Surg Neurol, 2002 Sep-Oct, 58(3-4), 266 - 70 Cerebellar abscesses secondary to occipital dermoid cyst with dermal sinus: case report; Akhaddar A et al.; BACKGROUND: Hydrocephalus and cerebellar abscesses as the principal manifestations of posterior fossa dermoid cyst are rare . In addition, extradural dermoid cyst of the posterior fossa has been described in only 9 cases in the literature . We present an unusual case of obstructive hydrocephalus due to cerebellar abscesses induced by an adjacent extradural dermoid cyst with complete occipital dermal sinus . CASE DESCRIPTION: A 14-month-old child presented with acute raised intracranially pressure, seizures, and meningitis . Neuroradiological studies revealed cerebellar cysts with ring enhancement associated with a contiguous occipital cyst, with compression of the adjacent cisterns and the fourth ventricle causing hydrocephalus . The diagnosis of cerebellar abscesses with congenital occipital defect was briefly entertained . The patient was treated by radical excision of the occipital cyst with hair contents, the dermal sinus, and the abscesses through a suboccipital approach, followed by systemic antibiotic therapy with a good outcome . Pathologic examination revealed a dermoid cyst . CONCLUSION: Posterior fossa dermoid cyst should be considered in all children with occipital skin lesions, especially dermal sinus . CT scan and MRI are the methods of choice for further investigation of suspect congenital dermal lesions . Neurosurgical treatment of these malformations should be planned early to prevent the high incidence of infections such as bacterial meningitis and cerebellar abscess . Clinical presentation, diagnostic evaluation, and treatment of these rare lesions are reviewed. Chang Gung Med J, 2002 Sep, 25(9), 606 - 11 Levamisole aids in treatment of refractory oral candidiasis in two patients with thymoma associated with myasthenia gravis: report of two cases; Lai WH et al.; Oral candidiasis is associated with defects in cell-mediated immunity and is common among patients undergoing cytotoxic chemotherapy, or corticosteroid or antibiotic therapy, and those patients seropositive for AIDS and HIV (human immunodeficiency virus) . This paper demonstrates the important role of cell-mediated immunity in oral candidiasis in 2 cases of thymoma associated with myasthenia gravis . Both suffered from recurrent oral candidiasis after a thymectomy, radiotherapy, and chemotherapy . There was an initial good response to conventional antifungal therapy, which later became refractory . Lymphocyte subset quantitation showed a T cell deficiency and a decreased CD4/CD8 ratio . Levamisole, an immunomodulator, or an immunopotentiating drug was added as adjunctive therapy in combination with oral nystatin treatment . Oral candidiasis responded favorably, and substantial relief was obtained with a concurrent increase in T cells and the CD4/CD8 ratio . These findings clearly demonstrate a significant role of cell-mediated immunity in oral candidiasis, and that eradication of infection is dependent on the host defense mechanism. Drugs, 2002, 62 Suppl 1, 47 - 63 The role of myelopoietic growth factors in managing cancer in the elderly; Balducci L et al.; More than 50% of all malignancies are diagnosed in patients aged > 65 years and most cancer-related deaths occur in this population . Misconceptions about prognosis and treatment contribute to the undertreatment of elderly cancer patients and consequent poor outcomes . Although older patients have been excluded from cancer treatment trials in the past, response rates to chemotherapy in a variety of common cancers in otherwise healthy elderly patients are comparable to those attained in younger patients . Lower functional reserve in many organ systems alters the pharmacokinetics of chemotherapeutic drugs as well as the patient's response to treatment-induced toxicity . Except for myelosuppression and mucositis, otherwise fit elderly cancer patients are not at significantly enhanced risk of toxicity to chemotherapy . Severe neutropenia and related infection are encountered much more frequently during the treatment of elderly as compared with younger cancer patients . These lead to treatment delays, dose reductions and higher hospitalisation rates . Myelopoietic growth factor support reduces myelosuppression and the associated risk of severe infection, thereby allowing delivery of chemotherapy at full dose intensity . Beneficial responses to granulocyte colony-stimulating factor (G-CSF; filgrastim) in elderly patients have been found in aggressive non-Hodgkin's lymphoma with standard cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy and acute myeloid leukaemia (AML) during induction and consolidation chemotherapy . Granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) has been found to reduce myelosuppression in elderly AML patients receiving induction but not consolidation chemotherapy . These prophylactic treatments produce significant cost benefits because of the reduced hospitalisation and antibiotic use associated with neutropenia . To maximise positive outcomes, elderly patients should be included in clinical trials of new cancer agents . Since myelosuppression is the main risk factor for elderly patients undergoing chemotherapy, optimisation of growth factor support and the development of more effective and safer myelopoietic agents may improve success rates and reduce adverse events . Such information will lead to better management of cancer in older patients. Anat Histol Embryol, 2002 Jun, 31(3), 144 - 7 Study of the nervous tissue development in rainbow trout (Oncorhynchus mykiss) embryos treated with oxytetracycline; Arias P et al.; The purpose of this study was to discover whether the use of different doses of oxytetracycline causes any alteration in the development of nervous tissue in rainbow trout embryos . Five thousands eggs of females rainbow trout were divided into five groups . One group acted as control and the other four were administered with one of four doses of oxytetracycline, 0.025, 0.050, 0.100, or 0.201 microM, at the moment of fertilization . The eggs were incubated under pisciculture conditions to just before being ready to spring off . From the 10th day, 10-egg samples were taken regularly and fixed . Five were processed for histological techniques and stained with haematoxylin and eosin, cresyl fast violet and silver, the other five were homogenized for antibiotic detection . Histological alterations appeared in 37-day-old embryos, with an abnormal migration of the neuroblasts to the marginal layer of the neural cord, and alterations in the development of the lens and eye layers . Some embryos showed abnormal curvature of the spinal cord but these changes were not statistically significant. J Am Vet Med Assoc, 2002 Dec 1, 221(11), 1568 - 71 Fluoroquinolone-induced retinal degeneration in cats; Wiebe V et al.; Although the exact mechanism of fluoroquinolone-induced retinal degeneration in cats remains to be elucidated, it appears from the literature that a similar retinal degeneration can be reproduced from either direct intravitreal injection of high concentrations of drug or exposure to UVA light and drug in laboratory animals . (19,25) The fluoroquinolone molecular structure is also similar structurally to other drugs that are known to directly induce retinal degeneration, including the cinchona alkaloids and halogenated hydroquinolones . Experimental evidence suggests that both the parent compound and its breakdown products via metabolism and photodegradation are active inducers of retinal degeneration . (18,25) Development of toxicoses also appears to be dependent on the maximum concentration of active drug, metabolite, or both reaching the retina over time . (18) Evaluation of the literature suggests that risk factors predisposing cats to fluoroquinolone-induced retinal degeneration may include the following: 1) large doses or plasma concentrations of drug, 2) rapid IV infusion of the antibiotic, 3) prolonged courses of treatment, and 4) age . Theoretically, other risk factors may also be involved including the following: 1) prolonged exposure to UVA light while the antibiotic is being administered, 2) drug interactions, and 3) drug or metabolite accumulation from altered metabolism or reduced elimination . To date, there are no published reports suggesting that the dose of fluoroquinolones should be reduced in geriatric cats or those with renal or hepatic failure . However, accumulation of fluoroquinolone metabolites in dogs and of the parent compound in humans with decreased renal function has been reported . (8-10) In humans with decreased renal function has been reported . (8-10) humans, fluoroquinolone doses are typically decreased in response to the degree of renal impairment . (28) In general, all fluoroquinolone antibiotics should be reserved for severe or recurrent infections, and whenever possible their use should be based on results whenever possible their use should be based on results of culture and susceptibility tests . When indicated, the fluoroquinolones, including enrofloxacin, can be used with limited risk of developing retinal degeneration in cats, provided the manufacturer's guidelines are adhered to and dose reduction is considered in geriatric cats or those with renal impairment . Dosing on renal impairment . Dosing on exact body weight using split dosing (2.5 mg/kg, PO, q 12 h) and avoidance of rapid IV infusions, and drug interactions may help to reduce the risk of retinal degeneration in some cases . Furthermore, monitoring cats for mydriasis and avoidance of UVA light while undergoing treatment may also be of benefit . Further evaluation of the pharmacokinetics of enrofloxacin and the other fluoroquinolones is required in geriatric cats or those with mild to moderate renal or liver impairment to determine whether drug accumulation, elevated peak concentrations of drug, or both may be occurring in this subset of cats . Therapeutic monitoring of drug concentrations may not always be feasible because of time and cost, but renal panels with dose or frequency reduction in response to the degree of renal impairment and the site and severity of infection may help to reduce retinal toxicosis. Consum Rep, 2003 Jan, 68(1), 24 - 8 Of birds and bacteria. Complex regional pain syndrome and lyme borreliosis: two different diseases? Dept . of Infectious Diseases and Febrile Conditions, General Hospital Celje, Oblakova 5, SI-3000 Celje, Slovenia . branko.sibanc@guest.arnes.si Complex regional pain syndrome (CRPS) is a frequent complication appearing as pain of unexplained pathogenesis . Its association with Lyme borreliosis (LB) is fairly rare . In the presented clinical case, clinical features as well as the findings of radiological, radionuclide, neurophysiological and serological investigations pointed to an association between the two conditions . The patient fulfilled the criteria for both diagnoses, i.e . CRPS and LB . The subsequent antibiotic therapy resulted in a complete remission of both clinical entities. Health Policy Plan, 2002 Dec, 17 Suppl, 40 - 6 Quality and equity of private sector care for sexually transmitted diseases in South Africa; Chabikuli N et al.; The private sector plays a major role in the delivery of health care in South Africa . Over the past two decades, the quality and equity of such provision has been questioned internationally . A study was conducted in Gauteng Province to explore these issues, using care for sexually transmitted disease (STD) as a case study . Private general practitioners (GPs) were interviewed by telephone . Each was presented with a set of STD syndromes and requested to describe how s/he would manage the patient, first if the patient was insured, then secondly if the patient was paying cash (uninsured) . Reported prescriptions were costed and assessed for effectiveness against main causative pathogens using local standard clinical guidelines . Knowledge of recent developments in STD syndromic management and effectiveness of prescribed drugs was poor, especially for genital ulcer and pelvic inflammatory disease, and less than half the prescriptions overall were judged as effective . Although the effectiveness of prescriptions for insured and uninsured patients were similar, for most syndromes uninsured patients were offered significantly cheaper and less convenient antibiotic regimens . Effective regimens were also significantly more expensive than ineffective regimens . The results suggest that GPs' perceptions of patients' willingness or ability to pay for drugs have a bearing on quality of care . The paper concludes that STD patients who present to GPs are often offered poor quality of care, and the choice of inconvenient antibiotics impacts disproportionately on the poor . Improvements in the quality and equity of GP care will require interventions that address the factors that determine their behaviour. Chest, 2002 Dec, 122(6), 2042 - 9 Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study; Schaad UB et al.; OBJECTIVE: Recurrent upper respiratory tract infections (URTIs) are common illnesses in young children . As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children, the aim of the present trial was to investigate further its efficacy and safety in infection-prone children . METHODS: This is a randomized, double-blind, placebo-controlled, multicenter study with OM-85 in 232 patients aged 36 to 96 months with recurrent URTIs . Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5 . URTI was defined by the presence of at least two of the following: rhinitis, pharyngitis, cough, hoarseness, temperature > or = 38.5 degrees C, or URTI-related prescription of an antibiotic . RESULTS: OM-85-treated patients had a lower rate of URTIs (p < 0.05) . The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months, corresponding to a 16% reduction in the active-treatment group with respect to placebo . The largest difference was observed in the patients having had three or more URTIs during the study period; odds ratios for three or more URTIs were 0.51 (95% confidence interval, 0.29 to 0.91) and 0.65 (95% confidence interval, 0.37 to 1.11) after 5 months and 6 months, respectively . The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year . Patients' global assessment showed improvement in comparison to the previous season in the majority of the cases (OM-85, 78.4% of cases; placebo, 75.5%); however, there were more cases reporting worsening with placebo (6.4% vs 0.9%; p = 0.05) . CONCLUSIONS: OM-85 treatment significantly reduced the rate of URTIs, particularly in children with a history of frequent URTIs . Safety and tolerance of test medication were good, comparable to placebo. J Am Chem Soc, 2002 Dec 18, 124(50), 15001 - 5 Total synthesis of desferrisalmycin B; Dong L et al.; The first total synthesis of a naturally occurring siderophore antibiotic, desferrisalmycin B, is described, and the configuration of the unknown stereocenter is assigned . The synthesis features a synthetic strategy of constructing the novel amino-heptopyranoside component by stereoselective dihydroxylation followed by a Bose-modified Mitsunobu reaction . Through this convergent approach, other members of salmycins should also be synthetically accessible. Biochemistry, 2002 Dec 17, 41(50), 14879 - 84 Fusidic and helvolic acid inhibition of elongation factor 2 from the archaeon Sulfolobus solfataricus; De Vendittis E et al.; Fusidic acid (FA) and helvolic acid (HA) belong to a small family of naturally occurring steroidal antibiotics known as fusidanes . FA was studied for its ability to alter the biochemical properties supported by elongation factor 2 isolated from the archaeon Sulfolobus solfataricus (SsEF-2) . Both poly(Phe) synthesis and ribosome-dependent GTPase (GTPase(r)) were progressively impaired by increasing concentrations of FA up to 1 mM, whereas no effect was measured in the intrinsic GTPase of SsEF-2 triggered by ethylene glycol in the presence of barium chloride (GTPase(g)) . The highest antibiotic concentration caused inhibition of either poly(Phe) synthesis or GTPase(r) only slightly above 50% . A greater response of SsEF-2 was observed when HA was used instead of FA . HA caused even a weak impairment of GTPase(g) . A mutated form of SsEF-2 carrying the L452R substitution exhibited an increased sensitivity to fusidane inhibition in either poly(Phe) synthesis or GTPase(r) . Furthermore, both FA and HA were able to cause impairment of GTPase(g) . The antibiotic concentrations leading to 50% inhibition (IC(50)) indicate that increased fusidane responsiveness due to the use of HA or the L452R amino acid replacement is mutually independent . However, their combined effect decreased the IC(50) up to 0.1 mM . Despite the difficulties in reaching complete inhibition of the translocation process in S . solfataricus, these findings suggest that fusidane sensibility is partially maintained in the archaeon S . solfataricus . Therefore, it is likely that SsEF-2 harbors the structural requirements for forming complexes with fusidane antibiotics . This hypothesis is further evidenced by the observed low level of impairment of GTPase(g), a finding suggesting a weak direct interaction between the archaeal factor and fusidanes even in the absence of the ribosome . However, the ribosome remains essential for the sensitivity of SsEF-2 toward fusidane antibiotics. Biochemistry, 2002 Dec 17, 41(50), 14843 - 7 Electron paramagnetic resonance dynamic signatures of TAR RNA-small molecule complexes provide insight into RNA structure and recognition; Edwards TE et al.; Electron paramagnetic resonance (EPR) spectroscopy was utilized to investigate the correlation between RNA structure and RNA internal dynamics in complexes of HIV-1 TAR RNA with small molecules . TAR RNAs containing single nitroxide spin-labels in the 2'-position of U23, U25, U38, or U40 were incubated with compounds known to inhibit TAR-Tat complex formation . The combined changes in nucleotide mobility at all four sites, as monitored by their EPR spectral width, yield a dynamic signature for each compound . The multicyclic dyes Hoechst 33258, DAPI, and berenil bind to TAR RNA in a similar manner and gave nearly identical signatures . Different signatures were obtained for the acridine derivative CGP 40336A and the aminoglycoside antibiotic neomycin, which bind to different regions of the RNA . The dynamic signature for guanidinoneomycin was remarkably similar to that obtained for argininamide and is evidence for guanidinoneomycin binding to the same site as arginine 52 of the Tat protein, rather than to the neomycin binding site . The data presented here show that the dynamic signatures provide strong insights into RNA structure and recognition and demonstrate the value of EPR spectroscopy for the investigation of small molecule binding to RNA. Magy Seb, 2002 Oct, 55(5), 295 - 300 {Secondary aorto-enteral fistula--material of 22 years and literature review}; Szabo GV et al.; INTRODUCTION: Aorto-enteral fistula is a pathological communication between the aorta and the bowel lumen . In its secondary form is a dreaded, often fatal complication of the aorto-iliac operations . METHODS: We report 34 secondary fistulas, a great number of patients treated in the last 22 years . One can rarely find such a number in the literature . RESULTS: The incidence of secondary fistulas is 0.42% following aorto-iliac operations . We give a detailed description of diagnostics . We prefer in situ solutions (graft change, aorto-aortic interposition, iliac desobliteration, homograft or deep venous bypass, aorto-bifemoral bypass) to extra-anatomical bypasses . We emphasize the importance of the postoperative care, and the necessity of adequate antibiotic therapy . CONCLUSION: Despite improved operations and intensive care mortality is still high (55.88%) . We find that prevention is of great importance. Best Pract Res Clin Obstet Gynaecol, 2002 Dec, 16(6), 875 - 88 How, and how efficiently, can we treat Chlamydia trachomatis infections in women? Guaschino S, Ricci G. Several antichlamydial active drugs are available for both non-pregnant and pregnant women, potentially allowing effective prevention of the consequences and transmission of infection . The choice of treatment regimen not only has to consider efficacy, but also side-effects, compliance and the cost of antibiotic drugs . In recent years there have been no significant changes to the guidelines for treating Chlamydia trachomatis infection as no new antibiotic has been included . Inclusion of a new antichlamydial drug in the guidelines must be supported by suitable, randomized trials . Furthermore, how much it will be used in clinical practice will also depend on considerations of a pharmacoeconomic nature. J Am Geriatr Soc, 2002 Dec, 50(12), 1987 - 95 Nursing home facility risk factors for infection and hospitalization: importance of registered nurse turnover, administration, and social factors; Zimmerman S et al.; OBJECTIVES: Determine the relationship between a broad array of structure and process elements of nursing home care and (a) resident infection and (b) hospitalization for infection . DESIGN: Baseline data were collected from September 1992 through March 1995, and residents were followed for 2 years; facility data were collected at the midpoint of follow-up . SETTING: A stratified random sample of 59 nursing homes across Maryland . PARTICIPANTS: Two thousand fifteen new admissions aged 65 and older . MEASUREMENTS: Facility-level data were collected from interviews with facility administrators, directors of nursing, and activity directors; record abstraction; and direct observation . Main outcome measures included infection (written diagnosis, a course of antibiotic therapy, or radiographic confirmation of pneumonia) and hospitalization for infection (indicated on medical records) . RESULTS: The 2-year rate of infection was 1.20 episodes per 100 resident days, and the hospitalization rate for infection was 0.17 admissions per 100 resident days . Except for registered nurse (RN) turnover, which related to both infection and hospitalization, different variables related to each outcome . High rates of incident infection were associated with more Medicare recipients, high levels of physical/occupational therapist staffing, high licensed practical nurse staffing, low nurses' aide staffing, high intensity of medical and therapeutic services, dementia training, staff privacy, and low levels of psychotropic medication use . High rates of hospitalization for infection were associated with for-profit ownership, chain affiliation, poor environmental quality, lack of resident privacy, lack of administrative emphasis on staff satisfaction, and low family/friend visitation rates . Adjustment for resident sex, age, race, education, marital status, number of morbid diagnoses, functional status, and Resource Utilization Group, Version III score did not alter the relationship between the structure and process of care and outcomes . CONCLUSIONS: The association between RN turnover and both outcomes underscores the relationship between nursing leadership and quality of care in these settings . The relationship between hospitalization for infection and for-profit ownership and chain affiliation could reflect policies not to treat acute illnesses in house . The link between social factors of care (environmental quality, prioritizing staff satisfaction, resident privacy, and facility visitation) and hospitalization indicates that a nonmedical model of care may not jeopardize, and may in fact benefit, health-related outcomes . All of these facility characteristics may be modifiable, may affect healthcare costs, and may hold promise for other, less-medical, forms of residential long-term care. Afr J Reprod Health, 2001 Dec, 5(3), 47 - 53 Risk factors associated with maternal deaths in health units in Uganda; Mbonye AK; This study was conducted to assess the magnitude of maternal deaths in health units in Uganda, and the risk factors associated with such deaths . A retrospective study of maternal deaths in 20 hospitals and 54 randomly selected health centres was conducted in 12 randomly selected districts of Uganda . The reference period for documenting maternal deaths was September 1992 to September 1993 . The International Classification of Diseases 10 was used to define a maternal death . Data on maternal deaths and associated risk factors was obtained from admission and patient case notes . SPSS/PC statistical package was used to carry out advanced statistical analysis . Log linear analysis was used to rank risk factors for maternal deaths . A total of 418 maternal deaths and 75,000 live births were recorded, giving a maternal mortality ratio of 557 per 100,000 live births . Three hundred and sixty (86.1%) mothers died within one hour of admission . The risk factors identified were inadequate antibiotic supply, intravenous drug fluids and blood for transfusion in health units; non-use of family planning, use of traditional medicine; mothers aged 15-19 and 30-50 years . Others included those who had a history of two or more abortions and stillbirths; parity of five and above; and living within a distance of more than 10 km to the nearest health unit . We conclude that the focus on risk factors for maternal deaths have policy implications. Int J Cancer, 2003 Jan 20, 103(3), 352 - 9 Geldanamycin decreases Raf-1 and Akt levels and induces apoptosis in neuroblastomas; Kim S et al.; Neuroblastomas are the most common extracranial solid tumors of childhood . These tumors are associated with an overall poor prognosis, particularly for advanced stage disease . The benzoquinone ansamycin antibiotic, geldanamycin (GA), exhibits potent antitumor activity in certain cancer cell lines by destabilizing important signal transduction proteins (e.g., Raf-1 and Akt) . The purpose of our study was to determine whether GA can alter the expression of Raf-1 and Akt, which have been shown to be critical for neuronal cell survival, and induce apoptosis of neuroblastoma cells . Human neuroblastoma cells (SH-SY5Y, SK-N-SH and LAN-1) were treated with GA for a variable period of time . Cell viability was assessed with MTT assays . Apoptosis was assessed with DNA fragmentation ELISA, TUNEL-flow cytometric assay, Western blot and caspase activities . We found that GA decreases cell viability and induces apoptosis in the SH-SY5Y human neuroblastoma cell line . These effects were mediated through activation of caspase-9 and -3, mitochondrial release of cytochrome c and subsequent PARP cleavage . GA-induced apoptosis was associated with a reduction in the level and activity of Raf-1 and Akt . The importance of these proteins was further demonstrated by induction of apoptosis in SH-SY5Y cells by a combination of U0126 (MEK1/2 inhibitor) and LY294002 (an inhibitor of PI3K) . Similar to SH-SY5Y cells, other human neuroblastoma cells (SK-N-SH and LAN-1) were sensitive to the effects of GA-induced apoptosis . Taken together, our findings suggest that GA may be a novel therapeutic agent, which may be effective in the treatment of neuroblastomas . Clin Infect Dis, 2002 Dec 15, 35(12), 1566 - 71 Epub 2002 Dec 02. Amputation-sparing treatment by nature: "surgical" maggots revisited; Jukema GN et al.; Maggots were used as adjunct treatment for infected wounds that showed no response to the classical approach of wound debridement and antibiotic therapy . We summarize findings for 11 patients with necrotic wounds who received treatment with "surgical" maggots (100-2900 applied in 3-10 changes of dressing) for 11-34 days, which apparently aided in tissue remodeling and cure, and describe 2 typical patients in detail. Clin Infect Dis, 2002 Dec 15, 35(12), 1463 - 8 Epub 2002 Dec 03. Methodology for clinical trials involving patients with cancer who have febrile neutropenia: updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies; Feld R et al.; Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia . The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated . Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence . Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital . Response and safety parameters should be recorded along with readmission rates . If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy. Am J Respir Crit Care Med, 2002 Dec 15, 166(12 Pt 2), S57 - 61 Lactoperoxidase and hydrogen peroxide metabolism in the airway; Conner GE et al.; Hydrogen peroxide (H2O2) is known to play an important role in airway homeostasis . For this reason its levels and thus its synthesis and consumption are important mechanisms for controlling airway functions . We have identified the major macromolecular consumer of H2O2 in sheep airway secretions to be lactoperoxidase (LPO), a heme peroxidase previously studied in milk and saliva . This enzyme uses H2O2 to oxidize the anion thiocyanate to an antibiotic compound that prevents growth of bacteria, fungi, and viruses . LPO was isolated from sheep airways and proved to be a major constituent comprising about 1% of the soluble protein in airway secretions . The isolated airway LPO was catalytically active and displayed the enzymatic characteristics previously described for the enzyme isolated from bovine milk . Airway LPO activity was shown to increase the rate of bacterial clearance from sheep airways . The role of this enzyme in the airway host defense strongly suggests that an active H2O2 production system exists to supply appropriate substrate for the enzyme . The identity of this H2O2 synthesis system is an important, yet unknown feature of airway oxygen radical metabolism. Neurobiol Aging, 2002 Nov-Dec, 23(6), 1031 - 8 Metal complexing agents as therapies for Alzheimer's disease; Bush AI; Modern research approaches into drug development for Alzheimer's disease (AD) target beta-amyloid (Abeta) accumulation in the brain . The main approaches attempt to prevent Abeta production (secretase inhibitors) or to clear Abeta (vaccine) . However, there is now compelling evidence that Abeta does not spontaneously aggregate, but that there is an age-dependent reaction with excess brain metal (copper, iron and zinc), which induces the protein to precipitate into metal-enriched masses (plaques) . The abnormal combination of Abeta with Cu or Fe induces the production of hydrogen peroxide, which may mediate the conspicuous oxidative damage to the brain in AD . We have developed metal-binding compounds that inhibit the in vitro generation of hydrogen peroxide by Abeta, as well as reverse the aggregation of the peptide in vitro and from human brain post-mortem specimens . Most recently, one of the compounds, clioquinol (CQ; a USP antibiotic) was given orally for 9 weeks to amyloid-bearing transgenic mice, and succeeded in markedly inhibiting Abeta accumulation . On the basis of these results, CQ is being tested in clinical trials. J Am Acad Orthop Surg, 2002 Nov-Dec, 10(6), 379 - 84 Timing of closure of open fractures; Weitz-Marshall AD et al.; Traditionally, closure of open fractures after initial debridement has been delayed to minimize the risk of complications, particularly infection . This practice developed before the widespread use of systemic antibiotics, local antibiotic bead pouches, advanced debridement methods, and improved fracture stabilization techniques . Current evidence indicates that infections after treatment of open fractures frequently are not caused by initial contaminating organisms but often are acquired in the hospital . Recent studies comparing primary with delayed closure have not demonstrated an increased rate of complications . Considering the improvements in open fracture wound care, the increasing incidence of resistant nosocomial infections, and the cost implications of a dogmatic delayed-closure strategy, wound care protocols for open fractures should be reevaluated . Because of lack of data specifically addressing the timing of closure of such wounds, studies comparing primary versus delayed closure are needed. Chir Ital, 2002 Sep-Oct, 54(5), 693 - 8 {Diverticular disease: complications and treatment}; Cavallaro A et al.; This study reports on 10 years of experience in observing diverticular disease . The study considers 77 patients, 41 males and 36 females, aged from 50 to 88 years (mean age: 70 years), observed from January 1991 to December 2001 . Sixty-two patients were admitted from the Accident and Emergency Unit and 15 were elected patients . Five patients underwent emergency surgery, while 72 received only antibiotic therapy . The overall mortality rate was 0 . The morbidity rate was 22% in those patients undergoing emergency surgery . In only one of the elected patients was wound suppuration detected . Diverticular disease, in most cases, is treated by antibiotic therapy alone, but in 30% of cases surgery is necessary . Colon resection and immediate anastomosis are the first choice operation also in the emergency setting, provided local conditions (inflammation, septic contamination) make anastomosis safe . In patients with major peritoneal contamination, Hartman's operation and subsequent recanalization after 6 months are to be preferred. J Spinal Disord Tech, 2002 Dec, 15(6), 513 - 8 Esophageal perforation after fracture of the cervical spine: case report and review of the literature; Nerot C et al.; We present a posttraumatic esophageal tear that occurred in a 55-year old patient after a truck accident . He sustained a two-level injury with a type II odontoid fracture and a unilateral fracture of the left superior articular process of C6 with an incomplete quadriplegia at C5 . Both lesions were treated nonoperatively . The tear was attributed to the stretching of the esophagus over anterior degenerative spurs at the level of the lesion (C5-C6) during hyperextension . The diagnosis of the esophageal perforation was delayed for 6 days . The treatment consisted of surgical debridement, volume expansion, antibiotic therapy, hyperbaric oxygenation, assisted ventilation, and esophageal exclusion . A complete review of the literature was performed. Obstet Gynecol, 2002 Dec, 100(6), 1271 - 5 Hysterectomy for the massive leiomyomatous uterus; Unger JB et al.; OBJECTIVE: To determine if the complication rate of abdominal hysterectomy is increased in women with greatly enlarged myomatous uteri . METHODS: Three groups of women undergoing abdominal hysterectomy were analyzed according to uterine size: group 1, 208 women with uteri less than 500 g; group 2, 63 women with uterine weights of 500-999 g; and group 3, 47 women with leiomyomata whose uteri weighed at least 1000 g . Logistic regression was used to compare the groups on the risks of having at least one major complication . Adjusted comparisons on other surgical outcomes were performed using a logistic model (for qualitative variables) or a general linear model (for quantitative variables) . RESULTS: The risk of experiencing at least one perioperative complication, including blood loss over 500 mL, perioperative blood transfusion, major organ injury, therapeutic antibiotic use, and hospital readmission, increased significantly with uterine weight (P =.006) . Group 3 women were at greater risk of having at least one of these complications than either group 1 or group 2 women, with adjusted odds ratios of 3.42 (95% confidence interval {CI} 1.62, 7.25) and 2.64 (95% CI 1.14, 6.13), respectively . Estimated blood loss with surgery also increased with increasing uterine weight (P <.001) . Mean estimated blood losses for the study groups were 555.8 +/- 386.5 mL (group 3), 464.3 +/- 285.2 mL (group 2), and 387.6 +/- 281.4 mL (group 1) (P =.032) . CONCLUSION: The complication rate from hysterectomy increases with increasing uterine weight, due mainly to an increased blood loss associated with surgery for larger uteri. Int J Biochem Cell Biol, 2003 Jan, 35(1), 79 - 85 Development of a ponasterone A-inducible gene expression system for application in cultured skeletal muscle cells; Xiao YY et al.; The goal of this study was to develop an inducible gene expression system to assess functions of specific proteins in differentiated cultured skeletal muscle . We utilized and modified the ecdysone inducible system because others have used this system to express exogenous genes in vitro and in transgenic animals . A limitation of the commercially-available ecdysone system is its constitutive expression in all tissues . Hence, its application in vivo would result in expression of a cloned gene in undifferentiated and differentiated tissues . To target its expression to muscle, we removed the constitutively-active CMV promoter of pVgRXR and replaced it with a skeletal muscle alpha-actin promoter so that the regulatory features of the system would be expressed in differentiated muscle cells . We transfected our newly designed expression system into L8 muscle myoblasts and established stable cell lines via antibiotic selection . We determined that reporter gene activity was induced by ponasterone A in myotubes, a differentiated muscle phenotype, but not in myoblasts (undifferentiated cells) . This proved the validity of the concept of an inducible muscle-specific expression system . We then determined that beta-galactosidase expression was dependent upon the dose of ponasterone A and duration of exposure to inducer . This creates potential to regulate both the level of expression and duration of expression of a cloned gene in differentiated muscle. J Org Chem, 2002 Dec 13, 67(25), 9054 - 60 Activation of leinamycin by thiols: a theoretical study; Breydo L et al.; Reaction of thiols with the 1,2-dithiolan-3-one 1-oxide heterocycle found in leinamycin (1) results in the conversion of this antitumor antibiotic to a DNA-alkylating episulfonium ion (5) . While the products formed in this reaction have been rationalized by a mechanism involving initial attack of thiol on the central sulfenyl sulfur (S2') of the 1,2-dithiolan-3-one 1-oxide ring, the carbonyl carbon (C3') and the sulfinyl sulfur (S1') of this heterocycle are also expected to be electrophilic . Therefore, it is important to consider whether nucleophilic attack of thiol at these sites might contribute either to destruction of the antibiotic or conversion to its episulfonium ion form . To address this question, we have used computational methods to examine the attack of methyl thiolate on each of the three electrophilic centers in a simple analogue of the 1,2-dithiolan-3-one 1-oxide heterocycle found in leinamycin . Calculations were performed at the MP2/6-311+G(3df,p)//B3LYP/6-31G level of theory with inclusion of solvent effects . The results indicate that the most reasonable mechanism for thiol-mediated activation of leinamycin involves initial attack of thiolate at the S2'-position of the antibiotic's 1,2-dithiolan-3-one 1-oxide heterocycle, followed by conversion to the 1,2-oxathiolan-5-one intermediate (3). Cancer, 2002 Dec 15, 95(12), 2562 - 70 Long-term cognitive outcome, brain computed tomography scan, and magnetic resonance imaging in children cured for acute lymphoblastic leukemia; Iuvone L et al.; BACKGROUND: Prevention of meningeal recurrence achieved by intrathecal methotrexate (MTX) and systemic chemotherapy is part of standard acute lymphoblastic leukemia (ALL) treatment . Cranial irradiation has been a routine part of past protocol treatment but is currently reserved only for select subsets of patients . Central nervous system (CNS) prophylaxis may cause brain abnormalities such as intracerebral calcifications, cerebral atrophy, and white matter alterations . In addition, long-term neuropsychologic sequelae following CNS prophylaxis have been investigated marginally in children cured for ALL . METHODS: To explore possible correlations between neuroimaging findings and neuropsychologic outcome, we used detailed cognitive tests to evaluate 21 children with ALL who received cranial irradiation (range, 18-24 Gy) plus intrathecal MTX as CNS prophylaxis . All children were followed prospectively once a year by cerebral computed tomographic scan and magnetic resonance imaging . All patients had continuous complete disease remission for at least 4 years and cognitive tests were performed after neuroradiologic examinations . RESULTS: White matter abnormalities were associated with poor performance only in a task exploring visual motor integration in about 50% of patients . Intracerebral calcifications correlate with the number of intrathecal MTX doses and with low scores in total intellectual quotient, performance intellectual quotient, and significant impairment in attention and visual motor integration tests . Girls are more vulnerable to the effects of CNS prophylaxis, whereas age at treatment and radiotherapy dose are not relevant to neuropsychologic outcome . CONCLUSIONS: Our results indicate the need for careful follow-up of children's cognitive abilities because global intellectual measures often fail to detect specific disorders that may cause learning difficulties . Moreover, as the clinical implications of neuroimaging findings are often limited, periodic extensive evaluation by specific neurocognitive tests of mental abilities is recommended to detect early signs of cognitive impairment . J Am Chem Soc, 2002 Dec 11, 124(49), 14655 - 62 Stereoselective synthesis of pamamycin-607; Jeong EJ et al.; A macrodiolide antibiotic pamamycin-607 was synthesized by joining two hydroxy acid components . Three cis-2, 5-disubstituted tetrahydrofuran rings in the molecule were stereoselectively prepared by radical cyclization reactions of beta-alkoxyvinyl ketone intermediates and a beta-alkoxymethacrylate substrate . The key step of the synthesis is characterized by the predominant threo product formation in the radical cyclization reaction of a beta-alkoxymethacrylate intermediate. Mutat Res, 2002 Dec, 512(2-3), 121 - 34 Genotoxicity of streptozotocin; Bolzan AD et al.; Streptozotocin (Streptozocin, STZ, CAS No . 