei DSM 46095 carries a novel rifamycin biosynthetic gene cluster.

Cell Growth Differ, 2001 Nov, 12(11), 543 - 50
Radicicol suppresses transformation and restores tropomyosin-2 expression in both ras- and MEK-transformed cells without inhibiting the Raf/MEK/ERK signaling cascade; Kim PN et al.; The antibiotic radicicol suppresses transformation in a variety of transformed cells . The antineoplastic effects of the drug have been attributed to the degradation of Raf and the inactivation of the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling cascade . Here we demonstrate that radicicol induces cell spreading, suppresses anchorage-independent cell growth, and increases the expression of the high-molecular weight tropomyosin isoform TM-2 in cells stably expressing a constitutively active form of MEK-1 as well as in ras-transformed cells . Furthermore, the reverting effects of the drug are achieved at concentrations below those required to deplete Raf from the cell or to inhibit the phosphorylation of ERK or its substrates Elk and pp90(RSK) . In contrast, low concentrations of radicicol significantly inhibited activator protein (AP-1) and serum response factor (SRF)-mediated transcription . The lack of correlation between the effects of radicicol on cell phenotype and on the signaling activities of the Raf/MEK/ERK pathway indicate that Raf depletion or disruption of proximal signaling events in the mitogen-activated protein kinase pathway are not the predominant mechanisms by which the drug suppresses the transformed phenotype . Our observation that low concentrations of radicicol block transcriptional activities mediated by AP-1 and SRF suggests that interference with signaling upstream of these transcription factors may contribute to the reverting effects of the drug.

Klin Padiatr, 2001 Nov-Dec, 213(6), 343 - 6
{Papilledema and acute bilateral amaurosis accompanying acute sinusitis}; Jungert JM et al.; BACKGROUND: Acute sinusitis can lead to severe complications . This includes involvement of the optical nerve with visual loss and brain abscess as a life-threatening complication . PATIENTS: Empyema of the chiasma opticum region with neuritis nervi optici and bilateral acute amaurosis was observed in a 13 year old boy with sinusitis sphenoidalis and ethmoidalis . In a 11 year old girl, pronounced papilledema was found to be closely associated with sinusitis sphenoidalis . While she recovered completely on appropriate antibiotic therapy, visual loss in the boy was irreversible despite surgical intervention . CONCLUSIONS: Sinusitis should always be considered in patients with impaired vision, neuritis nervi optici or unexplained papilledema, especially if occurring in association with an upper respiratory infection . In addition to physical examination, cranial computer tomography or magnetic resonance imaging of the brain including sinuses and chiasma opticum should be applied early . If empyema is found, immediate surgical intervention is of prognostic importance.

J Pediatr, 2001 Nov, 139(5), 636 - 42
Growth hormone improves clinical status in prepubertal children with cystic fibrosis: results of a randomized controlled trial; Hardin DS et al.; OBJECTIVES: We conducted a 1-year randomized controlled trial to test the hypothesis that growth hormone (GH) improves the clinical status of children with cystic fibrosis . STUDY DESIGN: Nineteen prepubertal children were randomized to control (NonTX, n = 9) or to daily injections of GH (0.3 mg/kg/wk) (GHTX, n = 10) for 1 year . Every 3 months height, weight, and lean tissue mass were measured . Caloric intake, resting energy expenditure, pulmonary function, and respiratory muscle strength were measured every 6 months, as were total number of hospitalizations and courses of outpatient intravenous antibiotics . RESULTS: The GHTX group had significantly greater height, height velocity (NonTX = 3.8 +/- 1.4 cm/y, GHTX = 8.1 +/- 2.4 cm/y; P =.002), weight, weight velocity (NonTX = 2.1 +/- 0.9 kg/y, GHTX = 4.5 +/- 1.1 kg/y; P =.004), and change in lean tissue mass (NonTX = 2.1 +/- 1.6 kg, GHTX = 4.7 +/- 1.7 kg; P =.01) analyzed by the Student t test . The GHTX group had significant improvement in delta forced vital capacity compared with the year before study, and respiratory muscle strength improved . The number of hospitalizations and outpatient intravenous antibiotic courses significantly decreased in the GHTX group but did not change in the NonTX group . No subject had development of cystic fibrosis-related diabetes . CONCLUSIONS: Results of the first randomized controlled trial of GH treatment in cystic fibrosis indicate that GH improves growth and clinical status.

ORL J Otorhinolaryngol Relat Spec, 2001 Nov-Dec, 63(6), 379 - 81
Lacrimal gland abscess: an unusual complication of rhinosinusitis; Mirza S et al.; We report the case of a 72-year-old female suffering from mild myelodysplasia who initially presented with a peri-orbital cellulitis secondary to rhinosinusitis . The pre-septal infection failed to completely resolve despite intensive antibiotic therapy and endoscopic drainage of the sinuses . Computerised tomography revealed a complicating suppuration of the lacrimal gland . Incision and drainage of the lacrimal gland abscess led to a complete resolution of the pre-septal cellulitis . Suppuration of the lacrimal gland is, as far as we are aware, a previously unreported complication of rhinosinusitis . Its presence could be borne in mind when evaluating computerised tomography scans of patients presenting with orbital complications of sinusitis, particularly in the immunocompromised .

Thorax, 2001 Dec, 56(12), 947 - 53
Symptom resolution assessed using a patient directed diary card during treatment of acute exacerbations of chronic bronchitis; Woolhouse IS et al.; BACKGROUND: Acute exacerbations of chronic bronchitis are common and the presenting symptoms vary, although it is not clear how this should influence management . From a health care perspective, an understanding of the speed of symptom resolution is of importance to determine the success of treatment or when a change is indicated because of treatment failure . METHODS: The response of 63 patients treated at home for exacerbations of chronic bronchitis was assessed using a patient directed diary card incorporating sputum characteristics and symptoms . Treatment was given according to the nature of the sputum at presentation; patients with purulent sputum received an antibiotic for 5 or 10 days (randomised, double blind) whereas patients with mucoid sputum received high dose inhaled steroid or placebo for 14 days (randomised, double blind) . RESULTS: The mean (SE) total diary card score at presentation was significantly higher in the purulent group than in the mucoid group (19.7 (0.9) v 16.3 (0.9); mean difference -3.4 (95% CI -6.1 to -0.7), p<0.05) . In the purulent group sputum colour and volume improved rapidly and in both groups the mean (SE) total diary card score had improved by the fifth day of treatment to 13.0 (0.7) in the purulent group (mean difference -6.6 (95% CI -8.8 to -4.4), p<0.001) and 14.6 (0.8) in the mucoid group (mean difference -1.7 (95% CI -4.0 to 0.8), p<0.05), which was no longer significantly different from the stable state . Diary card scores did not differ significantly between patients who received antibiotics for 5 or 10 days in the purulent group or between patients who received inhaled fluticasone or placebo in the mucoid group . CONCLUSIONS: Exacerbations of chronic bronchitis associated with purulent sputum have significantly worse symptoms at presentation than those with mucoid sputum . In both groups these symptoms resolve rapidly so that by the fifth day of treatment they are no different from the stable state . No significant effect was found on symptom resolution of antibiotic duration (5 v 10 days) in the purulent group or of inhaled fluticasone in the mucoid group, which resolved without antibiotics . Larger numbers may be required to demonstrate a statistically (if not clinically) significant difference.

Stem Cells, 2001, 19(6), 522 - 33
Leridistim, a chimeric dual G-CSF and IL-3 receptor agonist, enhances multilineage hematopoietic recovery in a nonhuman primate model of radiation-induced myelosuppression: effect of schedule, dose, and route of administration; Farese AM et al.; Leridistim is from the myelopoietin family of proteins, which are dual receptor agonists of the human interleukin-3 and G-CSF receptor complexes . This study investigated the effect of dosage, administration route, and schedule of leridistim to stimulate multilineage hematopoietic recovery in total body irradiated rhesus monkeys . Animals were x-irradiated on day 0 (600 cGy, 250 kVp) and then received, on day 1, leridistim s.c . in an abbreviated, every-other-day schedule at 200 microg/kg, or daily at 50 microg/kg, or i.v . daily or every-other-day schedules at 200 microg/kg dose . Other cohorts received G-CSF (Neupogen((R)) {Filgrastim}) in an every-other-day schedule at 100 microg/kg/day, or autologous serum (0.1%) s.c . daily . Hematopoietic recovery was assessed by bone marrow clonogenic activity, peripheral blood cell nadirs, duration of cytopenias, time to recovery to cellular thresholds, and requirements for clinical support . Leridistim, administered s.c . every other day, or i.v . daily, significantly improved neutrophil, platelet, and lymphocyte nadirs, shortened the respective durations of cytopenia, hastened trilineage hematopoietic recovery, and reduced antibiotic and transfusion requirements . A lower dose of leridistim administered daily s.c . enhanced recovery of neutrophil and platelet parameters but did not affect lymphocyte recovery relative to controls . Leridistim, a novel engineered hematopoietic growth factor administered at the appropriate dose, route and schedule, stimulates multilineage hematopoietic reconstitution in radiation-myelosuppressed nonhuman primates.

Aust Vet J, 2001 Oct, 79(10), 675 - 9
The diagnosis and treatment of a thoracic abscess in an alpaca; Adolf J et al.; A 6-month-old alpaca presented for lethargy, failure to thrive and leucocytosis . Diagnostic procedures, including thoracic ultrasound, radiographs and a computed tomography scan, were used to document a thoracic mass . Based on appearance and ultrasound-guided aspiration of purulent material, the mass was determined to be a large abscess . The abscess was treated with surgical drainage and long-term antibiotic therapy . The origin of this thoracic abscess was felt to be the caudal mediastinum, secondary to bacterial seeding of the caudal mediastinal lymph nodes . Although an aetiological agent was not definitively determined, the most likely was Actinomyces spp or Arcanobacterium pyogenes . The alpaca made a complete recovery following treatment.

Rocz Akad Med Bialymst, 2000, 45, 184 - 98
Analysis of some peripheral blood lymphocyte subsets in relation to Borrelia burgdorferi antibodies in patients with Lyme disease; Zajkowska JM et al.; The aim of our study was to evaluate the changes in T (CD3), B(CD19) lymphocytes, CD4 and CD8 subsets, activated CD3+ HLA-DR+ lymphocytes, lymphocytes with receptor for IL-2 (CD3+CD25), NK cells as well as the rate of CD4/CD8 in 30 patients with recognized Lyme disease, before and after antibiotic therapy . Patients were divided into the following groups: Group I n = 9--without detected specific antibodies against B . burgdorferi and with clinical recognition of EM(erythema migrans) . Group II n = 10--with increased IgM production, with a clinical form of Lyme arthritis and neuroborreliosis . Group III n = 11--with increased IgG anti B . burgdorferi production, with clinical recognition of Lyme arthritis . The results were compared with the results obtained in the control group consisting of 90 healthy people . The measurements were performed in the flow cytometer COULTER EPI XL with Becton Dickinson antibodies . The antibodies against B . burgdorferi were detected by means of ELISA method using Dako, Biomedica and Biocom kits . The statistic analysis was performed with AnStat Program . The changes in lymphocyte subsets were characterised by the decrease in the percentage of CD4, CD8, NK and CD3+HLA-DR+ lymphocytes in peripheral blood before treatment with later tendency to increase . The results show that the lag phase of antibodies production coincides with high activity of lymphocytes (group I) . The significant level of antibodies in IgM class induced by the collaboration of T and B cells was found in the group II . In the group III, in which antibodies in IgG class predominated, the changes in lymphocyte subsets were less intensive . The results of our investigations indicate that the immune response in Lyme disease develops mainly with the participation of both cellular and humoral response which is involved in both the defense against and the pathogenesis of the disease.

