Ceylon Med J, 1996 Jun, 41(2), 51 - 4 Primary drug resistant tuberculosis in the Central Chest Clinic, Colombo; Perera J et al.; OBJECTIVE: To determine the drug sensitivity of Mycobacterium tuberculosis strains isolated from pretreatment (primary) cases of pulmonary tuberculosis . DESIGN: A descriptive study . SETTING: The Central Chest Clinic, Colombo . PATIENTS: 103 patients with pulmonary tuberculosis who have not taken anti-tuberculosis drugs previously . MEASUREMENTS: Antibiotic sensitivity pattern of M tuberculosis isolates for isoniazid (INAH), ethambutol (EMB), rifampicin (RMP) and streptomycin (SM) tested in drug incorporated Lowenstein Jenson (LJ) medium using resistance ratio method . RESULTS: 15.5% isolates of M tuberculosis were resistant to at least one drug . Resistance to a single drug was found to be most prevalent (69%) among the resistant isolates and among these INAH resistance was most prevalent followed by streptomycin . None of the isolates were resistant to all four drugs . Resistance rates to individual drugs were INAH 9.7% . SM 6.7% EMB 2.9% and RMP 2.9% . CONCLUSIONS: Since the introduction of RMP and EMB in the treatment regimens from mid-1970s the incidence of tuberculosis and rate of primary drug resistance to anti-tuberculosis drugs has not changed significantly (p > 0.05) when compared with the results of studies conducted previously (2, 3) . However, it is recommended that regular surveillance of drug sensitivity pattern should be maintained to determine alternate drug regimes and to detect the spread of resistant strains in the community. Anasthesiol Intensivmed Notfallmed Schmerzther, 1996 Jun, 31(5), 318 - 20 {Postoperative mediastinal and subcutaneous emphysema after intubation narcosis}; Obenhaus T; The case of a 16-year old female is presented who underwent laparoscopy under general anaesthesia and uncomplicated endotracheal intubation . Four hours after uneventful anaesthesia and extubation the patient started vomiting and coughing . Subcutaneous tissue emphysema developed and pneumomediastinum was diagnosed on a chest roentgenogram . A small lesion in the posterior wall of the trachea and consequent upon intubation by indirect tracheoscopy was identified as the possible source of air entry on the third postoperative day . Air accumulation and tracheal lesion protractedly responded to antitussive and antibiotic medication . A tracheal lesion during intubation is the most frequent and thus the most probable cause of air accumulation presenting as pneumomediastinum, pneumothorax or subcutaneous emphysema . As in the present case, increased airway pressure from vomiting or coughing even after a latent period may induce the phenomenon . Very occasional reports on spontaneous pneumomediastinum in young individuals must not detract the circumstances of endotracheal intubation from suspecting an iatrogenic lesion, confirming it by immediate endoscopy and thereupon deciding on conservative or surgical treatment. Orthopade, 1996 Jun, 25(3), 223 - 33 {Intramedullary nailing of open fractures}; Krettek C et al.; The goal of treatment of open fractures is to prevent infection, promote fracture healing, and restore normal limb alignment and function . The initial treatment of these fractures includes: debridement, soft tissue coverage, antibiotic therapy, and fracture stabilization . Four different techniques for intramedullary nailing for the fixation of open fractures have been employed: (1) unreamed, unlocked nails (i.e., Ender and Lottes, which have low infection rates, but are mechanically insufficient); (2) reamed unlocked nailing (which relies on overreaming to provide stability through bone-nail surface contact, but is associated with high infection rates); (3) reamed locked nailing (which may rely on limited reaming because of the interlocking screws); and (4) unreamed nailing (which always relies on interlocking screws and is associated with function better than and infection rates similar to those with external fixation, but has an increased incidence of screw breakage) . In contrast to the biological problems in the tibia, those problems encountered in the femur are more predominantly mechanical in origin . For humeral shaft fractures, shoulder problems associated with the antegrade approach are frequent, and bypassing the rotator cuff with a retrograde approach appears advantageous. Antimicrob Agents Chemother, 1996 Jun, 40(6), 1352 - 9 Paradoxical effect of clindamycin in experimental, acute toxoplasmosis in cats; Davidson MG et al.; Cats were experimentally inoculated parenterally with the ME49 strain of Toxoplasma gondii to characterize the efficacies of two different dosages of orally administered clindamycin hydrochloride in the treatment of ocular toxoplasmosis . Concentrations of clindamycin hydrochloride at levels previously suggested to be inhibitory to T . gondii replication in vitro were achieved in the serum and aqueous humor but not in the cerebrospinal fluid . Antibiotic therapy, initiated 7 days after inoculation, resulted in no significant difference in the morphometric severity of ocular posterior segment lesions compared with that in the control groups . Treatment appeared to blunt T . gondii-specific immunoglobulin M production but had no significant effect on immunoglobulin G titers . Paradoxically, clindamycin administration was associated with increased morbidity and mortality from hepatitis and interstitial pneumonia, which are characteristic of generalized toxoplasmosis . Serum tumor necrosis factor alpha activity was detected at moderate levels in all groups of cats and correlated with the severity of clinical disease . The results of the study suggest that clindamycin, when administered at this specific time interval following inoculation, does not ameliorate ocular lesions and has a detrimental effect on the clinical course of acute, experimental toxoplasmosis in cats . The factors responsible for and the relevance of this detrimental effect to naturally occurring toxoplasmosis in humans and pet cats were not clear from the study but may relate to an antibiotic-associated decrease in the antitoxoplasmic activity of phagocytic cells responsible for the control of T . gondii. Genitourin Med, 1996 Jun, 72(3), 217 - 9 Emergency hormonal contraception usage in genitourinary medicine clinic attenders; Evans JK et al.; OBJECTIVE: To assess the indications for usage of emergency hormonal contraception amongst a population of London genitourinary medicine clinic attenders . METHODS: In a