18883-66-4) is a monofunctional nitrosourea derivative isolated from Streptomyces achromogenes . It has broad spectrum antibiotic activity and antineoplastic properties and is often used to induce diabetes mellitus in experimental animals through its toxic effects on pancreatic beta cells . STZ is a potent alkylating agent known to directly methylate DNA and is highly genotoxic, producing DNA strand breaks, alkali-labile sites, unscheduled DNA synthesis, DNA adducts, chromosomal aberrations, micronuclei, sister chromatid exchanges, and cell death . This antibiotic was found to be mutagenic in bacterial assays and eukaryotic cells . STZ is also carcinogenic; a single administration induces tumors in rat kidney, liver, and pancreas . Several lines of evidence indicate that free radicals are involved in the production of DNA and chromosome damage by this compound . Because of the use of STZ as an antineoplastic agent, the study of its genotoxicity has considerable practical significance . The purpose of this review is to present our current knowledge regarding the genotoxicity of STZ. Vet Dermatol, 2002 Dec, 13(6), 331 - 6 Pemphigus foliaceus in a goat; Pappalardo E et al.; A 7-year-old-female goat was referred with a 3-month history of chronic dermatitis, which partially responded to combined corticosteroid and antibiotic therapy . At dermatological examination diffuse alopecia, pustules and crusts were observed on the head, neck, dorsum and perianal area . Dermatophyte culture and skin scrapings were negative . Trichoscopic examination revealed a concurrent infestation with Damalinia caprae, which was successfully treated with ivermectin . Cytological examination of pus from intact pustules revealed nondegenerate neutrophils, absence of bacteria and numerous nucleated, irregularly shaped keratinocytes . Histopathological examination of lesional skin revealed intracorneal pustules containing neutrophils and acantholytic cells, and a mixed cell superficial perivascular dermatitis . Immunohistochemical stains of lesional skin showed intercellular IgG deposits in the spinous layer . Remission of the dermatitis was obtained with injectable dexamethasone-21-isonicotinate, every two months for one year . This is the first report to describe the cytological appearance of impression smears from intact pustules of pemphigus foliaceus in a goat and to document the presence of IgG deposits in lesional skin by means of immunohistochemistry. Acta Paediatr, 2002, 91(11), 1179 - 82 Differential diagnosis and clinical course of autoimmune neutropenia in infancy: comparison with congenital neutropenia; Taniuchi S et al.; AIM: Autoimmune neutropenia in infancy (AIN) is caused by granulocyte-specific autoantibodies . Clinical presentation and diagnosis have not been well studied, resulting in cumbersome diagnostic investigations and unnecessary treatment such as granulocyte colony-stimulating factor (G-CSF) therapy . METHODS: Clinical, laboratory and immunological data of 18 infants with AIN were evaluated . Granulocyte-specific autoantibodies were detected by the direct granulocyte immunofluorescence test (D-GIFT), indirect granulocyte immunofluorescence test (I-GIFT) and immunoblotting . RESULTS: The average age of onset and resolution of neutropenia in AIN was 7.4 +/- 3.4 mo (mean +/- SD) and 20.4 +/- 4.9 mo, respectively . Sixteen of the 18 patients presented with mild infectious symptoms; the other 2 patients were detected by chance and presented with no infectious symptoms . D-GIFT was positive in all patients, and I-GIFT was positive in 17 of these 18 patients . Most patients showed preferential binding to neutrophils from NA(1 + 2-)-phenotyped donors by 1-GIFT and immunoblotting . An antibiotic (sulfamethoxazole-trimethoprim) was given to 15 patients for prophylaxis . G-CSF was given to only one infectious patient . CONCLUSION: A combination of diagnostic tests for the detection of granulocyte-specific autoantibodies was useful in diagnosing AIN, thus avoiding unnecessary investigations . Continuous treatment with G-CSF was not necessary for prophylaxis, even if neutrophil counts were extremely low. Am J Infect Control, 2002 Dec, 30(8), 476 - 89 Guidelines for the prevention of intravascular catheter-related infections; O'grady NP et al.; BACKGROUND: Although many catheter-related bloodstream infections (CR-BSIs) are preventable, measures to reduce these infections are not uniformly implemented . OBJECTIVE: To update an existing evidenced-based guideline that promotes strategies to prevent CR-BSIs.Data Sources: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles.Studies Included: Laboratory-based studies, controlled clinical trials, prospective interventional trials, and epidemiological investigations.Outcome Measures: Reduction in CR-BSI, catheter colonization, or catheter-related infection . SYNTHESIS: The recommended preventive strategies with the strongest supportive evidence are education and training of healthcare providers who insert and maintain catheters; maximal sterile barrier precautions during central venous catheter insertion; use of a 2% chlorhexidine preparation for skin antisepsis; no routine replacement of central venous catheters for prevention of infection; and use of antiseptic/antibiotic impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (i.e . education and training, maximal sterile barrier precautions and 2% chlorhexidine for skin antisepsis) . CONCLUSION: Successful implementation of these evidence-based interventions can reduce the risk for serious catheter-related infection. Curr Opin Biotechnol, 2002 Oct, 13(5), 448 - 52 Latest developments and in vivo use of the Tet system: ex vivo and in vivo delivery of tetracycline-regulated genes; Corbel SY et al.; In June this year, the tetracycline-regulated gene expression system (tet system) celebrated its tenth "birthday" . In the past ten years a continuous stream of changes made to the tet system's basic components has led to a remarkable improvement in its overall performance . It was not until this year, however, that the full benefits of these improvements became apparent . In particular, usage of the tet system is no longer limited to immortalized cell lines and transgenic animals . In this review, we will describe the obstacles encountered in delivering the tet system's components to primary cells and tissues as well as the methods now used to overcome them . We will also focus on a novel system that is conceptually similar but based on different antibiotic/transcription factor pairs. Gastroenterol Hepatol, 2002 Dec, 25(10), 585 - 8 {Endoscopic treatment combined with extracorporeal shock wave lithotripsy of difficult bile duct stones}; Mora J et al.; OBJECTIVES: The aim of this study was to determine the safety and effectiveness of extracorporeal shock wave lithotripsy (ESWL) in difficult bile duct stones resistant to endoscopic extraction . PATIENTS AND METHOD: From January 1997 to February 2002, combined treatment with endoscopy and ESWL was used in 19 patients who had undergone unsuccessful endoscopic bile duct stone extraction after sphincterotomy . The procedure was carried out using analgesic and sedative drugs or deep sedation, prophylactic antibiotic therapy, and monitoring of vital signs . Bile duct stone localization was performed by contrast injection through nasobiliary drainage and fluoroscopy . After each ESWL session, lavage was performed through drainage and stone fragments were extracted endoscopically . RESULTS: The 19 patients presented high surgical risk due to advanced aged and/or concomitant diseases . All presented jaundice and pain and nine (47.3%) presented associated cholangitis . Thirty ESWL sessions were performed (1.57 sessions per patient), with a mean of 2,120 shock waves per session . In 16 of the 19 patients (84.2%), combined treatment with ESWL and subsequent instrumental endoscopic extraction achieved complete clearance of the biliary tract . The treatment failed in 3 patients who were referred for surgical treatment . No early or late complications were observed, except in one patient who presented a self-limiting febrile syndrome . CONCLUSIONS: Therapeutic endoscopy combined with ESWL is safe and effective in patients with difficult bile duct stones . It represents a therapeutic alternative in patients at high surgical risk. Pediatr Infect Dis J, 2002 Nov, 21(11), 1081 - 3 Percutaneous transhepatic alcoholization: a new therapeutic strategy in children with chronic granulomatous disease and liver abscess; Alberti D et al.; Children affected with chronic granulomatous disease develop severe infections, which frequently evolve to abscess . In most instances the liver is involved . We report a case of liver abscess successfully treated by percutaneous transhepatic alcoholization after antibiotic therapy and percutaneous drainage had failed . This procedure avoided the need for hepatic resection, which is associated with high morbidity in such patients. Int J Colorectal Dis, 2003 Jan, 18(1), 55 - 62 Epub 2002 May 09. Rifaximin improves symptoms of acquired uncomplicated diverticular disease of the colon; Latella G et al.; BACKGROUND AND AIMS: We examined the efficacy of cyclic long-term administration of rifaximin, a broad spectrum, poorly absorbable antibiotic, in obtaining symptom relief in a large series of patients with uncomplicated diverticular disease, and compared the incidence of episodes of diverticulitis in the group treated with rifaximin to that in a group receiving fiber supplementation only . PATIENTS AND METHODS: In a multicenter, prospective, open trial, 968 outpatients with uncomplicated symptomatic diverticular disease were randomized to either fiber supplementation with 4 g/day glucomannan plus 400 mg rifaximin twice daily for 7 days every month ( n=558) or 4 g/day glucomannan alone ( n=346) . Clinical evaluation was performed on admission and at 4-month intervals for 12 months . RESULTS: After 12 months the group treated with glucomannan + rifaximin showed fewer symptoms (abdominal pain/discomfort, bloating, tenesmus, diarrhea, abdominal tenderness) and a lower global symptomatic score . Overall 56.5% of the patients treated with glucomannan + rifaximin and 29.2% of those treated with glucomannan alone were asymptomatic at 12 months ( P<0.001) . The rate of complications (diverticulitis and rectal bleeding) was 1.34% in the rifaximin + glucomannan group and 3.22% in the glucomannan alone group ( P<0.05) . CONCLUSION: Cyclic administration of rifaximin is effective in obtaining symptom relief in uncomplicated diverticular disease of the colon . The incidence of episodes of diverticulitis in the group treated with rifaximin was lower than that in the group treated with glucomannan alone. J SOGC, 2000 Sep, 22(9), 684 - 689 CAESAREAN SECTION ON REQUEST; Jibodu O et al.; Advances in surgical techniques, anaesthesia, thromboprophylaxis, blood transfusion, antibiotic therapy, and improved general health have changed Caesarean section (CS) from a procedure associated with considerable risk of morbidity and mortality to mother and/or fetus to one with little risk . Although CS is performed for obstetric indications, the threshold is lower, including CS on request, leading to a trend of rising CS rates . A main focus of debate is CS request by women who subjectively perceive benefit from an elective CS . The issues involved are complicated and the implications far-reaching . When risks, benefits, and costs are assessed, the perceived advantage of vaginal delivery over elective CS may be diminished or eliminated and decisions on the mode of delivery may be based on preferences rather than statistics . In this article, we outline some of the arguments for and against CS on request and the opinion of the Ethics Committee of the International Federation of Obstetricians and Gynaecologists (FIGO). J Craniofac Surg, 2002 Nov, 13(6), 765 - 8 Sclerosing osteomyelitis of Garré periostitis ossificans; Belli E et al.; Sclerosing osteomyelitis of Garre is a rare syndrome; the mandible is the most commonly affected bone segment in the cervicofacial region . This chronic disease is characterized by a nonsuppurative ossifying periostitis with subperiosteal bone formation, commonly reactive to a mild infection or irritation . The differential diagnosis must be made with similar clinical conditions with hard mandibular swelling associated with bony sclerosis . Presumptive diagnosis can be achieved by radiology, but such diagnosis must be confirmed by histology . The aim of therapy is to remove the cause when recognized, aided by an adequate antibiotic therapy . Clinical, radiographic, and histologic features are presented in this case report. Respiration, 2002, 69(6), 521 - 5 Invasive pulmonary aspergillosis; Kristan SS et al.; BACKGROUND: Invasive pulmonary aspergillosis usually occurs in immunocompromised patients . Mild abnormality of host defence is usually present in the chronic necrotising form of the disease . Acute