J Am Acad Dermatol, 2001 Dec, 45(6), 857 - 62
Recombinant human platelet-derived growth factor gel speeds healing of acute full-thickness punch biopsy wounds; Cohen MA et al.; BACKGROUND: Recombinant human platelet derived growth factor-BB gel (PDGF gel) has been shown to be effective in the treatment of diabetic neuropathic ulcers . It is also being used off-label to speed wound healing of flaps, grafts, and wounds from Mohs micrographic surgery . OBJECTIVE: The purpose of the study was to compare the rate of healing in wounds treated with PDGF gel and with wounds treated with conventional therapy (antibiotic ointment) . METHODS: A double-blind controlled study of 7 healthy volunteers was performed . With a 4-mm skin punch biopsy instrument, two full-thickness wounds were made on each arm of each volunteer . Fourteen wounds treated with PDGF gel were compared with 14 wounds treated with antibiotic ointment . Healing was evaluated by visual determination of the global percentage healed and wound depth . RESULTS: Wounds treated with PDGF gel showed a significantly faster rate of healing on each of the initial 6 follow-up visits . The greatest difference was on day 10 when PDGF-treated wounds were 71% healed compared with 28% for antibiotic-treated wounds (P =.0005) . At days 22 and 24, 92.9% and 100% of the PDGF gel-treated wounds were healed, compared with 50% and 57%, respectively (P =.0313 and P =.0313), in the antibiotic ointment group . By day 29, both PDGF gel and antibiotic-treated wounds were healed . PDGF also decreased wound depth compared with wounds treated with antibiotic ointment at days 8 and 10 with P values <.0313 and <.0020, respectively . CONCLUSION: We conclude that PDGF gel speeds healing of acute full-thickness wounds compared with antibiotic ointment.

J Clin Oncol, 2001 Nov 15, 19(22), 4245 - 51
Prospective study of Helicobacter pylori eradication therapy in stage I(E) high-grade mucosa-associated lymphoid tissue lymphoma of the stomach; Chen LT et al.; PURPOSE: High-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are generally believed to be Helicobacter pylori-independent, autonomously growing tumors . However, anecdotal cases of regression of high-grade lymphomas after the cure of H pylori infection had been described . The present prospective study was conducted to evaluate the effect of anti-H pylori therapy in stage I(E) high-grade gastric MALT lymphomas . PATIENTS AND METHODS: Sixteen patients with H pylori infection and stage I(E) gastric high-grade MALT lymphoma consented to a brief antibiotic therapy as first-line treatment from June 1995 through April 2000 . Then, patients underwent intensive endoscopic follow-up examinations (+/- endoscopic ultrasonography) with biopsy to evaluate tumor response . Patients with significant improvement of gross lesions that accompanied regression of large cells were followed up without additional treatment . Patients without significant improvement were immediately referred to systemic chemotherapy . RESULTS: Eradication of H pylori was achieved in 15 patients and was accompanied by rapid gross tumor regression and disappearance of large cells in 10 . All 10 of these patients with early response had subsequent complete histologic remission of lymphoma . The complete remission rate was 62.5% (95% confidence interval, 35.8% to 89.1%) . The response rate was not affected by the tumor grading (proportion of large blast cells within the tumor) but was adversely affected by the depth of tumor invasion . At a median follow-up of 43.5 months (range, 21.1 to 67.4 months), all 10 of these patients remained lymphoma-free . The median duration of complete response was 31.2 months (range, 14.4 to 49.1 months) . CONCLUSION: These results suggest that high-grade transformation is not necessarily associated with the loss of H pylori dependence in early-stage MALT lymphomas of the stomach.

J Biol Chem, 2002 Feb 1, 277(5), 3219 - 25 Epub 2001 Nov 13.
Transition state analogue inhibitors of purine nucleoside phosphorylase from Plasmodium falciparum; Kicska GA et al.; Immucillins are logically designed transition-state analogue inhibitors of mammalian purine nucleoside phosphorylase (PNP) that induce purine-less death of Plasmodium falciparum in cultured erythrocytes (Kicska, G . A., Tyler, P . C., Evans, G . B., Furneaux, R . H., Schramm, V . L., and Kim, K . (2002) J . Biol . Chem . 277, 3226-3231) . PNP is present at high levels in human erythrocytes and in P . falciparum, but the Plasmodium enzyme has not been characterized . A search of the P . falciparum genome data base yielded an open reading frame similar to the PNP from Escherichia coli . PNP from P . falciparum (P . falciparum PNP) was cloned, overexpressed in E . coli, purified, and characterized . The primary amino acid sequence has 26% identity with E . coli PNP, has 20% identity with human PNP, and is phylogenetically unique among known PNPs with equal genetic distance between PNPs and uridine phosphorylases . Recombinant P . falciparum PNP is catalytically active for inosine and guanosine but is less active for uridine . The immucillins are powerful inhibitors of P . falciparum PNP . Immucillin-H is a slow onset tight binding inhibitor with a K(i)* value of 0.6 nm . Eight related immucillins are also powerful inhibitors with dissociation constants from 0.9 to 20 nm . The K(m)/K(i)* value for immucillin-H is 9000, making this inhibitor the most powerful yet reported for P . falciparum PNP . The PNP from P . falciparum differs from the human enzyme by a lower K(m) for inosine, decreased preference for deoxyguanosine, and reduced affinity for the immucillins, with the exception of 5'-deoxy-immucillin-H . These properties of P . falciparum PNP are consistent with a metabolic role in purine salvage and provide an explanation for the antibiotic effect of the immucillins on P . falciparum cultured in human erythrocytes.

J Am Chem Soc, 2001 Nov 21, 123(46), 11376 - 80
A new mode of stereochemical control revealed by analysis of the biosynthesis of dihydrogranaticin in Streptomyces violaceoruber Tü22; Taguchi T et al.; A class of Streptomyces aromatic polyketide antibiotics, the benzoisochromanequinones, all shows trans stereochemistry at C-3 and C-15 in the pyran ring . The opposite stereochemical control found in actinorhodin (3S, 15R, ACT) from S . coelicolor A3(2) and dihydrogranaticin (3R, 15S, DHGRA) from S . violaceoruber Tu22 was studied by functional expression of the potentially relevant ketoreductase genes, actIII, actVI-ORF1, gra-ORF5, and gra-ORF6 . A common bicyclic intermediate was postulated to undergo stereospecific reduction to provide either the 3-(S) or the 3-(R) configuration of an advanced intermediate, 4-dihydro-9-hydroxy-1-methyl-10-oxo-3-H-naphtho{2,3-c}pyran-3-acetic acid (DNPA) . Combinations of the four ketoreductase genes were coexpressed with the early biosynthetic genes encoding a type II minimal polyketide synthase, aromatase, and cyclase . gra-ORF6 was essential to produce (R)-DNPA in DHGRA biosynthesis . Out of the various recombinants carrying the relevant ketoreductases, the set of gra-ORF5 and -ORF6 under translational coupling (on pIK191) led to the most efficient production of (R)-DNPA as a single product, implying a possible unique cooperative function whereby gra-ORF6 might encode a "guiding" protein to control the regio- and stereochemical course of reduction at C-3 catalyzed by the gra-ORF5 protein . Updated BLAST-based database analysis suggested that the gra-ORF6 product, a putative short-chain dehydrogenase, has virtually no sequence homology with the actVI-ORF1 protein, which was previously shown to determine the 3-(S) configuration of DNPA in ACT biosynthesis . This demonstrates an example of opposite stereochemical control in antibiotic biosynthesis, providing a key branch point to afford diverse chiral metabolic pools.

Acta Chir Orthop Traumatol Cech, 2001, 68(1), 31 - 8
{Arthroscopic treatment of the unstable knee joint by ligament reconstruction using allografts}; Pasa L et al.; PURPOSE OF THE STUDY: Recurring and multidirectional instability of the knee joint is a therapeutic problem mainly due to a limited possibility of harvesting grafts for its treatment . The authors present the methodology of the solution of recurring and multidirectional instabilities of the knee joint by means of allografts . They inform about the technique of harvesting and preservation of grafts and include the necessary examinations and early results . MATERIAL: Due to the above mentioned reasons the authors concentrated on the possibility of harvesting grafts for ligamentoplasty from donors . They developed the technique of harvesting, examination and preservation of allografts and their application by arthroscopy both in recurring and multidirectional instability . They used grafts from lig . patellae and m . quadriceps femoris . In the group of 21 patients operated on they used allograft for ligamentoplasty of 15 anterior cruciate ligaments (ACL) and 9 posterior cruciate ligaments (PCL), (4 times multidirectional instability of ACL + PCL, 14 times patellar tendon and 10 times tendon of m . quadriceps femoris) . METHODS: Harvesting of grafts for ligamentoplasty from donors, examination according to EATB rules, preservation at the temperature of -80 degrees C . Prior to the application an antibiotic bath for 10 minutes . Application of grafts by arthroscopy, for ACL the grafts were used from patellar tendon and m . quadriceps femoris, for PCL the grafts from m . quadriceps femoris anchored in two channels . Operation in multidirectional instabilities in one step procedure--ACL, PCL and posterolateral capsular complex . Fixation by orthesis for 6-8 weeks according to the type of operation, early physiotherapy starting from 2nd day after operation . RESULTS: No differences were found in the postoperative course (immune or any other reaction) in comparison with autografts (duration of hospitalization, postoperative regime, pain), physiotherapy in the replacement of one ligament is faster in comparison with autografts . Ingrowth of allografts according to radiographs is without any special reaction . Results were evaluated according to Lysholm score and they show a significant improvement as compared to the condition prior to operation . No peroperative and postoperative complications were found . There was no immune reaction after the operation, in all patients there occurred a significant improvement of the stability of the knee joint . The results according to Lysholm score prior to the operation and after the ligamentoplasty show both a subjective and objective improvement after the operation . DISCUSSION: Application of allografts for the reconstruction of recurring and multidirectional instability of the knee joint is a method offering new possibilities . Its advantages include reduction of the duration of surgery, significantly reduced morbidity of the joint operated on, the possibility of adjustment of the graft, if need be . Disadvantages are the following: the possibility of a transfer of a virus disease which can be eliminated by a careful examination of donors; a longer period of graft remodelling, which can be compensated by a correct physiotherapy and postoperative regime . CONCLUSION: Application of allografts in the surgical treatment of instability of the knee joint is suitable in the current period of well developed examinations and surgical techniques . Early results are optimistic . Observation of all rules for the application of allografts will allow to extend in the correct indications the range of the possibilities of surgical treatment of recurring and multidirectional instabilities of the knee joint.