prospective study, 150 consecutive women receiving emergency hormonal contraception (EHC) were enrolled . The attending doctor completed a questionnaire of patient details and prescribed EHC with prophylactic prochlorperazine . Follow-up was arranged three weeks later, at which time outcomes and side-effects of therapy were recorded . For those women who did not reattended as planned case notes were reviewed at three months . RESULTS: Of 150 women surveyed, 100 (66%) reported contraceptive method failure, 48 (32%) had used no contraception at the time of last sexual intercourse and two requested EHC after sexual assault . Ninety three (62%) reported condom failure, 7 (5%) oral contraceptive pill failure . Seventy five (50%) had used EHC before (range 1-10 times) . Seventy one (47%) women reattended within three months . Five (3.3%) of the 150 women were pregnant; none of these cases had experienced nausea or vomiting whilst taking EHC . Side-effects were reported by 22 (31%) of the 71 patients who reattended . Nine (6%) women had been followed-up in the family planning advisory clinic . Of the 71 women who reattended, 39 (55%) reported that their preferred future method of contraception would be condoms . Of the 150 women 19 (13%) underwent tests for sexually transmissible infections within one month of presentation . CONCLUSIONS: EHC usage in this population was associated with a failure rate of at least 3.3% and an overall side effect rate of 31% . Despite requests for emergency contraception because of condom failure many elected to continue using condoms as their preferred method of contraception . The majority of women (53%) did not return for follow-up or family planning advice, and so we believe that future contraceptive plans must be addressed at the time EHC is prescribedPIP: In England, health providers conducted a prospective study of 150 consecutive women 14-43 years old who sought emergency hormonal contraception (EHC) (50 mcg ethinyl estradiol + 500 mcg norgestrel) at the genitourinary medicine clinic of The Royal London Hospital in the Whitechapel section of London . 50% had also used EHC in the past . 23% had experienced at least 1 induced abortion . The reasons for EHC use were contraceptive failure for 100 (66%) women, unprotected sexual intercourse for 48 (32%) women, and rape for 2 women . 93% of the women reporting contraceptive failure were using a condom during the index sexual intercourse . The remaining women recognized the possibility of failure of their oral contraceptives (e.g., concurrent use of an antibiotic and forgotten pill) . 50 (33%) and 21 (14%) women returned to the clinic for follow-up within 1 month and 1-3 months of initial presentation, respectively . Nine of these women had attended the family planning advisory clinic . 3.3% of the 71 women who returned to the clinic were pregnant . 22 (31%) of the women who returned to the clinic reported side effects (10 nausea and vomiting, 9 nausea, 5 abdominal pain, 1 breast tenderness, and 1 a panic attack) . More than 31% of returning women reported an abnormal period after using EHC . 51% of returning women said that their preferred future method of contraception would be condoms . 10% either had not yet decided to use contraception or were planning to become pregnant . Clinic staff screened only 13% of all 150 women for sexually transmitted diseases (STDs) within 1 month of unprotected intercourse . None of them had an STD . Six of the 150 women returned for a second EHC prescription within 3 months . These findings indicate the need for clinicians to address future contraceptive plans at the time of EHC prescription, since most women did not return for follow-up or family planning advice . They should also screen for STDs during this initial contact considering the high rate of unprotected intercourse . J Am Podiatr Med Assoc, 1996 Jun, 86(6), 275 - 9 "Stand down for the homeless" . Podiatric screening of a homeless population in Cleveland; Robbins JM et al.; Health care for the homeless is a major public health concern . With the rise in antibiotic-resistant tuberculosis, the increase of human immunodeficiency virus (HIV) diseases, and other health risks, the medical community has begun to recognize the urgency of taking a proactive role in providing care for this population . Lower extremity pathology can result in limb-threatening and, in some cases, life-threatening sequelae for homeless populations . This patient group has limited access to regular hygiene, appropriate shoes, and podiatric medical care . Participation in the "Stand Down for the Homeless" projects provided an opportunity to evaluate the podiatric needs of a homeless population and to project a response to those needs . The authors define and compare this homeless population with the national homeless population, compare the podiatric needs of this homeless populations versus the general population, and respond to those needs. Am J Respir Crit Care Med, 1996 Jun, 153(6 Pt 1), 1914 - 7 Aerosolized recombinant human DNase in hospitalized cystic fibrosis patients with acute pulmonary exacerbations; Wilmott RW et al.; The goal of this study was to evaluate the safety and efficacy of recombinant human DNase (rhDNase) in hospitalized patients with cystic fibrosis (CF) experiencing acute pulmonary exacerbations . Eighty patients with documented CF were enrolled at 11 CF centers when admitted for antibiotic therapy . Patients were at least 5 yr old with a forced vital capacity (FVC) > or = 35% of predicted and an oxygen saturation > or = 90% on a fraction of inspired oxygen (FIO2) < 0.5 . Patients were randomized to receive rhDNase 2.5 mg in 2.5 ml excipient twice a day (n = 43) or 2.5 ml excipient alone twice daily (n = 37) along with conventional treatment for exacerbations . Administration of rhDNase was not associated with acute adverse events or deaths, and no patients experienced allergic or anaphylactic reactions . Although forced expiratory volume in one second (FEV1) and FVC improved in both treatment groups during the double-blind period, there were no statistically significant differences in the mean change from baseline in FEV1 or FVC between the two groups . rhDNase therapy is safe and well tolerated in CF patients with acute exacerbations requiring hospitalization, but the study did not demonstrate a statistically significant therapeutic effect of rhDNase when added to a regimen of antibiotics and chest physical therapy. J Bacteriol, 1996 Jun, 178(12), 3661 - 3 Genetic analysis of plasmid