aspergillus pneumonia usually affects patients who are seriously immunocompromised . OBJECTIVES: The purpose of the study was to highlight the possibility of occurrence of invasive pulmonary aspergillosis also in patients with mild abnormality of host defence . METHODS: In a retrospective study 6 patients were analysed . The inclusion criterion was evidence of Aspergillus sp . invasion in lung tissue . Lung tissue was obtained by biopsy or post mortem examination . RESULTS: There were 4 patients with acute aspergillus pneumonia . Two of them were severely immunocompromised - one with dermatomyositis, who was treated with high doses of corticosteroids and methotrexate, and the other with undiscovered miliary tuberculosis, who was treated for myelodysplastic syndrome instead with low doses of corticosteroids . The other 2 had mild immunosuppression: one was suffering from sarcoidosis and was treated with low doses of corticosteroids, the other had dilated cardiomyopathy, renal insufficiency and diabetes mellitus . The two patients with chronic necrotising pulmonary aspergillosis had mild abnormality of host defence: one had reactivation of tuberculosis and diabetes mellitus, the other had inactive tuberculosis and aspergilloma . CONCLUSIONS: Invasive pulmonary aspergillosis must be considered also in patients with mild immunosuppression and pulmonary infiltrates which do not respond to conventional treatment with antibiotic chemotherapy . The key to the diagnosis of invasive pulmonary aspergillosis is the histopathological demonstration of fungal invasion in lung tissue . Front Biosci, 2003 Jan 01, 8, e36 - 43 Chlamydial infections of the cardiovascular system; Kuo CC et al.; This paper presents a review on cardiovascular diseases which can be caused by chlamydial infection with the emphasis in the recent development in association between Chlamydia pneumoniae and cardiovascular disease . The review includes seroepidemiologic observations; the discovery of C . pneumoniae in atheromatous plaques; in vivo studies using animal models indicating that C . pneumoniae is a co-risk factor of hyperlipidemia for atherosclerosis; in vitro studies demonstrating putative mechanisms by which C . pneumoniae could contribute to the immunopathology of atherosclerosis; and early promising antibiotic intervention studies. J Gynecol Obstet Biol Reprod (Paris), 2002 Nov, 31(7 Suppl), 5S114 - 23 {Special management for threatened preterm delivery in multiple pregnancies}; Vayssiere C; Spontaneous prematurity is more frequent in multiple than singleton pregnancies . It is estimated that 72% of the multiple pregnancies delivered before 33 weeks are spontaneous births, compared with 58% among singletons (NP3) . As in singleton pregnancies, uterine contractions, close together, often precede preterm delivery by several days (NP2) . The benefits of home tocodynamometry for patients who have already been hospitalized for threatened preterm delivery (TPD) (NP4) is difficult to assess from the data currently available, but it has not been shown to provide any benefits in a population of asymptomatic twin pregnancies (NP1) . Cervical ultrasound appears to have good predictive value for preterm delivery when performed for TPD (NP3), although again few data are available . The efficacy of tocolysis appears similar to that for singleton pregnancies (NP3) . Although the lack of data prevents us from judging the efficacy of tocolytics such as calcium channel blockers or oxytocin antagonists, it seems logical to use them as first-line drugs, especially because of the increased risk of pulmonary edema in multiple pregnancies with Bmimetics (NP3) . Antenatal corticosteroid therapy appears to be less beneficial in multiple than singleton pregnancies (NP3) . Pharmacological studies suggest that the dose currently used may be insufficient for multiple pregnancies (NP3) . While awaiting results from clinical studies comparing the efficacy of higher doses, we must for now recommend antenatal corticosteroid therapy only at the usual doses . While the rate of in utero transfers to level III facilities is nearly 85% in the case of severe TPD (NP4), this practice must be encouraged still more in view of the benefits of inborn status compared with postnatal transfer . Finally, delayed-interval delivery is a relatively rare obstetrical practice that should be considered on a case-by-case basis when the first fetus is born before 26 weeks . This approach requires tocolysis and antibiotic therapy . The usefulness of cerclage in this situation has yet to be demonstrated . A delayed-interval delivery can prolong the pregnancy by an average of 15 to 30 days (NP4). Nephrol Dial Transplant, 2002 Dec, 17(12), 2196 - 203 Cost-effectiveness of three strategies of managing tunnelled, cuffed haemodialysis catheters in clinically mild or asymptomatic bacteraemias; Mokrzycki MH et al.; BACKGROUND: Immediate tunnelled, cuffed catheter (TCC) removal is the current standard of care when bacteraemia is associated with severe clinical symptoms . When minimal or no symptoms are present, the optimal strategy of TCC management is controversial . The following three strategies have been proposed: TCC 'salvage' (antibiotic administration without TCC removal), TCC exchange over a guidewire with antibiotics or immediate TCC removal with delayed reinsertion and antibiotics . METHODS: We developed a decision-analytic model to assess the cost-effectiveness of each strategy for episodes of TCC-associated bacteraemia presenting with minimal symptoms, in a hypothetical cohort of haemodialysis patients followed for a 3 month period . Data regarding the probability of treatment failure due to recurrent infection for each strategy, secondary infectious complications and patient mortality were obtained from existing clinical trials and from the 1998 United States Renal Data System database . Costs were substituted with the current 2000 New York hospital charges . RESULTS: Tunnelled, cuffed catheter exchange over a guidewire was associated with a reduction in net charges of $5241 and $750 when compared with TCC salvage and immediate TCC removal, respectively . The expected 3 month patient survival for TCC guidewire exchange and immediate TCC removal were similar (93%), whereas survival for TCC salvage was worse (89%) . Tunnelled, cuffed catheter guidewire exchange remained the most cost-effective strategy when the probability of treatment failure with recurrent bacteraemia in 3 months was <25% for this strategy . CONCLUSIONS: Tunnelled, cuffed catheter guidewire exchange is the most cost-effective strategy of catheter management when mild or no symptoms are present. Ann Pharmacother, 2002 Dec, 36(12), 1938 - 43 Fluoroquinolone treatment of community-acquired pneumonia: a meta-analysis; Salkind AR et al.; OBJECTIVE: To determine the role of newer fluoroquinolones (FQs) for adults with community-acquired pneumonia (CAP) whose level of illness allows treatment with an oral antibiotic . METHODS: Meta-analysis of randomized controlled trials comparing a macrolide, beta-lactam, or doxycycline antibiotic with a newer oral FQ for the treatment of CAP . RESULTS: Patients (5118), most of whom were <60 years of age and free of coexisting diseases, were enrolled in 13 studies comparing an oral macrolide or beta-lactam antibiotic with an FQ for the treatment of CAP . No previous study compared doxycycline with an FQ . In the intention-to-treat (ITT) population, no trial demonstrated significant differences between FQs or alternative therapies . Summary estimates showed a statistically significant advantage in favor of the FQs in both the ITT (OR 1.22; 95% CI 1.02 to 1.47; p = 0.03) and evaluable populations (OR 1.37; 95% CI 1.11 to 1.68; p = 0.003) . The number needed to treat for an FQ advantage was 33 (95% CI 17 to 362) in the ITT population and 37 (95% CI 22 to 121) in the evaluable population . Treatment failures represented slow symptom resolution; no deaths were reported . CONCLUSIONS: The newer oral FQs showed modest therapeutic benefit compared with the studied alternative antibiotics in adults with CAP . Based on the number needed to treat from the ITT population as a measure of treatment effect, clinicians must decide whether treating 33 patients with an FQ to prevent a single therapeutic failure with another studied antibiotic warrants use of an agent from that class for an illness with a generally favorable outcome regardless of antibiotic selection, and at a time when FQ resistance may be increasing. Dig Dis Sci, 2002 Nov, 47(11), 2424 - 33 In vivo detection of morphological and microvascular changes of the colon in association with colitis using fiberoptic confocal imaging (FOCI); McLaren WJ et al.; Using a well-established rodent model of inflammatory bowel disease (IBD), the present study examined changes in the microvasculature of the colonic mucosa in association with ulcerative colitis (UC) . The results were compared to microscopic alterations in tissue morphology to establish a temporal relationship between microcirculatory dysfunction and IBD pathology . Mild colitis was induced in rats by the oral consumption of 5% dextran sulfate sodium (DSS) in drinking water . Control animals were provided with water ad libitum . After 3, 5, and 7 days of oral ingestion of DSS, anesthetized rats were laparotomized . The mucosal surface of the distal colon was then examined using fiber optic confocal imaging (FOCI; excitation 488 nm argon ion laser, detection above 515 nm) . Changes in the mucosal architecture were examined following the topical application of the fluorescent dye, tetracycline hydrochloride . Tetracycline hydrochloride, an antibiotic used widely in clinical medicine, enabled imaging of the crypts at the surface of the mucosa . Spatial changes in the microvascular structure were assessed following the intravenous administration of fluorescein isothiocyanate dextran (FITC-dextran) . Confocal images were correlated with clinical parameters, including weight loss, occult blood, and stool consistency . Attenuation of the colonic epithelium was detected on day 3 colitis . Morphological changes including crypt loss, crypt distortion, and inflammatory cell infiltrate were detected on day 5 and day 7 colitis . Dual channel imaging showed the mucosal capillary network outlining the stromal confines of the mucus-secreting glands in control tissue . Experimental colitis resulted in diffuse hypervascularity and tortuosity of the capillary vessels . Evidence of increased vessel leakiness (leakage of FITC-dextran from the lumen) was first detected on day 5 colitis . Complete disruption of the normal honeycomb pattern of the vessels and capillary dilation was evident after 7 days of DSS ingestion . These findings suggest that the pathogenesis of ulcerative colitis is associated with changes in the vascular architecture as demonstrated in vivo using confocal microscopy. Orthopedics, 2002 Nov, 25(11), 1247 - 52 The application of bioimplants in the management of chronic osteomyelitis; Wang J et al.; The management of musculoskeletal infections is an increasing challenge to clinicians . Bioimplants provide a unique system for skeletal specific drug delivery . Antibiotic-impregnated beads and spacers can be used to treat chronic osteomyelitis and deep soft-tissue infections locally with higher antibiotic concentrations, while avoiding potential systemic side effects. Cancer Chemother Pharmacol, 2002 Dec, 50(6), 497 - 500 Epub 2002 Oct 22. Mylotarg combined with topotecan and cytarabine in patients with refractory acute myelogenous leukemia; Cortes J et al.; PURPOSE: Mylotarg, a humanized anti-CD33 antibody linked to an antitumor antibiotic, is approved for the treatment of patients with relapsed acute myeloid leukemia (AML) . Topotecan and cytarabine (ara-C) is an effective anti-AML regimen . A pilot study of Mylotarg combined with topotecan and ara-C (MTA) was conducted in patients with refractory AML . METHODS: MTA consisted of Mylotarg 9 mg/m(2) intravenously (i.v.) over 2 h on day 1, ara-C 1 g/m(2) over 2 h i.v . on days 1 through 5, and topotecan 1.25 mg/m(2) by continuous infusion i.v . on days 1 through 5 . RESULTS: A group of 17 patients (9 primary resistant, 8 relapsed) with AML or advanced myelodysplastic syndrome (MDS) received 20 courses of MTA . The median age of the patients was 55 years (20-70 years) . Two patients (12%) achieved complete remission . The median overall survival was 8.2 weeks . Five patients (29%) developed grade 3/4 hepatic transaminitis, including one patient (6%) who died with hepatic venoocclusive disease . CONCLUSIONS: MTA was moderately effective and associated with significant toxicity in patients with refractory AML. Gen Dent, 2002 Sep-Oct, 50(5), 457 - 63; quiz 464-5 Alveolar osteitis: a review of its etiology, prevention, and treatment modalities; Houston JP et al.; Alveolar osteitis (AO), commonly referred to as dry socket, is by far the most common complication following dental extraction . It represents a breakdown of healing after clot formation but before wound organization . This paper will review the literature associated with the etiology of AO, the risk factors which contribute to AO, and treatment regimens for AO once it is diagnosed . It will conclude with a summary of the current measures that hold the highest promise for the prevention of AO. Pol J Vet Sci, 2002, 5(3), 127 - 30 Pharmacokinetics of tylosin in broiler chickens; Kowalski C et al.; Biological availability and pharmacokinetic properties of tylosin were determined in broiler chickens after oral (p.o.) and intravenous (i.v.) administration at a dose of 10 mg/kg . The calculated bioavailability--F%, by comparing AUC values--p.o . and AUC--i.v., ranged from 