Acta Chir Orthop Traumatol Cech, 2001, 68(3), 141 - 7
{Giant cell tumor--osteoclastoma: part II}; Kordos J Sr et al.; Authors present current views on the comprehensive diagnostics, treatment and prognosis of giant cell tumours . They include an exact algorithm of diagnostics necessary for a timely treatment . They describe an often unexpected behaviour of these tumours which is frequently active and aggressive, to a small extent these tumours show the tendency to become malignant . The treatment prefers curretage, antibiotic irrigation and filling in with bone cement . In case of recurrence and an extensive process, block resection and replacement by an individual implant, in hardly accessible locations (spine, sacrum, pelvis) or radiotherapy is recommended . The authors present in detail results of a 10-year systematic follow-up of 56 patients, of which 61.6% were in active stage, 36.8% in aggressive stage . The most frequently used method (in 73.2%) was curretage, irrigation and filling in with bone grafts, in 12.5% of cases block resection and replacement by bone grafts . Total results after all these types of operations evaluated in the interval of 3 years after the operation were very good, i.e . 85.7% remissions, there were 14.3% of recurrence . Of these setbacks 5.4% were in remission for more than 3 years and thus conduced to the increase of the number of remissions to 94.6% which can be evaluated as an excellent result . Local recurrence occurs in 10-15% with the application and 15-25% without the application of local adjuvant therapy . In the third stage in case of extensive destruction we perform resection en bloc, radiotherapy in hardly accessible locations (spine, sacrum, pelvis) . In case of extensive destruction in the region of joints the method of choice is the application of both individual and total replacement.

Infect Immun, 2001 Dec, 69(12), 7437 - 44
Cellular and humoral immune responses to Borrelia burgdorferi antigens in patients with culture-positive early Lyme disease; Vaz A et al.; We determined cellular and humoral immune responses to Borrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects . During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested . During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested . In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB . Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA . The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease . We conclude that cellular and humoral responses to B . burgdorferi antigens are often found among patients with early Lyme disease . In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA.

Obstet Gynecol, 2001 Nov, 98(5 Pt 1), 763 - 70
Labor epidural analgesia and intrapartum maternal hyperthermia; Yancey MK et al.; OBJECTIVE: To determine if women receiving continuous epidural analgesia are more likely to develop intrapartum fever and related neonatal effects . METHODS: We conducted a retrospective cohort analysis of nulliparous women with term gestations in spontaneous labor delivered during a 12-month period immediately before the availability of on-demand labor epidural analgesia (Before group) and a similar group of nulliparas delivered after labor epidural analgesia was available on request (After group) . RESULTS: The frequency of epidural increased from 1% before the availability of on-request epidural analgesia to 83% after epidural analgesia was available on request . A maximal temperature of at least 100.4F was detected in three of 498 (0.6%) women in the Before group, and in 63 of 572 women (11.0%) in the After group (relative risk {RR} = 18.3, 95% confidence interval {CI} 5.8, 57.8, P <.01) . Logistic regression analysis demonstrated that on-request labor epidural analgesia was associated with an intrapartum temperature of at least 99.5F (RR = 3.0, 95% CI 2.3, 3.6, P <.001) and intrapartum temperature of at least 100.4F (RR = 20.2, 95% CI 7.0, 86.0, P <.001) . There were statistically significant increases in the proportion of newborns who had complete blood counts (24% versus 13.5%, RR = 1.5, 95% CI 1.3, 1.8, P <.01) and blood cultures (30.7% versus 8.6%, RR = 1.7, 95% CI 1.2, 2.4, P <.05) in the After period compared with the Before group; however, there was no statistically significant difference in the proportion of infants who received antibiotic therapy for presumed sepsis between the After and Before periods (5.8% versus 4.6%, RR = 1.15, 95% CI 0.8, 1.6, P =.38) . No infants in either group had culture-proven sepsis . CONCLUSION: The use of labor epidural analgesia is associated with a clinically significant increase in the incidence of intrapartum fever.

Trop Med Int Health, 2001 Nov, 6(11), 883 - 90
Modelling parasite drug resistance: lessons for management and control strategies; Hastings IM; Mathematical models of the evolution of drug resistance in infectious diseases are predominantly concentrated in three main areas: antimalarial, antibiotic and anthelmintic resistance . There appears to be little or no cross-reference between them . This literature was examined to identify factors that influence the evolution of drug resistance irrespective of the species and drug under study . The aim is to provide non-technical readers with a basic qualitative understanding of the issues and pitfalls involved in designing drug treatment regimens to minimize the evolution of resistance . The principal factors determining the rate at which resistance evolves appear to be (i) the starting frequency of resistance, (ii) the level and pattern of drug use, (iii) the drug's pharmacokinetic properties, (iv) the number of genes required to encode resistance, (v) the level of sexual recombination in the parasite population, (vi) intrahost dynamics and, in particular, whether 'crowding' effects are present, (vii) the genetic basis of resistance and (viii) the number of individual parasites in an infection . The relative importance of these factors depends on the biology of the organisms under consideration and external factors such as the extent to which the infrastructure of health care delivery constrains the practicalities of drug regimens.

Diabetes Obes Metab, 2001 Oct, 3(5), 332 - 7
Effects of granulocyte-colony stimulating factor in the treatment of diabetic foot infection; Yonem A et al.; AIMS: Foot infections and the subsequent amputation of a lower extremity are the most common cause of hospitalization among patients with diabetes mellitus . Although there are several reasons for susceptibility to infection in diabetic patients, white blood cell dysfunction is considered to be an important cause for this tendency . Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophils from the bone marrow and improves neutrophil functions . Based on this knowledge, the aim of the present study was to investigate the effects of addition of G-CSF to the treatment of foot infections in diabetic patients . METHODS: Thirty diabetic patients with foot infection were included in the study . Fifteen of the patients received standard treatment consisting of local wound care and antibiotics (standard group), and the other 15 patients received G-CSF besides standard treatment (G-CSF group) . The objectives of this study were to determine the time to resolution of infection, time to hospital discharge, need for surgical intervention, and the effects of G-CSF on phagocytosis and respiratory burst of neutrophils . RESULTS: Treatment with G-CSF led to significantly higher neutrophil counts on the 5th and 10th days, and at the end of treatment in the G-CSF treated group compared to the standard group . Respiratory burst of neutrophils increased significantly in both the G-CSF group (from 1.6 +/- 0.3 to 2.3 +/- 0.5, p = 0.001) and the standard group (from 2.0 +/- 0.4 to 2.3 +/- 0.4, p = 0.02) with treatment . But, while phagocytosis of neutrophils increased significantly in the G-CSF group (from 70.4 +/- 2.0 to 74.5 +/- 1.9, p = 0.004), it did not change significantly in the standard group (from 68.1 +/- 0.2 to 69.4 +/- 1.9, p = 0.3) with treatment . Duration of hospitalization (26.9 +/- 2.0 vs . 28.3 days, p < 0.05), duration of parenteral antibiotic administration (22.9 +/- 2.0 vs . 23.3 +/- 1.9 days, p < 0.05), time to resolution of infection (23.6 +/- 1.8 vs . 22.3 +/- 1.7 days, p < 0.05), and need for amputation (13.3% vs . 20%, p > 0.05) were similar between the G-CSF and the standard groups . CONCLUSIONS: Although G-CSF improves neutrophil function as well as increasing the absolute numbers, this improvement is not associated with shortening of duration of antibiotic administration, duration of hospital stay or need for amputation in diabetic foot infection.

J Neurosurg, 2001 Nov, 95(5), 783 - 90
Chiari I malformation: a rare cause of noncommunicating hydrocephalus treated by third ventriculostomy; Decq P et al.; OBJECT: Hydrocephalus associated with Chiari I malformation is a rare entity related to an obstruction in the flow of cerebrospinal fluid (CSF) in the foramen of Magendie . Like all forms of noncommunicating hydrocephalus . it can be treated by endoscopic third ventriculostomy (ETV) . The object of this study is to report a series of five cases of hydrocephalus associated with Chiari I malformation and to evaluate the use of ETV in the treatment of this anomaly . METHODS: Five patients (four women and one man with a mean age of 29.6 years) underwent ETV for hydrocephalus associated with Chiari I malformation between April 1991 and February 1997 . All patients had presented with paroxysmal headaches, which in two cases were associated with visual disorders . All patients had also presented with hydrocephalus (mean transverse diameter of the third ventricle 12.79 mm; mean sagittal diameter of the fourth ventricle 18.27 mm) with a mean herniation of the cerebellar tonsils at 13.75 mm below the basion-opisthion line . Surgery was performed in all patients by using a rigid endoscope . No complications occurred either during or after the procedure, except in one patient who experienced a wound infection that was treated by antibiotic medications . The mean duration of follow up in this study was 50.39 months . Four patients became completely asymptomatic and remained stable throughout the follow-up period . One patient required an additional third ventriculostomy after I year, due to secondary closure, and has remained stable since that time . Postoperative magnetic resonance images demonstrated a significant reduction in the extent of hydrocephalus in all patients (mean transverse diameter of the third ventricle 6.9 mm {p = 0.0035}; mean sagittal diameter of the fourth ventricle 10.32 mm {p = 0.007}), with a mean ascent of the cerebellar tonsils from 13.75 mm below the basion-opisthion line to 7.76 mm below it (p = 0.01) . In addition, CSF flow was identified on either side of the orifice of the third ventriculostomy in all patients postoperatively . CONCLUSIONS: Results in this series confirm the efficacy of ETV in the treatment of hydrocephalus associated with Chiari I malformation . It is a reliable, minimally invasive technique that also provides a better understanding of the pathophysiology of this malformation.

Eur J Dermatol, 2001 Nov-Dec, 11(6), 538 - 44
Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne; Gollnick HP et al.; BACKGROUND/AIMS: The primary aim of the study was to establish the clinical efficacy and safety of a combined treatment consisting of topical 20% azelaic acid (AA) cream and the oral antibiotic minocycline in the therapy of severe inflammatory acne (nodular papulopustular acne and acne conglobata) in a comparison with oral isotretinoin therapy . The secondary aim was to establish the value of AA cream as maintenance therapy in the prevention of recurrent acne . METHODS: This open-label but randomised study involved 85 patients with nodular papulopustular acne or acne conglobata (Leeds grading scale > 4) who were treated for 6 months . In an immediately subsequent 3-month second phase, eligible patients from the initial combination group used the AA cream as maintenance therapy, while the eligible patients from the isotretinoin group served as untreated control . RESULTS: A 6-month course of treatment with topical 20% AA cream plus oral minocycline in 50 patients proved to be effective in nodular forms of acne (median reduction of facial comedones: 70%; of papules and pustules: 88%; of deep inflammatory acne lesions: 100%) . Overall, the combined treatment was not quite as effective as treatment with oral isotretinoin (35 patients; reduction of comedones: 83%; of papules and pustules: 97%; of deep inflammatory acne lesions: 100%) . In the 3-month maintenance therapy phase, about half of the patients who received AA monotherapy maintained the very good facial result achieved by the end of phase I . A similar rate was found in the patients of the isotretinoin group, who received no further active acne treatment . In the other 50% of patients, differences existed between the groups as regards the degree of deterioration: Marked deterioration occurred more frequently under AA treatment, while only slight deterioration was more frequent in the isotretinoin group . The combination was tolerated much better than isotretinoin . The incidence of local side effects observed under the combination of AA and minocycline (36.5%, mainly transient burning and itching of mild or moderate intensity) was considerably lower than that seen with isotretinoin (65.7%) . The rate of local side effects of marked intensity observed under the combination, i.e . 6%, was well within the range of 5-10% previously reported for AA . The incidence of systemic side effects was lower (8%, mainly gastrointestinal symptoms) under the combined therapy than under isotretinoin (14.3%) . CONCLUSION: The combination of topical 20% AA cream and oral minocycline is an highly effective treatment in severe forms of acne . It is better tolerated and associated with fewer risks than oral isotretinoin - in particular, there is no risk of teratogenicity . The combination can be regarded as a valuable alternative in patients for whom isotretinoin is not indicated, who do not wish to use or can not tolerate isotretinoin therapy and particularly in female acne patients of child-bearing potential . Topical 20% AA cream can be used successfully as maintenance therapy to prolong the recurrence-free interval.