determinants for microcin J25 production and immunity; Solbiati JO et al.; Microcin J25 (MccJ25) is a small peptide antibiotic produced by an Escherichia coli strain isolated from human feces . The genetic determinants for MccJ25 synthesis and immunity have been cloned from the low-copy-number wild-type plasmid pTUC1OO into the compatible vectors pBR322 and pACYC184 . Physical and phenotypical analysis of insertion mutations and complementation tests defined three contiguous genes involved in MccJ25 production which span a region of about 2.2 kb . Immunity to the antibiotic is provided by an additional gene adjacent to the production region. Dev Med Child Neurol, 1996 Jun, 38(6), 549 - 53 Spinal arteriovenous malformation presenting as meningitis; Lowe DW et al.; An 8-month-old boy presented with a two-day history of lethargy . Meningitis was suspected, and cerebrospinal fluid examination demonstrated pleocytosis and elevated protein . After initial improvement with antibiotic and steroid therapy, progressive lower extremity weakness developed, and a midthoracic spinal cord arteriovenous malformation (AVM) was diagnosed . These lesions present rarely in infancy; the classification and pathophysiology of spinal cord AVMs are reviewed. Plast Reconstr Surg, 1996 Jun, 97(7), 1416 - 9 Research on soft-tissue expander permeability to metronidazole and procaine; Zhan W et al.; This in vitro study was designed to determine if in fact silicone expanders are readily permeable to metronidazole and procaine . The expanders were filled with 0.2% metronidazole or 2% procaine through the filler valves and then immersed wholly in normal saline . At several intervals over 120 hours, a certain amount of the surrounding saline was sampled and the drug levels subsequently determined . In this study, the silicone expanders were indeed readily permeable to the drugs, as measured with an ultraviolet spectrophotometer . A consistent diffusion curve was demonstrated . The rate of diffusion of a drug is inversely proportional to its molecular weight; i.e., the smaller the given drug's molecular weight, the greater is its ability to permeate an expander . In view of this, in the course of expansion, 0.2% metronidazole could be used in clinical expansion instead of normal saline, and a certain amount of antibiotic would diffuse out of the expander to prevent and control the infection. Mayo Clin Proc, 1996 Jun, 71(6), 552 - 5 Postsurgical changes of the breast that mimic inflammatory breast carcinoma; Loprinzi CL et al.; OBJECTIVE: To characterize a clinical syndrome that occurs in some women who have undergone breast or axillary lymph node biopsy or partial mastectomy . MATERIAL AND METHODS: Six case reports are presented, the clinical and histopathologic findings are described, and the implications for recognition of this entity are discussed . RESULTS: Patients who had undergone partial mastectomy, breast biopsy, or axillary lymph node excision shortly thereafter had clinical signs (most notably, erythema and edema) suggestive of infectious mastitis or inflammatory breast cancer . Representative histologic sections of involved skin revealed dilated dermal vessels without specific evidence of infection or cancer . Although antibiotic therapy was generally ineffective, the clinical findings resolved with time (from 2 months to 1 year) . This condition should be considered in the differential diagnosis when this circumscribed patient population has such intervention-related symptoms . CONCLUSION: This clinical syndrome may mimic an infectious or neoplastic process, but we hypothesize that it is due to interruption of lymphatic vessels . Appropriate recognition may alter the use of antibiotic therapy or surgical intervention. Biochem Biophys Res Commun, 1996 May 24, 222(3), 764 - 9 Studies on cooperative binding of an extended distamycin A analogue in the minor groove of DNA by NMR spectroscopy; Yang Y et al.; An analogue of the DNA minor groove binding antibiotic distamycin A, P4+, was found to bind in a 2:1 cooperative manner into the narrow groove of oligodeoxybibonucleotide d(CGTATATACG)2 by 1D-NMR titration . The resulting 2:1 ligand-DNA complex was characterized by 2D NMR experiments including NOESY, COSY, and TOCSY . Two molecules are oriented side by side opposite to each other; each has the N terminus to C terminus direction parallel to the 5' to 3' direction of its adjacent DNA strand . This study corroborates our previous CD and ethidium fluorometry results and provides new support for the generality of the antiparallel side by side binding motif first observed with distamycin A. EMBO J, 1996 May 15, 15(10), 2604 - 11 Enacyloxin IIa, an inhibitor of protein biosynthesis that acts on elongation factor Tu and the ribosome; Cetin R et al.; This work analyzes the action of enacyloxin Ila, an inhibitor of bacterial protein biosynthesis . Enacyloxin IIa {IC50 on poly(Phe) synthesis approximately 70 nM} is shown to affect the interaction between elongation factor (EF) Tu and GTP or GDP; in particular, the dissociation of EF-Tu-GTP is strongly retarded, causing the Kd of EF- Tu-GTP to decrease from 500 to 0.7 nM . In its presence, the migration velocity of both GTP- and GDP-bound EF-Tu on native PAGE is increased . The stimulation of EF-Tu-GDP dissociation by EF-Ts is inhibited . EF- Tu-GTP can still form a stable complex with aminoacyl-tRNA (aa-tRNA), but it no longer protects aa-tRNA against spontaneous deacylation, showing that the EF-Tu-GTP orientation with respect to the 3' end of aa-tRNA is modified . However, the EF-Tu-dependent binding of aa-tRNA to the ribosomal A-site is impaired only slightly by the antibiotic and the activity of the peptidyl-transferase center, as determined by puromycin reactivity, is not affected . In contrast, the C-terminal incorporation of Phe into poly(Phe)-tRNA bound to the P-site is inhibited, an effect that is observed if Phe-tRNA is bound to the A-site nonenzymatically as well . Thus, enacyloxin IIa can affect both EF-Tu and the ribosomal A-site directly, inducing an anomalous positioning of aa-tRNA, that inhibits the incorporation of the amino acid into the polypeptide chain . Therefore, it is the first antibiotic found to have a dual specificity targeted to EF-Tu and the ribosome. Transplantation, 1996 May 15, 61(9), 1370 - 6 Early graft loss secondary to massive hemorrhagic necrosis following orthotopic liver transplantation . Evidence for cytokine-mediated univisceral Shwartzman reaction; Burke GW et al.; Massive hemorrhagic necrosis (MHN) of the liver following orthotopic liver transplantation (OLT) occurs infrequently during an otherwise uneventful recovery 1 week after OLT . It is characterized by fever and sudden deterioration of allograft function leading to failure in the absence of vascular thrombosis . The etiology is unknown, although it is usually preceded by some degree of allograft rejection . Between 6 and 8 days after OLT, four patients (out of 150) became febrile, hypotensive, and experienced a rapid rise in transaminases within 48 hr . Two patients had evidence of mild rejection; the other two had moderate to severe acute cellular rejection . All patients were ABO identical, crossmatch negative . Bolus steroids were given followed by OKT3 in the two patients with severe rejection . Although sepsis was suspected, antibiotic therapy did not ameliorate the clinical course . Each patient progressed to MHN with severe centrilobular necrosis and variable portal infiltrate . High levels of interferon-gamma and tumor necrosis factor-alpha occurred prior to the rise in transaminases in each MHN patient (155 +/- 39 pg/ml and 414 +/- 201 pg/ml, respectively) compared with levels in OLT patients with severe rejection (14 +/- 4 pg/ml and 26 +/- 5 pg/ml, respectively, P < 0.05) . These data support the concept of a cytokine-mediated inflammatory response leading to a univisceral Shwartzman reaction in the transplanted liver . Early recognition of this syndrome and retransplantation are critical for survival. Schweiz Med Wochenschr, 1996 May 11, 126(19), 841 - 4 {MALT-type low-grade B-cell lymphomas of the stomach and Helicobacter pylori}; Binek J et al.; From January 1 1994 to March 1 1995 we observed 6 patients with gastric low-grade B-cell lymphoma of MALT type in association with Helicobacter pylori infection . Endoscopically only 3 of the 6 patients presented with pathological findings . All but one patient with metastatic carcinoma received antibiotic therapy for Helicobacter pylori . Follow-up was not possible in one patient who died unexpectedly . In all 4 patients followed-up, eradication of Helicobacter pylori resulted in regression of the malignant lymphoma . During the median follow-up time of 7 months (2-13 months) no relapse of lymphoma was observed . Our results confirm that gastric low-grade B-cell lymphoma of MALT type can regress after eradication of Helicobacter pylori. Tidsskr Nor Laegeforen, 1996 May 10, 116(12), 1449 - 51 {Total hip arthroplasty after femoral neck fractures . Results from the national registry on joint prostheses}; Skeide BI et al.; From September 1987 to January 1994, data on 3,876 total hip arthroplasties performed because of previous hip fracture were collected in the Norwegian arthroplasty register . During the same period, 19,654 patients received total hip arthroplasties because of osteoarthrosis . The results of total hip arthroplasties after an earlier hip fracture were compared with prostheses in patients who were operated on because of primary osteoarthrosis . After five years the cumulative percentage failure was 4.1 in the fracture group and 3.7 in the arthrosis group (p = 0.19) . After adjustment for differences in sex and age distribution in the Cox model, the fracture patients were shown to have 1.35 times higher risk of revision when compared with the osteoarthrosis patients (p = 0.008) . The reasons for reoperation differed, however, in the two groups . More of the fracture patients than of the osteoarthrosis patients had to be reoperated because of dislocation or femoral shaft fracture, while fewer needed reoperation because the acetabular component had loosened. Biochemistry, 1996 May 7, 35(18), 5684 - 95 Specificity for the exchange of phospholipids through polymyxin B mediated intermembrane molecular contacts; Cajal Y et al.; Structural specificity for the direct vesicle-vesicle exchange of phospholipids through stable molecular contacts formed by the antibiotic polymyxin B (PxB) is characterized by kinetic and spectroscopic methods . As shown elsewhere {Cajal, Y., Rogers, J., Berg, O.G., & Jain, M . inverted question markK . (1996) Biochemistry 35, 299-308}, intermembrane molecular contacts between anionic vesicles are formed by a small number of PxB molecules, which suggests that a stoichiometric complex may be responsible for the exchange of phospholipids . Larger clusters containing several vesicles are formed where each vesicle can make multiple contacts if sterically allowed . In this paper we show that the overall process can be dissected into three functional steps: binding of PxB to vesicles, formation of stable vesicle-vesicle contacts, and exchange of phospholipids . Polycationic PxB binds to anionic vesicles . Formation of molecular contacts and exchange of monoanionic phospholipids through PxB contacts does not depend on the chain length of the phospholipid . Only monoanionic phospholipids (with methanol, serine, glycol, butanol, or phosphatidylglycerol as the second phosphodiester substituent in the head group) exchange through these contacts, whereas dianionic phosphatidic acid does not . Selectivity for the exchange was also determined with covesicles of phosphatidylmethanol and other phospholipids . PxB does not bind to vesicles of zwitterionic phosphatidylcholine, and its exchange of covesicles is not mediated by PxB . Vesicles of dianionic phospholipids, like phosphatidic acid, bind PxB; however, this phospholipid does not exchange . The structural features of the contacts are characterized by the spectroscopic and chemical properties of PxB at the interface . PxB in intermembrane contacts is readily accessible from the aqueous phase to quenchers and reagents that modify amino groups . Results show that PxB at the interface can exist in two forms depending on the lipid/PxB ratio . Additional studies show that the stable PxB-mediated vesicle-vesicle contacts may be structurally and functionally distinct from "stalks", the putative transient intermediate for membrane fusion . The phenomenon of selective exchange of phospholipids through peptide-mediated contacts could serve as a prototype for intermembrane targeting and sorting of phospholipids during their biosynthesis trafficking in different compartments of a cell . The protocols and results described here also extend the syllogistic foundation in interfacial equilibria and catalysis. J Appl Bacteriol, 1996 May, 80(5), 545 - 50 Morphogenesis, ATP content and oxytetracycline production by Streptomyces rimosus in solid substrate cultivation; Yang SS