30%-34% . After intravenous injection tylosin was rapidly distributed in the organism, showing elimination half-life (t1/2 beta) values of 0.52 h and distribution volume (Vd) of 0.69 L/kg, at a clearance rate (Cl) of 5.30 +/- 0.59 ml/min/kg . After oral administration, tylosin has a similar distribution volume (Vd = 0.85 L/kg), while the elimination half-life t1/2 beta of 2.07 h was four times bigger than after i.v . administration at Cl = 4.40 +/- 0.27 ml/min/kg . The obtained value tmax = 1.5 h for tylosin after oral administration indicates that using this antibiotic with drinking water in broiler chickens is the method of choice . However, a relatively low value Cmax = 1.2 micrograms/ml after oral administration of tylosin shows that dosing of this antibiotic in broiler chickens should be higher than in other food producing animals. Vet Ther, 2002 Fall, 3(3), 290 - 6 Evaluation of the in vitro cytotoxicity of mitoxantrone following repeated freeze-thaw cycles; Mauldin GN et al.; Mitoxantrone, an antineoplastic anthracycline antibiotic with a wide range of veterinary applications, was developed as a less cardiotoxic alternative to doxorubicin, a related compound in this family of chemotherapy agents . Mitoxantrone has not gained widespread acceptance in the veterinary community, primarily due to its cost and single-dose packaging in a volume that exceeds the needs of the majority of veterinary cancer patients . The in vitro cytotoxicity of mitoxantrone following repeated freeze-thaw cycles was evaluated to determine whether long-term storage at -20 degrees C resulted in decreased efficacy . The drug was frozen between treatment cycles to minimize the risk of bacterial contamination because it is supplied as a preservative-free solution . Results indicated mitoxantrone maintained its cytotoxicity against cancer cells in culture following multiple freeze-thaw cycles spanning at least 12 months. Intensive Care Med, 2002 Dec, 28(12), 1708 - 17 Epub 2002 Nov 01. Prevention of severe Candida infections in nonneutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination; Garbino J et al.; OBJECTIVE: Infections caused by Candida spp . are a major cause of morbidity and mortality in critically ill patients and usually develop from endogenous colonization . We assessed the effectiveness of adding fluconazole to a selective digestive decontamination regimen to prevent candidal infections . DESIGN AND SETTING: We performed a prospective, randomized, double-blind, placebo-controlled trial among medical and surgical intensive care unit patients at a large university hospital . PATIENTS: All adult patients mechanically ventilated for at least 48 h with an expectation to remain so for at least an additional 72 h, and receiving selective decontamination of the digestive tract . INTERVENTIONS: Patients were randomly assigned fluconazole 100 mg daily (n=103) or placebo (n=101) . MEASUREMENTS AND RESULTS: Candida infections occurred less frequently in the fluconazole group (5.8%) than in the placebo group (16%; rate ratio 0.35; Cl(95) 0.11-0.94) . Some 90% of candidemia episodes occurred in the placebo group (rate ratio for fluconazole use 0.10; Cl(95) 0.02-0.74) . The rate of treatment failure, development of candidal infection, or increased colonization, was 32% in the fluconazole group and 67% in the placebo group (P<0.001) . Crude in-hospital mortality was similar in the two groups (39% fluconazole vs . 41% placebo) . CONCLUSIONS: Prophylactic use of fluconazole in a selected group of mechanically ventilated patients at high risk for infection reduces the incidence of Candida infections, in particular candidemia. Dis Esophagus, 2002, 15(3), 210 - 3 Treatment of caustic ingestion: an analysis of 239 cases; Mamede RC et al.; The objective of the present study was to analyze a 37-year historical series of patients who had ingested caustic substances, and who were treated in a teaching hospital, to assess the effectiveness of the therapy administered during this period . We studied 239 patients who ingested caustic soda (NaOH) from 1957 to 1994 . Data were collected from the medical records of the patients and from interviews with them and analyzed by software and by statistical tests of association . The results showed that more women than men ingested caustic substances (57%, n=153) . Ingestion was associated with suicidal intent in 60% of cases and was accidental in 37.2% of cases . The amount of substance ingested ranged from a trace to as much as three tablespoons, with the amount tending to be larger in the suicide attempts . Of the 215 patients for whom information about complications due to ingestion was available, 88.4% (190) presented lesions of the esophagus (73% with stenosis), 1% died during the acute phase, and 10.6% did not present complications . The data revealed that the presence and severity of stenosis were correlated with the amount of caustic substance ingested . The treatment received by the patients in the study sample varied over the years according to the prevailing literature recommendations . Based on our review, we conclude that neither the use of an antidote nor early treatment immediately after ingestion is effective . Treatment with a corticosteroid (1.5-2 mg/kg/day prednisone), an antibiotic, and a high-protein and hypercaloric diet seems to be beneficial for patients who ingest small or medium amounts of caustic soda . When 2-3 tablespoons are ingested, corticosteroids, in addition to being unable to prevent the formation of esophageal stenosis, increase the risk of other complications. Phys Ther, 2002 Dec, 82(12), 1224 - 31 Physical therapist management of fluoroquinolone-induced Achilles tendinopathy; Greene BL; BACKGROUND AND PURPOSE: Use of fluoroquinolone antibiotics is reported to be a cause of adverse musculoskeletal effects, such as tendinopathies and tendon ruptures . The purpose of this case report is to describe the management and outcomes of a patient with bilateral Achilles tendinopathy secondary to fluoroquinolone antibiotic use . CASE DESCRIPTION: The patient was a 41-year-old man who developed bilateral Achilles tendon pain on the third day of levofloxacin use . The physical therapy intervention consisted of an initial phase to reduce stress on the tendon through the use of crutches and orthoses and a second phase to progressively stress the tendon through exercise and functional activities . OUTCOMES: After 11 weeks of physical therapy (14 treatments), the patient's pain decreased from 3/10 to 1/10 on a visual analog scale and his Lower Extremity Functional Scale score increased from 28/80 to 71/80 . DISCUSSION: An overlapping 2-phased intervention approach based on connective tissue remodeling principles may be effective in elimination of pain and restoration of function following fluoroquinolone-induced Achilles tendinopathy. Mol Cells, 2002 Oct 31, 14(2), 163 - 7 Molecular design and biological activities of NF-kappaB inhibitors; Umezawa K et al.; NF-kappaB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins . We designed a new NF-kappaB inhibitor that is based on the structe of the antibiotic epoxyquinomicin C . The designed compound, dehydroxymethyl-epoxyquinomicin (DHMEQ), inhibited the TNF-alpha-induced activation of NF-kappaB, and showed an anti-arthritic effect in mice . Recently, we looked into its mechanism of inhibition . DHMEQ inhibited the TNF-alpha-induced cellular DNA binding of nuclear NF-kappaB, but not the phosphorylation or degradation of I-kappaB . Moreover, DHMEQ inhibited the TNF-alpha-induced nuclear accumulation of p65, a component of NF-kappaB . On the other hand, DHMEQ did not inhibit the nuclear transport of Smad2 and the large T antigen . Also, it did not inhibit the TNF-alpha-induced activation of JNK, but synergistically induced apoptosis with TNF-alpha in human T cell leukemia Jurkat cells . Therefore, DHMEQ specifically inhibited the NF-kappaB-activating pathway in the TNF-alpha-treated cells . Taken together, our data show that DHMEQ is a unique inhibitor of NF-kappaB that acts at the level of the nuclear translocation . It may be useful as an anti-inflammatory and anticancer agent. Schweiz Arch Tierheilkd, 2002 Oct, 144(10), 519 - 30 {Health and welfare of dairy cows in different housing programs}; Spycher B et al.; The objective of this study was to evaluate the effect of two Swiss animal welfare friendly housing programs, 'regular access to outdoor facilities' (RAUS) and 'improved loose housing systems' (BTS) on health and welfare of dairy cows . During two years, the following indicators of health and welfare were observed on 136 randomly selected dairy farms: injuries around the joints, callosities, lameness, teat injuries, cleanliness, behaviour during lying and rising, body condition score, and incidence of medical treatments . Farms participating in both housing programs (BTS + RAUS) and farms with the program RAUS were compared to traditional farms that did not participate in a program . Housing system and management practice were recorded as additional factors influencing health and welfare of cows . Cows on farms participating in BTS + RAUS had, on average, fewer injuries around the hocks and fewer callosities at the carpal joints than cows in farms which did not participate in a housing program . Lameness was most frequent in cows of farms without housing program, followed by cows in tie stalls with the program RAUS and cows in loose housing systems with BTS + RAUS . There were fewer antibiotic treatments in farms with BTS + RAUS compared to the other farms. Medicine (Baltimore), 2002 Nov, 81(6), 458 - 65 The evolution of Lemierre syndrome: report of 2 cases and review of the literature; Chirinos JA et al.; Lemierre syndrome (postanginal septicemia) is caused by an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections . A high degree of clinical suspicion is necessary for diagnosis . Fusobacterium necrophorum is the usual etiologic agent . The disease progresses in several steps . The first stage is the primary infection, which is usually a pharyngitis (87.1% of cases) . This is followed by local invasion of the lateral pharyngeal space and IJV septic thrombophlebitis (documented in 71.5% of cases), and finally, the occurrence of metastatic complications (present in 90% of cases at the time of diagnosis) . A sore throat is the most common symptom during the primary infection (82.5% of cases) . During invasion of the lateral pharyngeal space and IJV septic thrombophlebitis, a swollen and/or tender neck is the most common finding (52.2% of patients) and should be considered a red flag in patients with current or recent pharyngitis . The most common site of metastatic infection is the lungs (79.8% of cases) . In contrast to the preantibiotic era, cavitating pneumonia and septic arthritis are now uncommon . Most patients (82.5%) had fever at some stage during the course of the disease . Gastrointestinal complaints such as abdominal pain, nausea, and vomiting were common (49.5% of cases) . An elevated white blood cell count occurred in 75.2% of cases . Hyperbilirubinemia with slight elevation of liver enzyme levels occurred in one-third of patients, but frank jaundice was uncommon, in contrast to its high frequency reported in the preantibiotic era . We conclude that, most likely as a consequence of widespread antibiotic use for pharyngeal infections, the typical course of the disease has changed since Lemierre's original description . The typical triad in our series was: pharyngitis, a tender/swollen neck, and noncavitating pulmonary infiltrates . The previous classical description of severe sepsis with cavitating pneumonia and septic arthritis was not commonly seen in our review . Mortality was low in our series (6.4%), but significant morbidity occurred, which was likely preventable by early diagnosis and treatment . The pathophysiology, natural history, diagnostic methods for internal jugular vein thrombosis, and management are discussed. Medicine (Baltimore), 2002 Nov, 81(6), 443 - 57 Neurologic presentation of Whipple disease: report of 12 cases and review of the literature; Gerard A et al.; We report 12 cases of Whipple disease in patients with prominent neurologic symptoms, along with 122 cases of Whipple disease with nervous system involvement reported in the literature . We analyzed the clinical signs and results of additional examinations in 2 groups: the first group included patients with predominantly but not exclusively neurologic signs, and the second included patients with clinically isolated neurologic presentation of the disease . Whipple disease is a multisystemic infectious disease due to Tropheryma whippelii that may present with prominent or isolated symptoms of either the central or the peripheral nervous system . Recent reports stress the importance of polymerase chain reaction (PCR) analysis of cerebrospinal fluid, magnetic resonance imaging (MRI) during follow-up, and prolonged antibiotic therapy with drugs able to cross the blood-brain barrier . Cerebrospinal fluid should be analyzed repeatedly during follow-up, and treatment should be discontinued only when the results of PCR assay performed on cerebrospinal fluid are negative . Other examinations to be done include searching for gastrointestinal tract involvement with multiple duodenal biopsies and searching for systemic involvement with lymph node biopsies, which should be analyzed with light microscopy, electron microscopy, and PCR . When all examinations are negative, if Whipple disease is suspected and a lesion is found on brain MRI, a stereotactic cerebral biopsy should be performed . Treating Whipple disease with long-term trimethoprim-sulfamethoxazole is usually effective, but the use of third-generation cephalosporins