J Org Chem, 2001 Nov 16, 66(23), 7729 - 37
Amination reactions of aryl halides with nitrogen-containing reagents mediated by palladium/imidazolium salt systems; Grasa GA et al.; Nucleophilic N-heterocyclic carbenes have been conveniently used as catalyst modifiers in amination reactions involving aryl chlorides, aryl bromides, and aryl iodides with various nitrogen-containing substrates . The scope of a coupling process using a Pd(0) or Pd(II) source and an imidazolium salt in the presence of a base, KO(t)Bu or NaOH, was tested using various substrates . The Pd(2)(dba)(3)/IPr.HCl (1, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) system presents the highest activity with respect to electron-neutral and electron-rich aryl chlorides . The ligand is also effective for the synthesis of benzophenone imines, which can be easily converted to the corresponding primary amines by acid hydrolysis . Less reactive indoles were converted to N-aryl-substituted indoles using as supporting ligand the more donating SIPr.HCl (5, SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene) . The Pd(OAc)(2)/SIPr.HCl/NaOH system is efficient for the N-arylation of diverse indoles with aryl bromides . The general protocol developed has been applied successfully to the synthesis of a key intermediate in the synthesis of an important new antibiotic . Mechanistically, palladium-to-ligand ratio studies strongly support an active species bearing one nucleophilic carbene ligand.

Org Lett, 2001 Nov 15, 3(23), 3675 - 8
An efficient synthesis of (-)-chloramphenicol via asymmetric catalytic aziridination: a comparison of catalysts prepared from triphenylborate and various linear and vaulted biaryls; Loncaric C et al.; {reaction--see text} The antibiotic (-)-choramphenicol has been synthesized in only four steps from p-nitro-benzaldehyde in optically pure form from an asymmetric catalytic aziridination reaction with a chiral catalyst prepared from triphenylborate and the (R)-VAPOL ligand . Catalysts generated from the VAPOL and VANOL ligands give much higher asymmetric induction than do catalysts prepared from 6,6'-diphenylVAPOL, BINOL, and BANOL ligands.

Leuk Lymphoma, 2001 Jul, 42(3), 339 - 46
Outpatient supportive care following chemotherapy for acute myeloblastic leukemia; Allan DS et al.; Treatment of acute myeloid leukemia (AML) involves aggressive myelosuppressive chemotherapy that is generally administered on an inpatient basis . In our centre, AML therapy has been initiated in hospital and followed by early outpatient supportive care according to guidelines established in 1996 . We conducted a review of all patients presenting with AML in our centre between January 1996 and July 1998 to evaluate the safety and feasibility of early outpatient supportive care . Nineteen consecutive patients treated with induction chemotherapy were analyzed . Patients were treated with cytosine arabinoside and an anthracycline as aggressive AML induction therapy with the intent for early discharge . Ten patients (53%) were discharged within 10 days of starting induction chemotherapy (median 4.5 days) . Reasons for remaining in hospital included sepsis, serious medical complications, and social and geographic factors . Patients discharged early had a median of 1.5 readmissions (range 0-3), but had 30% fewer in-hospital days than inpatients (p = 0.03), and 57% fewer days of in-hospital antibiotic therapy (p = 0.01) . There were no significant differences in transfusion requirements or episodes of febrile neutropenia between the two groups . Thirty-one cycles of consolidation therapy were administered to the 18 patients who survived induction . Early discharge from hospital was achieved for 30 cycles (97%) . Nine cycles of consolidation chemotherapy were delivered using outpatient intravenous infusion pumps (29%) . This study supports the feasibility and safety of early discharge and outpatient supportive care following chemotherapy for AML.

Am J Emerg Med, 2001 Nov, 19(7), 535 - 40
ED management of cellulitis: a review of five urban centers; Dong SL et al.; Cellulitis is a common problem presenting to the emergency department (ED) . This study examines the epidemiology of cellulitis in 5 Canadian urban EDs and determines the practice variation in this management among sites . From computerized provincial ED diagnosis information, 10% of cellulitis charts from April 1, 1997 to March 31, 1998 were randomly selected for review . All 5 EDs in one urban region were sampled; physicians were unaware of the study when seeing patients . A standardized audit form was used to collect information pertaining to visits for the incident infection case . Cases were excluded if simple cellulitis was not the primary diagnosis or if procedures such as incision and drainage were initially required . A total of 416 adult charts were retrospectively identified . The mean age was 46 years and 61% were men; 38% had seen another physician before the ED presentation . Cellulitis was most commonly located in the upper (41%) and lower (48%) extremities . Most cases were treated with intravenous cefazolin (58%; range among sites: 49%-66%); however, over 25 different antibiotics and doses were initially prescribed . Each case required a median of 4 (interquartile range {IQR}: 1, 9) ED visits . Some patients (14%) received an increase in dose (3%) or a change in antibiotic regimen (11%) during their treatment . Few patients (3%) required a second change in regimen . Specialist consultations were obtained in only 6% of patients and hospitalization was rare (7%) . The most common discharge prescription was oral cephalexin (62%); however; many different regimens were prescribed . Cellulitis is a common ED problem which consumes considerable resources to treat . Considerable practice variation exists with respect to in-ED and post-ED management . These results suggest the need for the development of practice guidelines for the treatment of this common ED problem.

Bioorg Khim, 2000 Nov, 26(11), 808 - 16
{Chemical synthesis of 15N-labeled zervamicins IIB}; Rimawi WH et al.; Analogues of 16-membered peptide antibiotic zervamicin IIB with the Gln3 and Gln11 residues 15N-labeled at the C alpha-atoms were synthesized by coupling the antibiotic segments (1-4), (5-9), and (10-16) . In turn, these were prepared by a stepwise chain elongation in solution starting from their C-termini using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as an activating agent . The sterically hindered 2-aminoisobutyric acid was introduced by the BOP-dimethylaminopyridine system with the preactivation of the carboxyl component . The segment condensation was performed with the use of the 6-trifluoromethylbenzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate activating reagent . The homogeneity of the resulting zervamicin analogues was confirmed by HPLC, and their structures were proved by NMR spectroscopy and FAB mass spectrometry.

J Am Soc Echocardiogr, 2001 Nov, 14(11), 1139 - 42
Eustachian valve endocarditis: a case series and analysis of the literature; Sawhney N et al.; Eustachian valve endocarditis (EVE) is a syndrome characterized by clinical signs and symptoms of right-sided infective endocarditis in association with an infective vegetation on the eustachian valve . EVE usually occurs without associated involvement of any other cardiac valves, and it is difficult to diagnose accurately by transthoracic echocardiography . Transesophageal echocardiography appears to be a more sensitive tool for the diagnosis of EVE, and it is recommended when a patient with typical signs of right-sided endocarditis has normal results on a transthoracic echocardiography study . In general, EVE responds well to conventional antibiotic therapy.

J Vet Pharmacol Ther, 2001 Oct, 24(5), 303 - 8
Pharmacokinetics of sarafloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications; Ding HZ et al.; Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers) . Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method . Following i.v., i.m . and p.o . doses, the elimination half-lives (t1/2beta) were 3.37 +/- 0.46, 4.66 +/- 1.34, 7.20 +/- 1.92 (pigs) and 2.53 +/- 0.82, 6.81 +/- 2.04, 3.89 +/- 1.19 h (broilers), respectively . After i.m . and p.o . doses, bioavailabilities (F) were 81.8 +/- 9.8 and 42.6 +/- 8.2% (pigs) and 72.1 +/- 8.1 and 59.6 +/- 13.8% (broilers), respectively . Steady-state distribution volumes (Vd(ss)) of 1.92 +/- 0.27 and 3.40 +/- 1.26 L/kg and total body clearances (ClB) of 0.51 +/- 0.03 and 1.20 +/- 0.20 L/kg/h were determined in pigs and broilers, respectively . Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined . Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs . Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 h in pigs, or administered orally every 8 h in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 microg/mL.

Rev Med Interne, 2001 Oct, 22(10), 948 - 58
{Prosthetic valve endocarditis due to Coxiella burnetii: six cases}; Auzary C et al.; PURPOSE: Prosthetic valve endocarditis is a dangerous complication of valvular surgery (3-6%) . Among involved pathogens, Coxiella burnetii is an occasional agent, though isolated with increasing frequency . We report our experience with this peculiar endocarditis and lay stress on specific diagnostic and therapeutic difficulties . METHODS: Between 1990 and 1995, six patients retrospectively met the diagnosis criteria for definite endocarditis due to Coxiella burnetii . RESULTS: Five Algerian men and one French woman presented with prosthetic valve endocarditis with negative blood cultures (on bioprosthesis: four cases, on mechanical valve: two cases) . The main clinical and biological feature was febrile congestive heart failure with hepatomegaly, splenomegaly, hepatic and renal abnormalities, inflammatory syndrome, hypergammaglobulinemia, anemia and lymphopenia . Serological testing for Coxiella burnetii provided diagnosis in all cases . Echocardiography displayed vegetations in all cases . Valvular replacement was performed in four patients . With antibiotic therapy including doxycycline or/and hydroxychloroquine, quinolones or rifampicine, all patients experienced complete clinical, biological and echographic remission . CONCLUSION: Q fever prosthetic valve endocarditis presents as a systemic disorder occurring in patients with valvular heart disease . From now on, early diagnosis and efficient medical treatment may provide permanent prosthetic sterilization.

Clin Infect Dis, 2001 Dec 1, 33(11), 1834 - 41 Epub 2001 Oct 23.
Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974-1998; Katz AR et al.; Leptospirosis is frequently misdiagnosed as a result of its protean and nonspecific presentation . Leptospirosis, a zoonosis with global distribution, commonly occurs in tropical and subtropical regions; most reported cases in the United States occur in Hawaii . All laboratory-confirmed leptospirosis cases in the State of Hawaii from 1974 through 1998 (n=353) were clinically evaluated . The most common presentation involved nonspecific signs or symptoms, including fever, myalgia, and headache . Jaundice occurred in 39% of cases; conjunctival suffusion was described in 28% of these cases . Initiation of antibiotics before the seventh day of symptoms was associated with a significantly shortened duration of illness . Because early recognition and initiation of antibiotic therapy are important, clinicians should familiarize themselves with the clinical presentation of leptospirosis, and when evaluating a patient with a febrile illness, they should obtain exposure and travel histories and entertain the possibility of leptospirosis in the differential diagnosis.

Cancer Res, 2001 Nov 1, 61(21), 7770 - 6
Reversal of mitomycin C resistance by overexpression of bioreductive enzymes in Chinese hamster ovary cells; Baumann RP et al.; The clinical utility of antineoplastic agents is limited by the development of drug resistance by tumors . Mitomycin C (MC) is a bacterial product that must be enzymatically reduced to exert anticancer activity . We have demonstrated that expression of the bacterial MC resistance-associated (MCRA) protein in Chinese hamster ovary (CHO) cells confers profound resistance to this antibiotic under aerobic conditions, but not under hypoxia . MCRA produces resistance to MC by redox cycling of the activated hydroquinone intermediate back to the prodrug form . A CHO cell line developed by stepwise exposure to increasing concentrations of MC likewise expressed high level resistance to MC in air, but not under hypoxia . The overexpression of DT-diaphorase and NADPH:cytochrome c (P-450) reductase, two enzymes known to activate MC, restored sensitivity to MC in both MCRA-transfected and drug-selected cell lines . The level of sensitization was proportional to the quantity of enzyme activity expressed, supporting the concept that the levels of these two activating enzymes are important for sensitivity to MC . The findings of resistance to MC in air but not under hypoxic conditions and of restoration of sensitivity to MC by increasing levels of DT-diaphorase activity, properties not adequately explained by other resistance mechanisms (i.e., decreases in MC activation, repair of DNA lesions, and/or drug efflux), support the hypothesis that a functional mammalian homologue of MCRA may be involved in producing resistance to MC.