et al.; On agar plates, mycelia of Streptomyces rimosus TM-55 had a slender and smooth surface at 24 h, developed a shorter form and rough surface at 116 h, and lysed after 504 h incubation . Oxytetracycline potency reached a maximum at 94 h . During cultivation on solid substrate, mycelia rarely occurred on the surface at 24 h . The organism appeared as short rods at 166 h, and formed spores at 504 h . The ATP content was maximal at 166 h, while energy charge varied between 0.63 and 0.77 during cultivation . The oxytetracycline potency was maximal at 166 h and each gram of substrate produced 11 mg of antibiotic . ATP content and energy charge of mycelia showed a positive correlation with cell activity and oxytetracycline production. Todays Surg Nurse, 1996 May-Jun, 18(3), 21 - 3 Emerging infectious diseases: threats to the OR? . Interview by Kimberly Howell; Bruning LM; More than 70% of bacterial pathogens in U.S . hospitals are resistant to at least one antibiotic . The problem with emerging infectious diseases is the number of unknown factors . Awareness, surveillance, and strict infection control measures are necessary to combat these threats. Z Geburtshilfe Neonatol, 1996 May-Jun, 200(3), 82 - 7 {Total surgical cervical occlusion . Conclusions from data of several clinica, which use total surgical cervical occlusion}; Saling E et al.; Operative Total Cervix Occlusion (TCO), and in particular early TCO (ETCO), which we introduced in 1980, continues to be an important part of the prematurity prevention program . We were therefore especially interested in obtaining not only a general idea of where, on what scale and with what results TCO is being performed, but also information on the operative technique used, the complication rate associated with it, and preoperative procedure . From the data of the 11 departments which participated in this inquiry it was established that the overall success rate of all TCO procedures performed was over 80% (659 out of 819) . TCO thus enabled to substantially increase the number of infants who survived . This result is also reflected in a comparison of the pregnancies preceding and following TCO . The infant survival rate was increased from below 21% to over 74% . One surprising result was that late occlusion was performed more frequently than early occlusion at more than 50% of the clinics participating in the inquiry . This is presumably due to difficulties in defining early and late occlusion in retrospective data evaluation, and probably also explains why, based on our experience, the success rate with late occlusions was too high . Two occlusions were performed in 43 patients and three or more in 9 (including current TCO) . With 14 cases (1.7%) identified the rate of complications associated with TCO is very low. Minerva Ginecol, 1996 May, 48(5), 181 - 91 {Vaginal and abdominal hysterectomy: comparison and perspectives . Apropos of 385 consecutive cases}; Del Frate G et al.; Hysterectomy is the most common non-pregnancy related surgical procedure . However, given the lack of final guidelines on indications, alternative therapies, surgical approach and outcomes, it is desirable to keep its use under constant monitoring . We reviewed 385 hysterectomies for benign conditions-divided according to surgical approach-performed in the Gynaecological Department of San Daniele del Friuli (Udine-Italy) in 1991-1993, and with one-year follow-up . Traditional approaches, i.e . abdominal (39.2%) and vaginal (60.2%), were used . Colporraphy was performed in 79 cases (33.8% of vaginal hysterectomies); 73.4% of colporraphies were followed by urethral suspension . We reviewed population's patterns, indications and surgical outcomes according to Dicker's suggestions . Vaginal hysterectomy with associated colporraphy concerned a population of patients with average age and parity significantly different from patients who underwent simple vaginal or abdominal hysterectomy . These last two groups, on the other hand, have similar characteristics making them comparable . In abdominal hysterectomy and simple vaginal hysterectomy we reported a complication rate respectively of 21.9% and 7.1% . The advantages of simple vaginal hysterectomy include shorter operating time, reduction in antibiotic drugs usage, earlier hospital discharge and quicker recovery, with obvious cost saving . Our experience therefore supports the view that the balance between abdominal and vaginal hysterectomy could safely be shifted in favour of the last one, the advantages of which could then be made available to a larger number of patients. Acta Otorrinolaringol Esp, 1996 May-Jun, 47(3), 247 - 50 {Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis)}; Morillas Blasco PJ et al.; Kikuchi-Fujimoto's disease (histiocytic necrotizing lymphadenitis) is a benign, self-limited disease of unknown cause that often presents with persistently enlarged cervical lymph nodes that are unresponsive to antibiotic therapy . The disease should be considered in the differential diagnosis of cervical lymphadenopaty: viral infection, tuberculosis, hyperplastic lymphadenopathy, and metastatic disease . It can be confused histologically with malignant lymphoma. Acta Otorrinolaringol Esp, 1996 May-Jun, 47(3), 181 - 6 {Pathophysiological basis of aminoglycoside-induced ototoxicity}; Alamo C et al.; Recently proposed etiopathological mechanisms of aminoglycoside-induced toxicity were reviewed, including calcium, phosphatidylinositol, Na-K dependent ATPase, and neuronal sites of antibiotic action . Difficulties in evaluating the true clinical incidence of this aminoglycoside-induced ototoxicity and risk factors were analyzed . The relation between new dosing regimens (single daily dose) and ototoxicity are discussed. Head Neck, 1996 May-Jun, 18(3), 295 - 8 Cervical osteomyelitis after percutaneous transtracheal ventilation and tracheotomy; Newlands SD et al.; BACKGROUND . Percutaneous transtracheal ventilation has proven useful in emergent airway management . METHODS . A report of a case is presented . Results . A 42-year-old woman who developed laryngospasm required emergency airway intervention She developed massive subcutaneous emphysema and required emergent cricothyroidotomy which was immediately converted to a tracheotomy . Although she was quickly decanulated, she developed late cervical osteomyelitis which resolved with intravenous antibiotic therapy . CONCLUSIONS . Cervical osteomyelitis has not been previously reported as a complication of percutaneous transtracheal ventilation