in case of incomplete response deserves further attention. Ann Thorac Surg, 2002 Nov, 74(5), S1754 - 7; discussion S1792-9 Reoperative cryopreserved root and ascending aorta replacement for acute aortic prosthetic valve endocarditis; Lytle BW et al.; BACKGROUND: Prosthetic aortic valve endocarditis (PVE) is an important complication of aortic valve replacement (AVR) and is a particularly difficult situation after an operation combining AVR with ascending aortic replacement . METHODS: From 1988 through 2000, 27 patients with aortic valve PVE after previous ascending aortic replacement (aortic root replacement in 13, aortic valve replacement with a supracoronary graft in 14) underwent reoperation for aortic root replacement with a cryopreserved aortic allograft and prolonged intravenous antibiotic therapy . All patients were considered to have active PVE (25 with positive cultures); root abscess formation was present in 89% and aortoventricular discontinuity in 41% . RESULTS: One patient (3.7%) died in-hospital, and permanent pacemakers were required in 10 patients (37%) . Mean postoperative follow-up interval was 3.9 +/- 3.0 years, and survival at 1, 2, 5, and 7.5 years was 92%, 88%, 70%, and 56%, respectively . One patient underwent reoperation for recurrent PVE 8 months after operation . CONCLUSIONS: Radical debridement of infected prosthetic material and tissue, and allograft aortic root and ascending aorta replacement, combined with intravenous antibiotic therapy, appears to achieve a low hospital mortality and a high degree of freedom from recurrent infection for patients with PVE after AVR and ascending aortic replacement. Nippon Rinsho, 2002 Nov, 60(11), 2097 - 102 {Compromised host}; Igarashi H et al.; The number of immunocompromised host has been increasing recently . In this article, the defect of host-defence system, immune system and the way to prevent infections in these host were reviewed. J Gene Med, 2002 Nov-Dec, 4(6), 676 - 86 Novel promoter/transactivator configurations for macrolide- and streptogramin-responsive transgene expression in mammalian cells; Weber W et al.; BACKGROUND: The recently developed heterologous macrolide- (E.REX system) and streptogramin- (PIP system) responsive gene regulation systems show significant differences in their regulation performance in diverse cell lines . METHODS: In order to provide optimal regulation modalities for a wide variety of mammalian cell lines, we have performed a detailed analysis of E.REX and PIP systems modified in (i) the transactivation domains of the antibiotic-dependent transactivators, (ii) the type of minimal promoter used, and (iii) the spacing between the operator module and the minimal promoter . RESULTS: These novel E.REX and PIP regulation components showed not only dramatically improved regulation performance in some cell types, but also enabled their use in cell lines which had previously been inaccessible to regulated transgene expression . CONCLUSIONS: Due to their modular set-up the novel E.REX and PIP regulation systems presented here are most versatile and ready for future upgrades using different cell-specific key regulation components . Eur Radiol, 2002 Dec, 12(12), 2973 - 6 Epub 2001 Dec 21. Syphilitic myelitis with diffuse spinal cord abnormality on MR imaging; Tsui EY et al.; Syphilitic myelitis is a very rare manifestation of neurosyphilis . The MRI appearance of syphilitic myelitis is not well documented and only a few cases have been reported . We present a 52-year-old woman with acute onset of paraplegia . Magnetic resonance imaging of the spine showed diffuse high signal intensity in the whole spinal cord on T2-weighted images . Focal enhancement was observed in the dorsal aspect of the thoracic cord on T1-weighted gadolinium-enhanced images . To our knowledge, diffuse spinal cord abnormality in syphilitic myelitis has not been reported in the international literature . Disappearance of the diffuse high-signal lesions with residual focal enhancement was noted after antibiotic therapy . The patient suffered significant neurological deficit despite improvement in the MR images . In this article we present the imaging findings and review the literature of this rare condition. Am J Obstet Gynecol, 2002 Nov, 187(5), 1143 - 6 An aggressive interventional protocol for early midtrimester premature rupture of the membranes using gelatin sponge for cervical plugging; O'Brien JM et al.; OBJECTIVE: This study was performed to evaluate a protocol for treatment of previable premature rupture of membranes (PROM) that includes the administration of gelatin sponge to retard the loss of fluid from the amniotic cavity . STUDY DESIGN: Women with PROM at <or=21 weeks' gestation with a structurally normal singleton; having no evidence of infection, active bleeding, or labor; and a maximum vertical fluid pocket of less than 1.5 cm were candidates . Interventions included hospital admission, amnioinfusion, cervical cerclage, administration of gelatin sponge (Gelfoam) into the amniotic cavity, antibiotic administration, and perioperative tocolysis . Weekly assessment of fluid status was performed and if oligohydramnios returned, patients were offered repeat amnioinfusion . RESULTS: Fifteen women with PROM at 17.9 +/- 2.2 weeks' gestation (range 13-21 weeks) underwent this protocol . Spontaneous PROM was diagnosed in 14 patients and one had iatrogenic PROM after fetoscopy . Eight fetuses reached a viable gestational age (>or=24 weeks, 53%), with six of these newborn infants surviving to hospital discharge (30%) and two suffering intrauterine death . The average gestational age of delivery for survivors was 31.8 +/- 4.3 weeks, range 25 to 36 weeks . Talipes equivarus was observed in three survivors (50%) . Bilateral hip dysplasia and torticollis were also diagnosed in two infants . Respiratory distress syndrome was diagnosed in all cases delivered at less than 32 weeks but was not observed thereafter . No adverse sequelae have been attributed to gelatin sponge exposure . CONCLUSION: The observed survival rate with this interventional approach in a population at highest risk for pregnancy loss justifies further study of this treatment strategy . This protocol may not reduce the rate of musculoskeletal abnormalities. Clin Orthop, 2002 Nov, (404), 132 - 8 Comparison of a static with a mobile spacer in total knee infection; Emerson RH Jr et al.; Patients with infections of a total knee arthroplasty were stratified by medical status . Twenty-six knees in 26 patients treated with a static antibiotic-impregnated polymethylmethacrylate block spacer before 1995 were compared with 22 knees in 22 patients treated after 1995 with a mobile articulating spacer . Both groups were treated with 6 weeks of parenteral antibiotics and had reimplantation within 6 to 12 weeks after placement of the spacer . Followup for the patients who had block spacers was an average 7.5 years (range, 2.8-12.7 years), and followup for the patients with a mobile spacer was an average of 3.8 years (range, 2.6-6.4 years) . Results showed that the patients with the mobile spacers had significantly better average range of motion at followup compared with patients who had block spacers (107.8 degrees compared with 93.7 degrees ) . The reinfection rate was the same between the two groups at 36 months, 7.6% (two of 26) for the patients with block spacers and 9% (two of 22) for the patients with mobile spacers . Extended followup available for the patients who had block spacers revealed a late reinfection rate of 23% (six of 26) with a new organism . There was no difference in the reinfection rate, with new or old organisms, in healthy hosts compared with patients with as many as two medical problems. Eur J Gastroenterol Hepatol, 2002 Nov, 14(11), 1275 - 7 Vanishing bile duct syndrome associated with elevated pancreatic enzymes after short-term administration of amoxicillin; Schwarze C et al.; Amoxicillin is a widely used antibiotic, rarely being considered a cause of hepatic injury . We report the case of a 45-year-old woman who developed a vanishing bile duct syndrome 8 weeks after initiation of amoxicillin therapy . Liver biopsy showed destruction and loss of preformed bile ducts together with an inflammatory infiltrate involving eosinophilic leucocytes . Cholestasis was progressive despite prednisolone treatment and was accompanied by elevation of pancreatic enzymes . The patient died after 18 months from progressive liver failure . This case illustrates that amoxicillin alone can be a cause of progressive and ultimately fatal vanishing bile duct syndrome. Semin Dial, 2002 Nov-Dec, 15(6), 418 - 21 Treatment of peritonitis in APD: pharmacokinetic principles; Manley HJ et al.; Clinicians treating peritoneal dialysis (PD)-associated peritonitis should be aware that continuous ambulatory PD (CAPD) and automated PD (APD) have different effects on the pharmacokinetics of antibiotics . Results from various APD and comparative CAPD pharmacokinetic studies are reviewed . In APD patients, antibiotic half-lives were shorter during the cycler exchanges . Antibiotic peritoneal clearance was greater in patients treated with APD than those treated with CAPD regimens . Antibiotic clearance depends upon residual renal function and dialysate flow rate . To ensure that maximal antibiotic bioavailability occurs with intermittent intraperitoneal (IP) dosing, it is recommended that the antibiotic-containing dialysate must dwell at least 4 hours to ensure an adequate antibiotic depot in the body . Knowledge of antibiotic disposition in PD patients will assist clinicians in appropriate IP antibiotic dose selection and prevention of dose-related adverse effects. Arch Intern Med, 2002 Nov 25, 162(21), 2437 - 42 Interhospital differences in nosocomial infection rates: importance of case-mix adjustment; Sax H et al.; BACKGROUND: Nosocomial infection rates are used to assess patient safety and the effectiveness of health care systems, but adjustment for case-mix, a key factor for benchmarking, is often overlooked . OBJECTIVES: To perform a nationwide prevalence study of nosocomial infection and evaluate the impact of hospital size on infection rates . METHODS: One-week-period prevalence study in 18 acute care hospitals ranging from small primary to large tertiary care institutions . All adult inpatients in medical, surgical, and intensive care units hospitalized at time of study were included . Infection prevalence and case-mix determinants were calculated according to hospital size . After each factor was tested for its significance on the occurrence of nosocomial infection, all factors were introduced in a multivariate model with hospital size as the main explanatory variable and nosocomial infection as the dependent variable . RESULTS: Among 4252 patients, 429 developed 470 nosocomial infections, for an overall prevalence of 10.1% (intensive care units, 29.7%; medical, 9.3%; surgical, 9.2%; and mixed wards, 14.1%) . Unadjusted prevalence rates were 6.1% in small, 10.0% in intermediate, and 10.9% in large hospitals (P =.007) . Increased comorbidity (odds ratio, 1.80), cancer (1.68), trauma (1.75), neutropenia (4.66), antibiotic exposure (6.64), history of intensive care unit stay (2.14), referral from another hospital (1.87), intubation for 24 hours or more (2.09), and prolonged stay (3.35) were independently associated with nosocomial infection (all P<.05), but hospital size was not . CONCLUSIONS: Higher infection rates observed in larger hospitals were partly associated with unfavorable case mix . Unadjusted rates may lead to erroneous assumptions for health care prioritization. Mikrobiol Z, 2002 Jul-Aug, 64(4), 19 - 23 {Spontaneous and induced variability of Streptomyces aureofaciens--chlortetracycline producer}; Stryzhkova HM et al.; Spontaneous and induced variability of Streptomyces aureofaciens strain T{symbol: see text} 633 {symbol: see text} and its variants has been investigated . Correlative relation between the antibiotic formation and colonies morphology was observed . Combined effect of nitrosoguanidine and UV-beams resulted in the obtaining of 27 variants which exceeded activity of strain T{symbol: see text} 633 {symbol: see text} by 30-35% and were stable as to antibiotic biosynthesis during 7-10 generations. Eur J Med Res, 2002 Sep 30, 7(9), 399 - 403 The two-stage concept with temporary subcutaneous implantation of a vacuum sealing system: an alternative surgical approach in infected partial abdominal defects after lapratomy or abdominoplasty; Cedidi C et al.; BACKGROUND: Infected abdominal defects after laparatomy or abdominoplasty may present serious complications . The management of a progressive infection in the abdominal region with partial necrosis -without peritoneal irritation - is treated variously . Multiple revisions due to re-infection or seroma are often necessary . The different surgical treatment options almost always necessitate an extended immobilisation and hospitalisation of the patient . PATIENTS AND METHODS: In five patients with infected partial abdominal defects after abdominoplasty (n = 3) or laparatomy (n = 2) successful management of infection was achieved in a two stages with temporary subcutaneous implantation of a polyurethane foam, combined with a vacuum assisted wound closure device, followed by secondary wound closure . In the first step a debridement, subcutaneous implantation of the foam, combined with intermittent subathmospheric pressure through a V.A.C . device was performed . In the second step an explantation of the foam, re-debridement and secondary wound closure was possible over 2 - 4 drains . RESULTS: In all patients - after a temporary immobilisation of 5 days, and systemic antibiotic administration - wound healing was achieved . In one diabetic patient another single revision was necessary, because of the necrosis of a distal wound edge . The mean hospitalisation after application of these procedures was 15 days (12 - 19) . CONCLUSIONS: The surgical treatment of infected partial abdominal defects after laparatomy or abdominoplasty - performed in a two-stage procedure with temporary subcutaneous implantation of a V.A.C.