Nat Biotechnol, 2001 Nov, 19(11), 1067 - 70
An infectious transfer and expression system for genomic DNA loci in human and mouse cells; Wade-Martins R et al.; The recent completion of the human genome sequence allows genomics research to focus on understanding gene complexity, expression, and regulation . However, the routine-use genomic DNA expression systems required to investigate these phenomena are not well developed . Bacterial artificial chromosomes (BACs) and P1-based artificial chromosomes (PACs) have proved excellent tools for the human genome sequencing projects . We describe a system to rapidly and efficiently deliver and express BAC and PAC library clones in human and mouse cells by converting them into infectious amplicon vectors . We show packaging and intact delivery of genomic inserts of >100 kilobases with efficiencies of up to 100% . To demonstrate that genomic loci transferred in this way are functional, the complete human hypoxanthine phosphoribosyltransferase (HPRT) locus contained within a 115-kilobase BAC insert was shown to be expressed when delivered by infection into both a human HPRT-deficient fibroblast cell line and a mouse primary hepatocyte culture derived from Hprt-/- mice . Efficient gene delivery to primary cells is especially important, as these cells cannot be expanded using antibiotic selection . This work is the first demonstration of infectious delivery and expression of genomic DNA sequences of >100 kilobases, a technique that may prove useful for analyzing gene expression from the human genome.

J Biomol Screen, 2001 Oct, 6(5), 275 - 90
Real experiences of uHTS: a prototypic 1536-well fluorescence anisotropy-based uHTS screen and application of well-level quality control procedures; Turconi S et al.; This paper describes, for the first time, a true ultra-high throughput screen (uHTS) based upon fluorescence anisotropy and performed entirely in 1536-well assay plates . The assay is based upon binding and displacement of a BODIPY-FL-labeled antibiotic to a specific binding site on 70S ribosomes from Escherichia coli (Kd approximately 15 nM) . The screen was performed at uHTS rates (i.e., >100,000 assay wells/24 h) using entirely commercially available equipment . In order to examine the reproducibility of detection of test compound effects, assays were performed in duplicate . Both overall assay statistics and reproducibility for individual compound results were excellent, at least equivalent to conventional HTS assays . Interference artifacts occurred mainly as a result of autofluorescence from test compounds . Well-level quality control procedures were developed to detect, eliminate, or even correct for such effects . Moreover, development of a brighter, longer wavelength probe (based upon Cy3B) markedly reduced such interferences . Overall, the data demonstrate that fluorescence anisotropy-based uHTS is now a practical reality.

Bull Exp Biol Med, 2001 Jul, 132(1), 699 - 704
Relationships between myocardial parenchyma and stroma: regenerative and plastic insufficiency of cardiomyocytes and development of diffuse cardiosclerosis; Nepomnyashchikh LM et al.; Regenerative and plastic myocardial insufficiency characterized by impaired intracellular regeneration, progressive involution and apoptosis of cardiomyocytes associated with selective cardiotoxic effect of anthracycline antibiotic rubomycin is accompanied by enhanced proliferative and functional activities of fibroblasts and other stromal cells . Elimination of 30% cardiomyocytes and their atrophy are accompanied by the development of diffuse myocardial sclerosis, which is considered as a compensatory reaction of the connective tissue to the decrease in the weight of muscle fibers . Remodeling of the myocardium during anthracycline-induced cardiomyopathy due to changes in the parenchyma-stroma relationships does not lead to severe deformation of the heart, which is a favorable factor for normalization of myocardial architectonics after initiation of regenerative processes.

Bull Exp Biol Med, 2001 Jul, 132(1), 637 - 40
NAD and glutathione modulate sensitivity of bone marrow cells to oxidative stress; Egorova AB et al.; We studied in vitro cytostatic effect of doxorubicin on bone marrow cells preincubated with NAD and reduced glutathione . The presence of NAD and glutathione in the medium potentiated membrane toxicity of this antibiotic, but prevented its toxic effects on intracellular pool of pyridine nucleotides during oxidative stress.

Cochrane Database Syst Rev . 2001;(4):CD002900.
Surgical methods for first trimester termination of pregnancy; Kulier R et al.; BACKGROUND: Different surgical methods for termination of pregnancy have evolved over the years: Dilatation and curettage, power operated vacuum aspiration, manual vacuum aspiration (MVA) or hysterotomy . Local or general anaesthesia is used for all methods . Preabortion medical or mechanical cervical preparation may reduce the incidence of cervical or uterine injuries . OBJECTIVES: To compare the safety and efficacy of different surgical methods for first trimester abortion . SEARCH STRATEGY: The Cochrane Controlled Trials Register has been searched . A search of the reference lists of identified trials was performed . An additional MEDLINE search was done using the Internet search service Pub Med . SELECTION CRITERIA: Randomised controlled trials comparing different surgical methods for first trimester abortion were eligible . DATA COLLECTION AND ANALYSIS: Trials under consideration were evaluated for methodological quality and appropriateness for inclusion . Three trials were included, resulting in 2 comparisons: vacuum aspiration versus dilatation and curettage and flexible versus rigid vacuum aspiration cannula . Results are reported as odds ratio for dichotomous data and weighted mean differences for continuous data . MAIN RESULTS: There were no reports of maternal deaths and cases of uterine perforation in the trials identified . Vacuum aspiration versus dilatation and curettage: There were no statistically significant differences for excessive blood loss, blood transfusion, febrile morbidity, incomplete or repeat uterine evacuation procedure, re-hospitalisation, post operative abdominal pain or therapeutic antibiotic use . Duration of operation was statistically significantly shorter with vacuum aspiration compared to D&C in both gestational age subgroups : < 9 weeks: weighted mean difference (WMD) -1.84 minutes, 95% confidence interval (CI) {-2.542,-1.138}; =/> 9 weeks: WMD -0.600 minutes, 95% CI {-1.166,-0.034}) . Flexible versus rigid vacuum aspiration cannula: There were no statistically significant differences with regard to cervical injuries, febrile morbidity, blood transfusion, therapeutic antibiotic use, or incomplete or repeat uterine evacuation procedure . REVIEWER'S CONCLUSIONS: The included studies do not indicate a preference of providers for one or the other method . The trials included are small and lack power to to present meaningful differences for rare outcomes between the groups . outcomes such as women's satisfaction, the need for pain relief or surgeons preference for the instrument have been inadequately addressed . No data outcomes, such as fertility after surgical abortion, are available.

J Anim Physiol Anim Nutr (Berl), 2001 Oct, 85(9-10), 314 - 24
No evidence for active peptide transport in forestomach epithelia of sheep; Martens H et al.; The transport of peptides was studied with isolated preparations of rumen and omasum tissue of sheep by using the conventional Ussing-chamber method and isolated ruminal cells (REC) . Mucosal addition of glycyl-L-glutamine, captopril (angiotensin converting enzyme inhibitor) or cefadroxil (beta-lactam antibiotic) did not change the short-circuit current (I(sc)), or tissue conductance (G(t)) . The intracellular pH, pH(i), in isolated REC was not influenced by the addition of peptides to the buffer solution . These findings do not support the assumption of proton-coupled or electrogenic peptide transport . The determination of unidirectional flux rates of the peptide D-phenylalanyl-L-alanine (2,3-(3)H) showed that the flux rate in the serosal-mucosal direction, J(sm), was greater than J(ms), leading to a small net secretion of peptide . Transport was not significantly inhibited by the serosal addition of ouabain . Enhancing the paracelluIar permeability by an increase of osmotic pressure in the mucosal solution (FREYER and MARTENS, Proc . Soc . Nutr . Physiol . 8, 80, 1999) caused an increase of G(t) and significantly higher transport rates of peptide . The flux rates of peptides (in the nanomolar range) may therefore represent passive and possibly paracellular diffusion and are not of nutritional importance.

Folia Biol (Praha), 2001, 47(5), 171 - 5
Self-initiation of translation of mRNAs devoid of translational initiators in Escherichia coli; Kolev V et al.; Recent studies have shown that the canonical SD-anti-SD interaction is dispensable for the initiation of translation of certain mRNAs in Escherichia coli . In this study the cat and tetR genes were modified to either destroy complementarity to E . coli 16S RNA or completely delete their 5' non-translated regions . Thus a series of cat- and tetR-derived genes were constructed, cloned under a strong constitutive promoter and expressed in E . coli cells . The efficiency of expression was evaluated by the yield of CAT (for the cat gene) and cell viability in increasing concentrations of antibiotic (for both cat and tetR genes) . The obtained results show that the mRNAs transcribed from both series of reporter genes (cat and tetR) were active in vivo . Their activity was preserved even in the cases when the length of their 5' non-translated leader sequences was reduced to one nucleotide for the cat gene and eight nucleotides for the tetR gene . The yield of protein obtained with the latter constructs was detectable and sufficient for bacteria to survive at 50-100 microg/ml chloramphenicol and 20 microg/ml tetracycline, respectively.

Ann Allergy Asthma Immunol, 2001 Oct, 87(4), 335 - 43
Outcome of asthma in children and adolescents at a specialty-based care program; Najada A et al.; BACKGROUND: Asthma remains a major cause of morbidity for children despite national guidelines . OBJECTIVE: To evaluate outcome from a structured specialty-based care program . METHODS: Comparison of previous and subsequent years for children ranging from infancy to adolescence who entered a specialty clinic program at a university hospital serving a widely dispersed patient population . One hundred fifty-seven patients previously receiving primary care for their respiratory symptoms were seen during the study period; 23 were lost to followup, 15 were excluded because of other serious concurrent medical problems, and 119 were available for outcome analysis . Evaluation included historical data base from a structured interview, evaluation of pulmonary physiology, and allergy skin testing . Treatment decisions were evidence-based . Patient and/or family education was targeted at decision-making . Toll-free telephone access to the specialty service was provided around the clock . Frequency of unscheduled medical care, hospitalizations, sleep disturbance, activity interference, attainment of defined criteria for control, and medication use were quantified . RESULTS: Seven hundred thirty-five acute care visits were reduced to 47, and 99 hospitalizations were decreased to 10 (P < 0.001 for both) . Nocturnal symptoms and exercise limitation decreased significantly (P < 0.001 for both) . All criteria for control of asthma were met in 89% of 75 without tobacco smoke exposure and 50% of 44 with exposure (P < 0.0001 for the difference in outcome) . Frequent antibiotic use for respiratory symptoms were eliminated after entering the program . Maintenance medications were not used in 72 with an intermittent pattern of viral respiratory infection-induced asthma . Inhaled corticosteroid use increased from 38 to 68% among 47 subjects with a chronic pattern . CONCLUSIONS: Morbidity from asthma is largely prevented with often less, but better selected, medication than had been occurring in previous primary care . These data have implications for revised guidelines directed at primary care physicians.