or tracheotomy Contamination of the deep neck spaces facilitated by pressure dissection of the fascial planes may have led to this complication. Trop Anim Health Prod, 1996 May, 28(2 Suppl), 38S - 43S; discussion 74S-86S Chemotherapy of dermatophilosis--a preliminary study; Aning KG et al.; In view of the unpredictability of results of antibiotic therapy of bovine dermatophilosis and following the report of successful use of 10% formalin administered intravenously at the dosage of 20 ml per 100 kg body weight, a trial was undertaken to evaluate the latter treatment in naturally-occurring dermatophilosis in a group of Friesian crossbred cattle . Group 1 animals were given only 10% formalin . Group 2 received 10% formalin and long-acting oxytetracycline (L/AO) at a dosage of 20 mg per kg body weight and Group 3 animals were given only L/AO . Treatments were repeated at intervals of four days . All animals recovered fully, the formalin only-treated ones after three treatments the L/AO-treated ones after a mean of 2.7 treatments and the combination-treated animals after a mean of 1.5 treatments . One LA/O-treated animal showed relapse after four months . This study is continuing. Ann Vasc Surg, 1996 May, 10(3), 211 - 9 Subfascial endoscopic perforator vein surgery: a preliminary report; Bergan JJ et al.; Although the open Linton subfascial perforator vein interruption operation succeeded, for the most part, in preventing recurrent venous ulceration, it was associated with morbidity and prolonged hospitalization . We have attempted to obtain the beneficial effects of perforator interruption by the less invasive procedure of subfascial endoscopic perforator vein surgery using laparoscopic instrumentation and limited or no hospitalization . A total of 31 consecutive operations were performed in 30 patients . Sixteen women and 14 men were entered into the study, and all of them had severe chronic venous insufficiency with either open or healed ulcers . Operations were carried out without gas insufflation, in 17 without a hemostatic tourniquet, and in 13 entirely on an outpatient basis . The 18 hospitalizations produced a total of 49 days of inpatient care (mean 2.72 days) . One to six perforating veins were encountered in these operations, and veins identified as perforators were electrocoagulated or clipped and sectioned . Sixteen limbs had severe chronic venous insufficiency or healed ulcers, and 15 had open ulcers . In 13 limbs, ulcers were intermittently present for 1 to 5 years . Seven of these healed within 4 weeks of operation and four others within 8 weeks . Two healed more than 8 weeks after surgery . In two limbs with ulcers that were present for 1 to 6 months, healing took place within 4 weeks of the operation in both . Complications included atelectasis in one patient, cellulitis requiring antibiotic therapy in three, wound hematomas not requiring intervention in two, and wound seroma not requiring therapy in one . This preliminary experience suggests that perforator vein interruption can be accomplished using existing instrumentation and a variety of technical modifications to achieve the objectives of the Linton operation without the attendant morbidity . Videoscopic instrumentation obtains benefits of subfascial perforator vein interruption without morbidity of the open operations . This preliminary study suggests that the operative procedure is attended by minimum morbidity without the need for rehospitalization . Long-term observation will be required to assess the procedure definitively, but the short-term objectives can be safely accomplished with minimum use of inpatient facilities. Br Poult Sci, 1996 May, 37(2), 435 - 42 Depletion of dietary sulphamonomethoxine and sulphadimethoxine from various tissues of laying hens; Furusawa N et al.; Sulphamonomethoxine (SMM) or sulphadimethoxine (SDM) was fed to laying hens at 400 mg/kg diet for 5 successive days . After withdrawal of the drugs, contents (mg/kg) of SMM and SDM in the blood, kidney, liver, ovary, muscle and adipose tissue were determined by HPLC . 2 . The disappearance of dietary SMM and SDM from the tissues of laying hens was rapid and, except for the liver, was very similar in all tissues . 3 . A common biological half-life (t1/2) of SMM in the above 6 tissues was estimated to be 5.2 h . The t1/2 of SDM in the liver was 6.9 h, significantly longer than that of 4.4 h in the other 5 tissues . The values were much shorter than 51/2 (reported elsewhere) for other drugs . 4 . Comparing the data found in this study with those obtained from previous papers, the depletion velocities of SMM and SDM from the hen's body were much faster than those from albumen in egg . The reason for this is probably related to the longer time period over which albumen formation occurs. Br Poult Sci, 1996 May, 37(2), 395 - 401 Effect of probiotic supplementation on growth, nitrogen utilisation and serum cholesterol in broilers; Mohan B et al.; 1 . The effect of dietary probiotic supplementation on the growth, nitrogen utilisation and serum cholesterol content of broiler chickens was studied in 2 trials . 2 . In experiment 1, the birds receiving the 0, 75, 100, 125 mg probiotic/kg diets had weight gains of 1204.0, 1272.0, 1268.3 and 1210.5, respectively at the end of 8 weeks of feeding . The group of birds fed on the 75 mg probiotic supplemented diet retained significantly (P < 0.01) more nitrogen than the control birds . Serum cholesterol content was lower in the probiotic-supplemented birds (93.3 mg/100 ml) compared to the control birds (132.2 mg/100 ml) . 3 . In the second experiment the probiotic plus antibiotic-supplemented group of birds had the maximum weight gain (1148.5 g) followed by antibiotic (1141.3 g), probiotic-supplemented (1128.4 g) and control birds (1045.6 g) after 6 weeks . Nitrogen retention was greatest in the antibiotic--(48.5%) followed by the probiotic--(46.5%), probiotic plus antibiotic-supplemented groups (46.3%) compared to 40.2% in control birds . 