-system, and secondary wound closure, offers a high level of safety, and presents an useful alternative tool in the difficult management of these patients. Clin J Oncol Nurs, 2002 Nov-Dec, 6(6), 323 - 31 Systemic Candida infections in patients with leukemia: an overview of drug therapy; Blash JL; Systemic fungal infections are becoming increasingly common in patients with hematologic malignancies receiving antineoplastic therapy . The presence of acute myeloid or acute lymphoid leukemia, plus the use of chemotherapy to totally ablate malignant bone marrow cells, puts patients in a protracted neutropenic state . During this profound and prolonged neutropenic phase, patients receive antibiotic therapy for suspected or identified bacterial infections . However, when fever or other signs of infection continue despite antibiotic therapy, patients frequently need to be treated for suspected or identified systemic fungal infections . These infections may occur in patients receiving either standard antileukemia therapy or research protocol therapy involving new drugs, new drug combinations, higher doses, or newer schedules of established drugs . After antifungal therapy is initiated, it may be continued postdischarge in outpatient or homecare settings . Therefore, becoming knowledgeable about antifungal therapy is important for all oncology nurses regardless of practice setting. J Biol Chem, 2003 Jan 31, 278(5), 3314 - 22 Epub 2002 Nov 13. A dispensable yeast ribosomal protein optimizes peptidyltransferase activity and affects translocation; Dresios J et al.; Yeast ribosomal protein L41 is dispensable in the yeast . Its absence had no effect on polyphenylalanine synthesis activity, and a limited effect on growth, translational accuracy, or the resistance toward the antibiotic paromomycin . Removal of L41 did not affect the 60:40 S ratio, but it reduced the amount of 80 S, suggesting that L41 is involved in ribosomal subunit association . However, the two most important effects of L41 were on peptidyltransferase activity and translocation . Peptidyltransferase activity was measured as a second-order rate constant (k(cat)/K(s)) corresponding to the rate of peptide bond formation; this k(cat)/K(s) was lowered 3-fold to 1.15 min(-1) mm(-1) in the L41 mutant compared with 3.46 min(-1) mm(-1) in the wild type . Translocation was also affected by L41 . Elongation factor 2 (EF2)-dependent (enzymatic) translocation of Ac-Phe-tRNA from the A- to P-site was more efficient in the absence of L41, because 50% translocation was achieved at only 0.004 microm EF2 compared with 0.02 microm for the wild type . Furthermore, the EF2-dependent translocation was inhibited by 50% at 2.5 microm of the translocation inhibitor cycloheximide in the L41 mutant compared with 1.2 microm in the wild type . Finally, the rate of EF2-independent (spontaneous) translocation was increased in the absence of L41. Dis Colon Rectum, 2002 Nov, 45(11), 1528 - 34 Indeterminate colitis: the real story; Rudolph WG et al.; PURPOSE: Up to one in five patients undergoing surgery for ulcerative colitis will have ambiguous histology, with features of both ulcerative colitis and Crohn's disease, and are categorized as having indeterminate colitis . We hypothesized that functional outcomes in indeterminate colitis patients undergoing ileal pouch-anal anastomosis are comparable with those of ulcerative colitis patients undergoing ileal pouch-anal anastomosis . METHODS: Physician-conducted interviews of 120 consecutive ileal pouch-anal anastomosis patients with a preoperative diagnosis of ulcerative colitis were reviewed, with a mean follow-up of 54 months . All colectomy specimens were reviewed by a single pathologist . Any changes in histologic diagnosis from ulcerative colitis to indeterminate colitis or Crohn's disease, frequency of postoperative complications, pouch function, and long-term postoperative medication usage were recorded . RESULTS: Although postoperative fistulas were more common in indeterminate colitis than ulcerative colitis (26 vs . 10 percent; P = 0.02, chi-squared), no indeterminate colitis patient required a permanent ileostomy as compared with six ulcerative colitis patients . Long-term functional results were similar . Overall, two-thirds of patients developed pouchitis . Ulcerative colitis and Crohn's disease patients were more likely to have had >3 episodes of pouchitis (58 and 72 percent) compared with indeterminate colitis patients (29 percent; P = 0.006, chi-squared) . A greater number of Crohn's disease patients required maintenance oral antibiotic therapy (64 percent) to achieve satisfactory functional results compared with both indeterminate colitis and ulcerative colitis patients (20 and 28 percent; P = 0.014, chi-squared) . CONCLUSIONS: Although ileal pouch-anal anastomosis patients with indeterminate colitis have more postoperative fistulas, long-term function is equal to that of ulcerative colitis patients and better than Crohn's disease patients . Ileal pouch-anal anastomosis should be offered to patients with indeterminate colitis and those with severe colitis in whom clear differentiation between indeterminate colitis and ulcerative colitis cannot be made. Public Health Rep, 2002 May-Jun, 117(3), 233 - 51; discussion 231-2 Effect of race and/or ethnicity in use of antiretrovirals and prophylaxis for opportunistic infection: a review of the literature; Palacio H et al.; OBJECTIVE: The authors performed a systematic and critical review of published studies investigating potential associations between race and/or ethnicity and use of HIV-related medications, including antiretroviral medications and medications used for prophylaxis of opportunistic infections . METHODS: The authors conducted a Web-based search of the University of California MEDLINE/HealthSTAR database for articles published from January 1, 1985, to October 31, 2001 . References cited in articles were used to identify potential additional articles for this review . The authors reviewed articles published in peer-reviewed scientific journals that analyzed race/ethnicity as a predictor of antiretroviral or HIV-related prophylactic medication use . RESULTS: The authors identified 28 reports, including: (a) 26 studies published in 1991-2001 that addressed antiretroviral use, spanning data collection periods from 1984 to 1999; (b) 11 studies published in 1994-2001 that addressed prophylaxis for Pneumocystis carinii pneumonia (PCP), reporting on data collected from 1989 to 1998; and (c) three studies published from 1998 to 2001 that addressed prophylaxis for other opportunistic infections, reporting on data collected from 1993 to 1998 . Among the studies that addressed antiretroviral use, 14 found a negative association between non-white race and at least one measure of antiretroviral use, three studies found a positive association, and 16 studies found no association; seven studies found mixed results across several measures of antiretroviral use . Only four of 11 studies found a negative association between race/ethnicity and PCP prophylaxis; the remainder found no association . Two out of three studies found a negative association between race/ethnicity and prophylaxis for other infections . CONCLUSIONS: There is evidence of racial/ethnic disparities in utilization of antiretrovirals, which are known to be strongly associated with positive HIV health outcomes . It is now imperative for researchers and policy makers to better understand the causes of these disparities, evaluate programs that affect the delivery of HIV medications, and implement program and policy changes necessary to address the disparities. N Engl J Med, 2002 Nov 14, 347(20), 1549 - 56 Dexamethasone in adults with bacterial meningitis; de Gans J et al.; BACKGROUND: Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis . In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects . METHODS: We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis . Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days . The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs . a score of 1 to 4, indicating an unfavorable outcome) . A subgroup analysis according to the causative organism was performed . Analyses were performed on an intention-to-treat basis . RESULTS: A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group . The base-line characteristics of the two groups were similar . Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03) . Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04) . Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006) . Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group . CONCLUSIONS: Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding . Biochim Biophys Acta, 2002 Dec 16, 1593(1), 77 - 84 Involvement of HMGB1 and HMGB2 proteins in exogenous DNA integration reaction into the genome of HeLa S3 cells; Ueda T et al.; High mobility group 1 and 2 proteins (HMGB1 and HMGB2) are abundant chromosomal proteins in eukaryotic cells . We examined the involvement of HMGB1 and HMGB2 in nonhomologous illegitimate recombination . The HMGB1 or HMGB2 expression plasmid, carrying the neo(r) gene as a selection marker, was introduced into HeLa S3 cells to obtain stably-transfected cells . The number of G418-resistant colonies was about 10 times the number of colonies of control cells transfected with plasmids not carrying the HMGB genes . The copy number of the stably-integrated neo(r) gene was higher in the cells transfected with the HMGB expression plasmids than in control cells . The exogenous DNA integration was suggested to have occurred by nonhomologous illegitimate recombination . On the contrary, the introduction of the HMGB antisense RNA expression plasmid with a reporter plasmid carrying the neo(r) gene into HeLa S3 cells decreased the number of G418-resistant colonies . These results indicate that HMGB1 and HMGB2 each have a novel function as stimulators of stable integration of plasmid DNA into the host genome and that they may be important for the process of spontaneous DNA integration in living cells . Surv Ophthalmol, 2002 Sep-Oct, 47(5), 500 - 9 The trachoma menace in the United States, 1897-1960; Allen SK et al.; Although largely considered a problem of developing countries today, trachoma was once extremely common in parts of the United States and accounted for a large proportion of blindness . Under an act signed by President Woodrow Wilson in June 1913, a substantial part of the U.S . Public Health Service budget was earmarked to fight trachoma . Numerous trachoma surveys revealed the presence of a "trachoma belt" across the mid United States, and the prevalence of trachoma reached as high as 50-90% among school children on some Indian reservations . Crowding, poverty, and lack of clean water and hygiene were identified as risk factors for trachoma . Measures taken to combat trachoma included isolation schools for infected children, special government trachoma hospitals and field clinics, screening of immigrants to the U.S., improvements in hygiene and sanitation, and antibiotic therapy . The Indian Health Service utilized radical eyelid surgery with reportedly disastrous consequences . Prevalence surveys show a clear decline in trachoma in the U.S . during the twentieth century. Cleve Clin J Med, 2002 Nov, 69(11), 889 - 96 Mitral valve prolapse: old beliefs yield to new knowledge; Hayek E et al.; Much of the conventional wisdom about the prevalance, causes, diagnosis, symptoms, effects, and treament of mitral valve prolapse (MVP) is changing . MVP has a benign course and excellent prognosis for most patients, with only a small minority developing serious complications. Transfusion, 2002 Sep, 42(9), 1114 - 22 A prospective, randomized clinical trial of universal WBC reduction; Dzik WH et al.; BACKGROUND: Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients . Whether or not WBC reduction should be universally applied is highly controversial . STUDY DESIGN AND METHODS: In a general hospital, a randomized, controlled clinical trial of conversion to universal WBC reduction was conducted . Patients (11%) with established medical indications for WBC-reduced blood were not eligible . All other patients who required transfusion were assigned at random to receive either unmodified blood components or stored WBC-reduced RBCs and platelets . Analysis for each patient was restricted to the first hospitalization . RESULTS: All eligible patients (n = 2780) were enrolled . Three specified primary outcome measures were not different between the two groups: 1) in-hospital mortality (8.5% control; 9.0% WBC-reduced; OR, 0.94 {95% CI, 0.72-1.22}; p = 0.64); 2) hospital length of stay (LOS) after transfusion (median number of days, 6.4 for control and 6.3 for WBC-reduced; p = 0.21); and 3) total hospital costs (median, $19,500 for control and $19,200 for WBC-reduced, p = 0.24) . Secondary outcomes (intensive care LOS, postoperative LOS, antibiotic usage, and readmission rate) were not different between the two groups . Subgroup analysis based on patient age, sex, amount of blood transfused, or category of surgical procedure showed no effect of WBC reduction . Patients who received WBC-reduced blood had a lower incidence of febrile reactions (p = 0.06) . CONCLUSION: A beneficial effect of conversion from selective to universal WBC reduction was