Helicobacter, 2001 Sep, 6(3), 249 - 53
A pilot study to determine the effectiveness of garlic oil capsules in the treatment of dyspeptic patients with Helicobacter pylori; McNulty CA et al.; BACKGROUND: Resistance of Helicobacter pylori to clarithromycin and metronidazole is now found worldwide . Steam-distilled garlic oil has in vitro activity against H . pylori and may be a useful alternative treatment strategy . MATERIALS AND METHODS: In this pilot study dyspeptic patients with positive serology for H . pylori confirmed by 13C urea breath test (UBT), at 0 and 2 weeks, were enrolled . Treatment consisted of one 4 mg garlic oil capsule with a meal four times per day for 14 days . H . pylori eradication was defined as a negative UBT at both follow-up appointments . Suppression was defined as a 50% fall in 13C excess between baseline and follow-up 1 . RESULTS: Five patients completed the study . There was no evidence of either eradication or suppression of H . pylori or symptom improvement whilst taking garlic oil . CONCLUSION: These negative results show that, within the gastric milieu, garlic oil at this dose does not inhibit H . pylori . A higher dose administered for a longer time-period may be effective . Antibiotics are usually combined with a proton-pump inhibitor or bismuth salt, as the only antibiotic with any in vivo activity against H . pylori in monotherapy is clarithromycin . A proton pump inhibitor raises gastric pH and, by increasing bacterial division, may increase the in vivo activity of garlic oil . This may be worth pursuing in a future trial.

Mol Genet Genomics, 2001 Oct, 266(2), 276 - 88
The entire nogalamycin biosynthetic gene cluster of Streptomyces nogalater: characterization of a 20-kb DNA region and generation of hybrid structures; Torkkell S et al.; Fragments spanning 20 kb of Streptomyces nogalater genomic DNA were characterized to elucidate the molecular genetic basis of the biosynthetic pathway of the anthracycline antibiotic nogalamycin . Structural analysis of the products obtained by expression of the fragments in S . galilaeus and S . peucetius mutants producing aclacinomycin and daunomycin metabolites, respectively, revealed hybrid compounds in which either the aglycone or the sugar moiety was modified . Subsequent sequence analysis revealed twenty ORFs involved in nogalamycin biosynthesis, of which eleven could be assigned to the deoxysugar pathway, four to aglycone biosynthesis, while the remaining five express products with unknown function . On the basis of sequence similarity and experimental data, the functions of the products of the newly discovered genes were determined . The results suggest that the entire biosynthetic gene cluster for nogalamycin is now known . Furthermore, the compounds obtained by heterologous expression of the genes show that it is possible to use the genes in combinatorial biosynthesis to create novel chemical structures for drug screening purposes.

Herz, 2001 Sep, 26(6), 391 - 7
{Management of imminent emboli in endocarditis: are they predictable?}; Mugge A; BACKGROUND: Patients with infective endocarditis are at risk for embolic complications . Emboli often occur very early in the course of endocarditis . VEGETATIONS: Pathologic substrate of emboli are vegetations which can be visualized by echocardiography with high sensitivity and accuracy . The question whether echocardiographically derived characteristics of vegetations such as size, mobility, location, and "consistency" poses an increased risk for complications, in particular arterial embolism, remains controversial . An analysis of pooled studies revealed an odds ratio of 2-3 for increased risk of embolization in the presence of a vegetation > 10 mm, particularly in mitral valve endocarditis . TREATMENT AND PREVENTION: However, because of poorly defined co-variables, lack of standardized methods for measurements, as well as a high overlap in the vegetation size between patients with and without embolic complications, no therapeutic implications can be drawn on the echocardiographic findings alone . It appears that an early diagnosis with initiation of an adequate antibiotic therapy is still the best prevention for embolic complications.

J Econ Entomol, 2001 Oct, 94(5), 1260 - 7
Resistant potato selections contain leptine and inhibit development of the Colorado potato beetle (Coleoptera: Chrysomelidae); Lorenzen JH et al.; We recently described a new source of host-plant resistance to the Colorado potato beetle, Leptinotarsa decemlineata (Say), in a tetraploid potato (Solanum tuberosum L.) selection, ND2858-1 . This genotype, and selected backcross progeny, had little damage while check cultivars were defoliated in open-choice field assays . To further characterize the observed deterrence, we determined foliar glycoalkaloids and conducted no-choice assays with ND2858-1 backcross progeny genotypes (ND4382-n) . Development of neonate L . decemlineata in detached leaf assays on resistant progeny genotypes was delayed and larval weight gain after 4 d was inhibited by 75% relative to larval development and weight gain on susceptible genotypes . Inhibition of larval development in detached leaf assays with the selected progeny genotypes was equivalent to that of high-leptine genotypes of S . chacoense Bitter . Foliar glycoalkaloids of resistant genotypes included low levels of leptines I and II . The unlikely nature of this cross and the presence of leptine in this and resistant progeny selections cast doubt on the recorded pedigree . Molecular analyses were conducted by restriction fragment-length polymorphism and amplified fragment-length polymorphisms . Both methods established a high degree of relatedness to S . tuberososum and S . chacoense but not to S . fendleri . We conclude that ND2858-1 did not originate from a cross with S . fendleri, but is likely derived from S . chacoense . Oviposition and larval survival were reduced when adult L . decemlineata were placed in cages with resistant genotypes; an effect that was enhanced by inclusion of Perillus bioculatus F . Therefore, the nonpreference previously observed in open-choice field defoliation assays is also associated with antibiotic effects on L . decemlineata . The resistance may be caused by leptines, but is greater than would be expected by the leptine content . This source of host plant resistance could be a cost-effective management strategy, especially if combined with other resistance mechanisms or compatible control measures to delay development of resistance in the target insects.

Med Parazitol (Mosk), 2001 Jul-Sep, (3), 3 - 11
{Borreliae as possible antagonists of tick-borne encephalitis virus: parasitologic and clinical aspects}; Alekseev AN et al.; An attempt was made to compare the Borrelia-TBE-virus interface in Ixodes ticks and in patients . The authors suppose that Borrelia might suppress viral replication in ticks and in TBE-susceptible individuals . Whether antibiotics (particularly representatives of the tetracycline group) may be essential in treating tick-borne diseases is also discussed . Examples of antibiotic suppression of Borrelia that made the clinic presentation of encephalitis more severe as a consequence are analyzed and discussed . The calculated risk for borreliosis or tick-borne encephalitis and the actual morbidity rates were compared . Possible reasons for disagreement in the results are also discussed.

Med Wieku Rozwoj, 2001 Apr-Jun, 5(2), 141 - 7
{Pharmacokinetic and therapeutic monitoring of gentamicin serum concentration in neonates}; Kaminska E et al.; Pharmacokinetic analysis of gentamicin in 355 neonates hospitalized in the Clinical Dept . of Neonatology of the National Institute of Mother and Child in Warsaw was performed . The patients' group consisted of 119 premature and 236 full-term neonates, who were receiving gentamicin i.v . in the mean doses 4.461 +/- 0.921 ing/kg and 4.706 +/- 0.676 mg/kg, respectively . With use of the non-compartmental method, the following pharmacokinetic parameters were measured: biological half-life (t 0.5), elimination rate constant (k el), area under the curve (AUC), volume of distribution (V d) and total clearance (C T) . Results differ considerably in term and preterm neonates and amount to: 11.25+/- 3.40 h-1, 0.0673 +/- 0.02 h-1, 233.7+/- 95.44 ug h/ml, 1.22 +/- 0.79 l/kg, 0.086 +/- 0.077 l/h/kg - for premature neonates versus 8.19 +/- 2.58 h, 0.089 +/- 0.02 h-1, 157.5 +/- 60.2 ug h/ml, 0.637 +/- 0.316 l/kg, 0.060 +/- 0.042 l/h/kg for full- term neonates . The analysis of pharmacokinetic parameters suggests that these findings may be already used as a preliminary basis of gentamicin population pharmacokinetics in both groups of neonates . The obtained results confirm that monitoring of gentamicin serum concentration helps to improve the treatment of neonates with this antibiotic . It was also found that the use of the dosing schedule of gentamicin with the dose intervals 36 or 48 h should guarantee adequate Cmax and Cmin without the need of routine monitoring of each patient in the premature neonate group.

Appl Environ Microbiol, 2001 Nov, 67(11), 5055 - 62
Peptide synthetase gene in Trichoderma virens; Wilhite SE et al.; Trichoderma virens (synonym, Gliocladium virens), a deuteromycete fungus, suppresses soilborne plant diseases caused by a number of fungi and is used as a biocontrol agent . Several traits that may contribute to the antagonistic interactions of T . virens with disease-causing fungi involve the production of peptide metabolites (e.g., the antibiotic gliotoxin and siderophores used for iron acquisition) . We cloned a 5,056-bp partial cDNA encoding a putative peptide synthetase (Psy1) from T . virens using conserved motifs found within the adenylate domain of peptide synthetases . Sequence similarities with conserved motifs of the adenylation domain, acyl transfer, and two condensation domains support identification of the Psy1 gene as a gene that encodes a peptide synthetase . Disruption of the native Psy1 gene through gene replacement was used to identify the function of this gene . Psy1 disruptants produced normal amounts of gliotoxin but grew poorly under low-iron conditions, suggesting that Psy1 plays a role in siderophore production . Psy1 disruptants cannot produce the major T . virens siderophore dimerum acid, a dipetide of acylated N(delta)-hydroxyornithine . Biocontrol activity against damping-off diseases caused by Pythium ultimum and Rhizoctonia solani was not reduced by the Psy1 disruption, suggesting that iron competition through dimerum acid production does not contribute significantly to disease suppression activity under the conditions used.

Respir Care, 2001 Nov, 46(11), 1294 - 303
Chronic obstructive pulmonary disease management: the evidence base; MacIntyre NR; In long-term management of stable chronic obstructive pulmonary disease (COPD), a number of medications improve pulmonary function test results . The long-term clinical benefits of those drugs would seem intuitive, but there is very little strong evidence that long-term outcomes in COPD are substantially affected by those drugs . Nevertheless, symptom improvement such as dyspnea reduction is certainly strong reason to use those agents . The 2 most compelling bodies of evidence in stable COPD are for oxygen therapy in the chronically hypoxemic patient and pulmonary rehabilitation to improve exercise tolerance and dyspnea . Inhaled corticosteroids also appear to be useful in patients at risk for frequent exacerbations . In acute exacerbations, the rationale for therapy comes in part from the large body of literature regarding acute asthma therapy . Bronchodilator therapy and corticosteroids both seem to reduce the severity and the duration of exacerbations . Moreover, routine antibiotic use seems beneficial, and the role of noninvasive positive-pressure ventilation with patients suffering impending respiratory failure from acute COPD exacerbations is well supported by the literature.

Hepatogastroenterology, 2001 Sep-Oct, 48(41), 1375 - 8
Esophagopericardial fistula attributed to a barogenic rupture of the esophagus . Report of a case and review of the literature; Gonzalez-Ojeda A et al.; In this case we describe a fatal condition of esophagopericardial fistula secondary to barogenic rupture of the esophagus . The review of the literature disclosed only one fatal case (reported in 1968) of esophagopericardial fistula attributed to barogenic rupture of the esophagus . Early diagnosis and adequate treatment including pericardiocentesis along with intermittent drainage of the pericardium, full-course antibiotic therapy and a timely, well-planned surgical intervention will substantially improve the prognosis in this type of pathology . Patients similar to our case should be treated with either surgical bipolar esophageal exclusion (conservative disconnection) or esophagectomy combined with large drainage of the pericardial and mediastinal spaces . This case report reinforces the complexity of the diagnosis, and perhaps the need for clinical awareness and the inclusion of this entity in a differential diagnosis.