4 . The apparent metabolisable energy was greatest in birds receiving the probiotic plus antibiotic-supplemented diet (12.37 MJ/kg) followed by antibiotic--(12.00 MJ/kg), probiotic-supplemented birds (11.92 MJ/kg) than in control birds (11.62 MJ/kg) . Serum cholesterol was significantly (P < 0.01) lower in probiotic-supplemented birds (86.1 mg/dl) compared to 118.4 mg/dl in control birds. Farmaco, 1996 May, 51(5), 375 - 9 Synthesis and antitumour activity of fluorinated 1-aza and 1,8-diazaanthraquinones; Ramos MT et al.; A series of 3-fluoro-1-aza- and 1,8-diazaanthraquinones, structurally related to the antitumour antibiotic diazaquinomycin A, have been prepared by Diels-Alder reactions of 2-fluoro-2-propenal N, N-dimethylhydrazone and the corresponding quinones . These compounds showed potent in vitro activity against different tumour cell lines . They also showed some selectivity towards rapid-growth tumours when compared to other non-fluorinated analogues . In contrast with diazaquinomycin A, the azaanthraquinones studied here have not shown significant activity as thymidylate synthase inhibitors . Some compounds showed a high activity as inhibitors of protein, DNA and RNA biosynthesis. Actas Urol Esp, 1996 May, 20(5), 448 - 53 {Cancer of the penis: cooperative group of the province of Cadiz.(Andalusian Association of Urology)}; Acyclovir prophylaxis of oral herpes virus during bone marrow transplantation; Health Sciences Centre, Vancouver Hospital, British Columbia, CanadaOropharyngeal shedding of herpes viruses (herpes simplex, cytomegalovirus) was assessed in patients on standard acyclovir prophylaxis during bone marrow transplantation (BMT) to determine the frequency of viral shedding and to assess possible oropharyngeal complications that may be associated with viral reactivation in these patients . We conducted a prospective assessment of 83 patients receiving BMT . Patients were evaluated weekly and oral surveillance cultures were completed . Shedding of herpes simplex virus (HSV) was detected in the oropharynx of 2.9% of seropositive patients on prophylactic acyclovir, and only one case of clinical oral herpetic infection was seen . Cytomegalovirus (CMV) was cultured from the oropharynx in 13.3% of CMV seropositive patients provided with prophylactic acyclovir, but no oropharyngeal lesions were attributed to CMV reactivation . No correlation was seen between HSV and CMV pretransplant serology and severity of oral mucositis and acute graft versus host disease . No effect on time to engraftment was detected . This study supports the continuing use of acyclovir prophylaxis in HSV seropositive patients receiving BMT . Acyclovir prophylaxis was effective in preventing viral shedding in all but 2.9% of patients, and only one case of clinical infection was diagnosed . The frequency of CMV shedding was approximately four times that of HSV; however, no oral lesions were attributed to CMV. Int J Pediatr Otorhinolaryngol, 1996 May, 35(3), 213 - 22 Parapharyngeal abscess in children: the role of CT for diagnosis and treatment; Sichel JY et al.; Parapharyngeal abscess (PPA) in children is an uncommon deep neck space infection . Computerized tomography (CT) is an important diagnostic aid . However, CT scan is not specific in differentiating an abscess from cellulitis or inflammatory edema . A retrospective review of eight children with a CT diagnosis of PPA was undertaken . In three patients an abscess was surgically confirmed . In two patients surgical exploration did not reveal an abscess and in three the infection resolved with intravenous antibiotic therapy only . Although CT is a useful diagnostic tool for PPA, surgical intervention should be based mainly on the clinical status of the patient and the non-responsiveness to i.v . antibiotic therapy. Arch Mal Coeur Vaiss, 1996 May, 89(5), 641 - 4 {Coronary-cardiac fistula as a cause of tricuspid endocarditis treated by mitral homograft}; Lupoglazoff JM et al.; The authors report a rare case which is interesting from three points of view: tricuspid valve endocarditis in a child complicating a fistula between the right coronary artery and right ventricle with negative blood cultures but a positive serology for Coxiella burnetii . This mutilating tricuspid endocarditis was complicated by multiple pulmonary embolism of the right lung . After two months of antibiotic therapy the coronaro-cardiac fistula was closed and the tricuspid valve replaced with a mitral homograft . All cases of blood culture negative endocarditis require serological investigation to detect intracellular organisms which are difficult to diagnose and justify specific prolonged antibiotic therapy . Control serological tests are essential in the long-term because of the risk of chronic infection, especially in cases with prosthetic intracardiac material . Treatment, based mainly on tetracyclines, should be continued for at least two years. Pathol Biol (Paris), 1996 May, 44(5), 435 - 41 {Molecular typing by pulsed field gel electrophoresis of Stenotrophomonas maltophilia isolated in a department of hematology}; Fabe C et al.; Stenotrophomonas maltophilia is an important nosocomial pathogen . The increased isolates of S . maltophilia among hematology unit patients led to an epidemiological survey . Over 26 months, 24 strains isolated from 23 patients and an environmental isolate from blood pressure armband have been identified . The isolated were first analysed by the use of phenotypical markers: biotype, antibiotic susceptibility, but the minor differences observed justified a genotypic analysis . Pulsed field gel electrophoresis of genomic DNA was carried with XbaI and DraI restriction endonucleases by contour-clamped homogeneous electric field method (CHEF) . The data obtained showed a great genomic diversity within the species S . maltophilia . Nevertheless, the same restriction profile was found for 3 patients and 3 other profiles were obtained for 3 couples of patients hospitalized at the same time . All the other strains isolated from subjects hospitalized during the same period exhibited pulsotypes independent from each other . Compared to biotypes and antibiotic susceptibility, these results indicate field only with non modified primers, and the absence of 460 mutations was confirmed by sequencing . Two isolates P1 and P2, from a transplanted patient were amplified with both primers MCMM and MCMW: sequencing analysis shown the presence of a mixture of strains, one of them harbouring A- > G 1378 mutation . One resistant strain was amplified neither with MCMM nor with MCMW: a C- > T silent mutation at nt 1368 was present . As sequencing analysis confirmed PCR results, discriminative PCR enables isolates to be rapidly assessed for the presence or absence of 460 mutations . Moreover, it can distinguish Met to Val from Met to Ile mutations, and allows the analysis of mixtures of sensitive and resistant strains. J Immunoassay, 1996 May, 17(2), 133 - 44 Enzyme-linked immunosorbent assay of neocarzinostatin chromophore (NCS-chr) by use of a monoclonal antibody