Radiol Med (Torino), 2001 Sep, 102(3), 154 - 8
{Percutaneous implant of Denver peritoneovenous shunt: a new opportunity for the interventional radiologist}; Spreafico C et al.; PURPOSE: The study is aimed at presenting our experience in the implant of Denver peritoneovenous shunts . Medical treatment-resistant ascites, either neoplastic or related to hepatic failure, is highly symptomatic and its treatment is indicated in order to improve patients' quality of life . One of the most efficient methods of treatment consists in implanting a peritoneovenous shunt . The availability of this device and its percutaneous implantation provide Interventional Radiologists with the possibility of expanding their repertoire . MATERIAL AND METHODS: Thirteen shunts were implanted in 12 patients, 10 with neoplastic ascites and 2 with hepatic failure-related ascites . In 1 patient a second device had to be implanted . All the procedures were performed in the Interventional Radiology Department, under local anesthesia and mild sedation . The central venous access was by the subclavian vein in 7 cases and the internal jugular vein in 6 cases . The puncture kit is consists of 2 needles, 1 for venous puncture and 1 for peritoneal puncture, 2 angiographic J-guide wires, 2 peel-away introducers, and a chamber containing the double valve-pump connected with both the venous and the peritoneal catheters . The whole device is placed subcutaneously thus allowing fluids to flow from the peritoneum to the vein either spontaneously, if intra-abdominal pressure exceeds 3cm of water, or by manual compression exerted on the pump itself . RESULTS: All implants were successfully performed . One transient complication occurred consisting in a mild inflammatory reaction along the subcutaneous catheter route, which promptly solved by antibiotic therapy . So far a total of 1773 catheter/days have been accumulated . 7/10 of the neoplastic patients died from progressive disease after 915 catheter/days (median 120, range 30-180) . In a cirrhotic patient the first shunt occluded after 430 days due to hemoperitoneum caused by hepatic biopsy: it was removed and a new one implanted . Five shunts are in now use, with a follow-up of 30, 48, 70, 120 and 160 days each . DISCUSSION: The implanting technique was well tolerated by all patients and it could be performed under local anesthesia . The central vein puncture was easy for both accesses but the introducer diameter (12F) and the possibility of clavicle pinch-off induced us to use the internal jugular approach in the last six cases, which provided a reduced risk of pneumothorax and a better catheter track . In the patients with neoplastic ascites we observed neither disease dissemination nor changes in the patients' changed related to the shunt . Our results show that the implant of Denver venous-peritoneal shunts is a relatively easy procedure, which can be performed by Interventional Radiologists on a regular basis.

Gastroenterology, 2001 Nov, 121(5), 1120 - 6
Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease; Moayyedi P et al.; BACKGROUND & AIMS: Observational studies have suggested that Helicobacter pylori may protect against gastrointestinal reflux disease (GERD), but these results could be due to bias or confounding factors . We addressed this in a prospective, double blind, randomized, controlled trial . METHODS: H . pylori-positive patients with at least a 1-year history of heartburn with a normal endoscopy or grade A esophagitis were recruited . Patients were randomized to 20 mg omeprazole, 250 mg clarithromycin, and 500 mg tinidazole twice a day for 1 week or 20 mg omeprazole twice a day and identical placebos . A second concurrently recruited control group of H . pylori-negative patients were given open label 20 mg omeprazole twice a day for 1 week . All patients received 20 mg omeprazole twice a day for the following 3 weeks and 20 mg omeprazole once daily for a further 4 weeks . Omeprazole was discontinued at 8 weeks and patients were followed up for a further 10 months . A relapse was defined as moderate or severe reflux symptoms . H . pylori eradication was determined by 13C-urea breath test . RESULTS: The H . pylori-positive cases were randomized to antibiotics (n = 93) or placebo (n = 97) . Relapse of GERD occurred in 83% of each of the antibiotic, placebo, and H . pylori-negative groups during the 12-month study period . Life tables revealed no statistical difference between the 2 H . pylori-positive groups (log rank test, P = 0.84) or between the 3 groups (log rank test, P = 0.94) in the time to first relapse . Two patients in each group developed grade B esophagitis at 12 months . CONCLUSIONS: H . pylori eradication therapy does not seem to influence relapse rates in GERD patients.

Scott Med J . 2001 Aug;46(4):114.
Progressive pneumonia complicating steroid-dependent asthma; Hart SP et al.; We describe a patient who developed pulmonary nocardiosis whilst taking long term oral steroids for asthma . Nocardiosis is more common than is generally appreciated by clinicians, is notoriously difficult to diagnose, and is associated with significant mortality . This patient developed progressive pneumonia despite antibiotic therapy, which is typical of pulmonary nocardiosis . It is important to consider this treatable condition in the differential diagnosis of pneumonia.

J Clin Epidemiol, 2001 Nov, 54(11), 1103 - 11
The case for comprehensive quality indicator reliability assessment; Scinto JD et al.; To demonstrate the importance of evaluating overall quality indicator reliability, in addition to component or variable level reliability, a comparison of interrater agreement on four chart-abstracted pneumonia-related processes of care was conducted . The hospital medical records of 356 Medicare patients' recent discharges for pneumonia were independently abstracted by different abstractors . Kappa, prevalence and bias-adjusted kappa, P(pos), P(neg), and the Bias Index were used to assess reliability of composite quality indicators and their components . The adjusted kappas for the data elements used to determine eligibility to receive as well as to derive the pneumonia-related processes of care ranged from 0.68 to 1.0 . The adjusted kappa associated with overall eligibility to receive the pneumonia-related processes of care was 0.63 . The kappa statistics for determining if processes of care were provided ranged from 0.56 to 0.83 and increased to 0.65 and 0.85 upon adjustment for the prevalence effect . Kappas for the composite quality indicators were lower, but improved with adjustment for the prevalence effect . The composite quality indicator with the highest adjusted kappa value was oxygenation assessment (0.93); the composite quality indicator with the lowest adjusted kappa value was antibiotic administration within 8 hours of hospital arrival (0.74) . This study establishes the reliability of pneumonia indicators and underscores the need for reliability assessment at the quality indicator level, as well as at the component level.

J Org Chem, 1999 Jan 8, 64(1), 23 - 27
Total Synthesis of Myxalamide A; Mapp AK et al.; The polyene antibiotic myxalamide A (1) has been prepared by total synthesis . The synthesis illustrates a useful strategy for synthesis in which the high 1,2-stereocontrol achievable with the aldol reaction can be parlayed by other stereoselective processes so as to give compounds having two or more stereocenters with remote relationships . Application of the Evans asymmetric aldol reaction to aldehyde 13 gives the beta-hydroxy imide 17 . Because the substrate is an alpha,beta-unsaturated aldehyde, the alcohol is allylic . After suitable functional group manipulation, this allylic alcohol is subjected to enolate Claisen rearrangement (as propionate 22) to give allylsulfide 23, having three stereocenters with a 1,4,5-relationship . Further functional group manipulation and one-carbon homologation converts this intermediate into 26, which is oxidized and subjected to Evans-Mislow allylsulfoxide rearrangement to obtain 27, having three stereocenters with a 1,2,5-relationship . The synthesis of myxalamide A was completed by converting aldehyde 30 into dienyne 40 . Alkyne 40 was hydroborated with catechol borane, and the resulting E-vinylborane was subjected to Suzuki coupling with the Z-iodo triene 9 to provide myxalamide A (1).

Pediatr Emerg Care, 2001 Oct, 17(5), 358 - 60
Pediatric eye injury due to Avena fatua (wild oats); Taylor C et al.; OBJECTIVE: We report on florid and unusual ophthalmic physical signs in three children where the trauma was caused by seeds from Avena fatua, a grass common in western North America . DESIGN: Case series and literature review . SETTING: Three local emergency departments (ED) during the fall of 1998 . PATIENTS OR PARTICIPANTS: Three children reporting to an ED with an acutely painful eye from which the foreign body was identified botanically as Avena fatua . INTERVENTIONS: None . MAIN OUTCOME MEASURES: Symptoms, interventions, duration of problem . RESULTS: Three male children (6, 10, 14 years) presented separately following incidents in which they had sustained direct eye injury . Each child immediately experienced severe pain and profuse watering of the eye . Severe localized edema of the conjunctiva and inflammation was evident with conjunctival vessel injection leading to bleeding, reminiscent of a chemical "burn." Initially, two children appeared to have an eyelash caught behind the lower lid . In both instances, the emergency physicians initially dismissed the possibility of there being a significant foreign body, but because of the severity of the pain, conjunctival vessel injection, and edema, they attempted to remove the "lash." Removal of the foreign body proved difficult in all three cases, requiring far greater traction than anticipated . Intact seedpods had become embedded in the subconjunctival space . Ophthalmic analgesia relieved the pain immediately, but in one child who was treated with topical antibiotic alone, significant pain was experienced for 18 hours, until steroid-antibiotic therapy was instituted . All injuries occurred in late summer when the grass propagates . CONCLUSIONS: The physical signs of scleral vasculitis and conjunctival edema can be mistaken for chemical injury or allergic chemosis, but where a foreign body resembling a hair or eyelash is visible, the presence of a seed-pod retained in the subconjunctival space must be considered, particularly if the patient reports exposure to wild grass . Application of local analgesia, foreign body removal, and steroid-antibiotic treatment is recommended.

Am J Respir Crit Care Med, 2001 Oct 1, 164(7), 1182 - 5
Polymyositis-dermatomyositis-associated interstitial lung disease; Douglas WW et al.; We report findings in 70 patients with both diffuse interstitial lung disease and either polymyositis (PM) or dermatomyositis (DM) . Initial presentations were most commonly either musculoskeletal (arthralgias, myalgias, and weakness) or pulmonary (cough, dyspnea, and fever) symptoms alone; in only 15 patients (21.4%) did both occur simultaneously . Pulmonary disease usually took the form of acute to subacute antibiotic-resistant community-acquired pneumonia . Chest radiographs and computed tomography most commonly demonstrated bilateral irregular linear opacities involving the lung bases; occasionally consolidation was present . Jo-1 antibody was present in 19 (38%) of 50 patients tested . Synchronous associated malignancy was present in 4 of 70 patients (5.7%) . Surgical lung biopsies disclosed nonspecific interstitial pneumonia (NSIP) in 18 of 22 patients (81.8%), organizing diffuse alveolar damage (DAD) in 2, bronchiolitis obliterans organizing pneumonia (BOOP) in 1, and usual interstitial pneumonia (UIP) in 1 . Treatment usually included prednisone in 40-60 mg/d dosages for initial control, followed by lower dose prednisone plus an immunosuppressive agent such as azathioprine or methotrexate for disease suppression . Survival was significantly better than that observed for historical control subjects with idiopathic UIP, and was more consistent with survival previously reported in idiopathic NSIP . There was no difference in survival between Jo-1 positive and Jo-1 negative groups.

Ann Trop Med Parasitol, 2001 Sep, 95(6), 587 - 93
Risk factors for toxoplasmic encephalitis in HIV-infected patients: a case-control study in Brazil; Nascimento LV et al.; A case-control study to identify the risk factors for toxoplasmic encephalitis (TE) among HIV-infected patients with latent Toxoplasma gondii infection was performed in a teaching hospital in south-eastern Brazil . Although the subjects were all positive for serum IgG antibodies to Toxoplasma, some (the cases) developed TE during routine follow-up at the hospital whereas others (the controls) did not . Adjusted odds ratios (aOR) were estimated by multiple logistic regression after controlling for potential confounders . Only 46 (22%) of the 210 cases but 93 (45%) of the 205 controls were on prophylactic regimens with co-trimoxazole {aOR = 0.30; 95% confidence interval (CI) = 0.15-0.60} . Subjects with fewer than 100 (aOR = 37.09; CI =7.49-183.67) or between 100 and 200 CD4 cells/microl (aOR = 10.20; CI =2.00-51.90) were at substantially increased risk of developing TE than those with >400 CD4 cells/microl . Although the results of preliminary, unadjusted data analysis indicated that male sex and homosexual or bisexual activity might be additional risk factors, these associations were not found to be statistically significant by multiple regression analysis . In conclusion, no risk factors for TE other than low CD4 cell counts and failure to receive prophylaxis were found among HIV-infected Brazilian patients with past exposure to Toxoplasma . Seropositive patients with CD4 cell counts above 100/microl (the point at which specific prophylaxis is usually recommended) but below 200/microl might also benefit from effective anti-TE prophylaxis.

J Org Chem, 1997 May 16, 62(10), 3271 - 3284
Total Synthesis of Bafilomycin A(1); Toshima K et al.; The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A(1) (1), the first specific potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and beta-hydroxyl hemiacetal side-chain subunits . The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization . The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A(1) . The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.

J Org Chem, 1997 Jan 24, 62(2), 320 - 324
Kinamycin Biosynthesis . Synthesis, Isolation, and Incorporation of Stealthin C, an Aminobenzo{b}fluorene; Gould SJ et al.; A new intermediate in the biosynthesis of the benzo{b}fluorene antibiotic, kinamycin D, has been identified . 11-Amino-4,5,9-trihydroxy-2-methyl-10H-benzo{b}fluoren-10-one was synthesized and shown to be present in extracts of Streptomyces murayamaensisfermentations . A deuterated sample was prepared and shown to be specifically incorporated into kinamycin D . This new intermediate, now named stealthin C, is also the probable hydroxylation substrate for the biosynthesis of stealthin A by S . viridochromogenes.

J Vasc Surg, 2001 Oct, 34(4), 616 - 22
Long-term results of cryopreserved arterial allograft reconstruction in infected prosthetic grafts and mycotic aneurysms of the abdominal aorta; Leseche G et al.; PURPOSE: This prospective, observational study determined the long-term outcome in patients with abdominal aortic infection (primary or prosthetic graft) who were treated with simultaneous aortic/graft excision and cryopreserved arterial allograft reconstruction . METHODS: From April 1992 to March 2000, patients with abdominal aortic infection underwent complete or partial excision of the infected aorta/prosthetic graft and cryopreserved arterial allograft reconstruction . Arterial allografts were harvested from multiple organ donors and cryopreserved at -80 degrees C without rate-controlled freezing . The patients were observed for survival, limb salvage, persistence and/or recurrence of infection, and allograft patency . The results were calculated with life-table methods . RESULTS: During the 8-year study period, 28 consecutive patients (27 men, 1 woman; mean age, 64 years) underwent treatment for abdominal aortic infection (23 graft infections, including 7 graft-enteric fistulas and 5 primary aortic infections) . Allograft reconstruction was performed as an emergency procedure in 13 patients (46%) . The mean follow-up period was 35.4 months (range, 6-101 months) . The overall treatment-related mortality rate was 17.8% (17% for graft infection, 20% for primary aortic infection) . The overall 3-year survival was 67% . There was no early or late amputation . There was no persistent or recurrent infection, and none of the patients received long-term (> 3 months) antibiotic therapy . Reoperation for allograft revision, excision, or replacement was necessary in four patients (17%) who were available for examination, with no reoperative perioperative death . The 3-year primary and secondary allograft patency rates were 81% and 96%, respectively . CONCLUSION: Our experience with cryopreserved arterial allograft in the management of abdominal aortic infection suggests that this technique seems to be a useful option for treating one of the most dreaded vascular complications.

J Org Chem, 1996 Sep 20, 61(19), 6517 - 6522
Total Synthesis of (-)-Muscoride A; Wipf P et al.; The recently isolated cyanobacterium metabolite muscoride A was synthesized in 15 steps and in 4.3% overall yield . Novel structural features of this peptide antibiotic include the presence of a threonine-derived bioxazole core and an N-(1,1-dimethyl)allyl ("reverse prenyl") valine residue . In the context of our synthesis, efficient new strategies for the preparation of these segments were developed . The synthesis of two epimers of muscoride A allowed the unambiguous assignment of the relative and absolute configuration of the natural product by NMR and optical rotation analyses.

J Org Chem, 1996 Sep 6, 61(18), 6175 - 6182
Total Synthesis of (+)-Sinefungin; Ghosh AK et al.; Sinefungin (1) a nucleoside antibiotic isolated from Streptomyces has been synthesized from D-ribose . Both the C-6 and C-9 stereogenic centers were constructed by efficient asymmetric syntheses . The C-6 amine stereochemistry was set by a highly diastereoselective allylation (>99% de) of a (1S,2R)-1-amino-2-indanol-derived oxazolidinone 9 followed by a Curtius rearrangement of 11 to 12 . The C-9 amino acid stereochemistry of sinefungin (1) was established by a rhodium chiral bisphosphine-catalyzed asymmetric hydrogenation of an alpha-(acylamino)acrylate derivative . The anomeric adenosylation of the mixture of anomeric acetates 20 in the presence of C-6 urethane NH was found to be extremely difficult . Conversion of the C-6 urethane NH as its N-benzyl derivative 21 was necessary prior to the adenosylation reaction . Successful adenosylation was effectively carried out by Vorbruggen's protocol utilizing persilylated N(6)-benzoyladenine and trimethylsilyl triflate.

J Org Chem, 1996 Jul 12, 61(14), 4623 - 4633
Total Synthesis of Dimethyl Sulfomycinamate; Kelly TR et al.; Dimethyl sulfomycinamate (1), a methanolysis product from the natural antibiotic sulfomycin I, is synthesized in 11 steps (Scheme 19) . The chemistry of various pyridine, thiazole, and oxazole heterocycles and their coupling reactions under palladium catalysis are examined . The key transformations in the synthesis are the selective palladium-catalyzed coupling reactions on doubly activated pyridine 62 and the condensation reaction between bromo ketone 69 and amide 28 to form the oxazole moiety 76 . The first preparation of oxazole triflates is described, as are some of their chemical properties.

J Org Chem, 1996 Mar 8, 61(5), 1756 - 1760
Phosphinate Inhibitors of the D-Glutamic Acid-Adding Enzyme of Peptidoglycan Biosynthesis; Tanner ME et al.; We report the synthesis and initial evaluation of the first effective inhibitors of the D-glutamic acid-adding enzyme (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase or MurD) . This enzyme plays a key role in bacterial peptidoglycan biosynthesis and is therefore a target for antibiotic design . Phosphinic acid 3 is a dipeptide analog linked to uridine diphosphate by a hydrophobic spacer . It is a good inhibitor of the enzyme (IC(50) = 0.68 &mgr;M) as it closely resembles the tetrahedral intermediate that is presumed to form in the ligation reaction . Compound 4 lacks the terminal UMP group, and compound 5 lacks both the linker and UDP functionalities . These are less effective inhibitors of the enzyme with IC(50) values of 29 &mgr;M and >1 mM, respectively . Preincubation of the enzyme in the presence of inhibitor 3 and ATP does not result in irreversible inhibition or in the formation of a slowly decomplexing species, suggesting that the phosphinic acid is not phosphorylated in the active site.

J Org Chem, 1996 Mar 8, 61(5), 1673 - 1676
First Synthesis of Caerulomycin C; Trecourt F et al.; The first synthesis of caerulomycin C (1), an antibiotic produced by Streptomyces caeruleus, is reported . This molecule, which exhibits a 2,3,4,6-tetrasubstituted pyridine structure, was prepared from 3,4-dimethoxypyridine in a five-step sequence . The methodology involves metalation, transmetalation, aromatic cross-coupling, and halogen migration reactions.

Monaldi Arch Chest Dis, 2001 Jun, 56(3), 240 - 7
Cystic fibrosis: review of the decade; Jaffe A et al.; The median estimated life expectancy of children with cystic fibrosis (CF) born in 1990 is 40 years which represents a doubling in the last 20 years, and nearly half of all patients are now adults . Since the identification of the gene, more than 1000 gene mutations have been discovered . This gene encodes for the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that is thought to have a role in ion transport, mucus rheology, inflammation and bacterial adherence . Various therapeutic mechanisms are currently being investigated in an attempt to overcome these abnormalities . Recombinant human DNase is beneficial in many patients and the use of anti-inflammatory agents such as steroids, ibuprofen and macrolides have potential . Despite these advances in treatment it is essential that these patients are diagnosed early . Whilst the case for neonatal screening is not absolutely conclusive the evidence is highly suggestive that it would be beneficial . It may be that, in the future, new treatments such as gene therapy will be more effective in those patients who have not yet developed lung disease . Whilst gene therapy and other new treatments such as bilateral living lobar lung donation give our patients optimism for the future it is important to remember that the increase in survival is a result of good physiotherapy, nutrition, aggressive antibiotic use and an increase in our understanding of the disease . It is important that patients continue to be referred early to tertiary CF centres.

Issues Law Med, 1986 Nov, 2(3), 241 - 52
Order in the Steinhaus case; Minnesota . County Court et al.; KIE: In April 1986, one-month-old Lance Tyler Steinhaus sustained serious injuries, attributed to abuse by his father, that left him comatose . His mother and his physicians agreed that he should not be treated aggressively . The Redwood County (Minnesota) Welfare Department obtained a temporary order restraining withdrawal of Lance's antibiotic therapy . Lance's mother and Dr . David Steinhorn, a pediatrician, appealed to the County Court to dissolve the temporary injunction . Judge George I . Harrelson in this decision denied their request on the grounds that both state and federal law establish that infants with life-threatening conditions have a right to medically-indicated treatment and that Lance Steinhaus had such a right because he was in a "vegetative state" rather than technically "comatose." {Editor's note: After conducting another hearing on Lance's neurological status, the court ruled on 18 October that Lance was irreversibly comatose and ordered only "comfort care."}

Clin Infect Dis, 2001 Nov 15, 33(10), 1687 - 91 Epub 2001 Oct 12.
Isoniazid preventive therapy, hepatitis C virus infection, and hepatotoxicity among injection drug users infected with Mycobacterium tuberculosis; Sadaphal P et al.; Treatment of latent Mycobacterium tuberculosis infection with isoniazid can cause hepatotoxicity, but the risk of isoniazid-associated hepatotoxicity among persons coinfected with hepatitis C virus (HCV) is unknown . We conducted a prospective study among 146 injection drug users with M . tuberculosis infection and normal baseline hepatic transaminase values who were treated with isoniazid . Of 146 participants, 138 (95%) were HCV-seropositive . Thirty-seven participants (25%) were human immunodeficiency virus (HIV)-seropositive . Thirty-two (22%; 95% confidence interval {CI}, 16%-30%) of 146 participants developed transaminase value elevations to >3 times the upper limit of normal . Transaminase value elevation was associated with concurrent alcohol use but not with race, age, presence of hepatitis B surface antigen, HIV-1 infection, or current injection drug use . Isoniazid was withdrawn from 11 participants (8%; 95% CI, 4%-13%) . Of 8 deaths during follow-up, none were attributed to isoniazid-associated hepatotoxicity . The risk of transaminase value elevation and drug discontinuation for HCV-infected persons receiving isoniazid was within the range reported for populations with lower HCV prevalence.

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