against NCS-chr analog; Mizugaki M et al.; A monoclonal antibody against NCS-chr was prepared and characterized . Because of the instability of NCS-chr, chemically synthesized stable analog compound, termed PS, was used as a hapten of immunogen . The obtained antibody, termed APS, reacted with NCS-chr, but neither with NCS, NCS-polystyrene-maleic acid conjugate (SMANCS), nor UV-irradiated NCS-chr . Epitope analysis using the compounds that have a structure similar to PS showed that APS recognized the total structure, particularly cyclopenten moiety, of PS . These results suggest that APS recognizes the enediyne structure of NCS-chr . Next, the inhibition enzyme-linked immunosorbent assay (ELISA) for determination of NCS-chr was established . The standard curve showed that the microgram order of NCS-chr were accurately measurable by the established ELISA . Furthermore, it was revealed that the established ELISA was more sensitive than the antibiotic activity determination, termed Bio-assay . The established ELISA will be useful as a quantitative method of NCS-chr. Int J Clin Pharmacol Ther, 1996 May, 34(5), 202 - 7 Multiple dose bioequivalence study with josamycin propionate, a drug with highly variable kinetics, in healthy volunteers; Van Hoogdalem EJ et al.; Josamycin is a macrolide antibiotic with considerable intra- and interindividual variability in kinetics . In the present study bioequivalence of an intact and dispersed josamycin Solutab tablet, containing 1,000 mg of josamycin in the form of josamycin propionate ester, was tested versus a Josacine 1,000 mg reference sachet . The design of this bioequivalence study was adapted to the drug's pharmacokinetic variability, comprising testing in steady-state, testing the reference in replicate, and maintaining a widened bioequivalence margin . The study was performed in a group of 24 male and 12 female healthy subjects, according to a 3-treatment 4-period crossover design . Blood sampling for establishing josamycin propionate and josamycin base serum level profiles were collected during the 12 h dosing interval on day 4 . Steady-state serum levels were reached on day 4 . With the reference sachet mean peak levels of 1.02 micrograms/ml and 0.36 microgram/ml were observed for parent drug and metabolite, respectively, reached at peak times of 1.5 h and 1.8 h . Comparable profiles were observed with the intact and dispersed Solutab tablets, both tending towards higher serum levels than the sachet . In terms of josamycin propionate levels as well as josamycin base levels, the intact and dispersed Solutab tablet was bioequivalent with the referent sachet within the preset 0.70-1.43 margins . Variability in josamycin kinetics proved to be substantial, maximum differences in peak levels and AUC values being about 10-fold between individuals, and 3-fold within individuals . Retrospectively, the multiple dosing regimen appeared not to result in a clear reduction of intrasubject variability. J Hosp Infect, 1996 May, 33(1), 55 - 61 A prospective audit of wound infection rates after caesarean section in five West Yorkshire hospitals; Nice C et al.; A three month prospective audit of wound infection following emergency and elective caesarean section was carried out in five West Yorkshire hospitals . Among 4076 women undergoing delivery in the five obstetric departments, the caesarean rate was 15.4% . The overall infection rate was 45/628 (7.2%) with a range of 2.5-17.2% between the five centres . The infection rate was 14/226 (6.2%) when antibiotics were used compared with 31/402 (7.7%) without antibiotics . The use of prophylactic antibiotics made no significant difference to the infection rate, which did not correlate with duration of labour or of ruptured membranes . The number of vaginal examinations correlated with the infection rate . In conclusion, the caesarean section rate observed was higher than that estimated for the UK as a whole, but was distorted by one centre with a high rate . For the other four hospitals the caesarean rate was unexceptional . The ratio of emergency to elective operations was comparable with recently reported values in the UK and the wound infection rate was within the widely varying limits found in previous studies . In view of the relatively low infection rate recorded without antibiotics, in the interests of cost effectiveness, prophylaxis may be limited in future to selected women at high risk . Because this was an audit rather than a randomized study we cannot exclude that this is already happening on an empirical basis. Unfallchirurg, 1996 May, 99(5), 346 - 50 {Bite wounds and their characteristic position in trauma surgery management}; Aigner N et al.; Bite wounds have a special position in traumatology because of their high complication rate compared to similar soft tissue wounds caused by other reasons . The authors report in a retrospective study about the results of 525 patients with bite wounds . In 98 (18.7%) cases the wounds were sutured primarily after surgical revision when there was no sign of infection . Antibiotic therapy (a combination of amoxicillin and clavulan acid) was given to 109 patients (20.8%) who had infected wounds or who were at greater risk for infection (e.g., extremely large wounds, large hematoma) . Antibiograms were only made when the wounds had already been infected . The total infection rate came to 11.8%, with 5.2% infected facial bites, 11.3% lower extremity, 18.6% upper extremity and 18.8% hand bite wounds . The infection rate after primary suture was 10.2% (3.2% at the face, 18.8% at the upper extremity and 25% each in the hand and the lower extremity) . The average time period from the trauma to the first medical treatment amounted to 11 h in the infected wounds and 2 h in the non-infected ones . Cat bites became infected in 37.5%, dog bites in 14.9%. J Antimicrob Chemother, 1996 May, 37(5), 1017 - 21 Concentration of teicoplanin in the serum of adults with end stage chronic renal failure undergoing treatment for infection; Mercatello A et al.; We examined the adequacy of the following schedule for the administration of i.v . teicoplanin to patients with chronic renal failure: three doses of 6 mg/kg at 12 h intervals, a fourth dose 24 h later and then subsequent doses every 72 h . Eight infected patients undergoing dialysis were investigated, with serum antibiotic concentrations measured ten minutes before and one hour after administration . Mean trough concentrations were 6.9 +/- 3.1 mg/L on day two, 9.8 +/- 4.4 mg/L (day three), 9.2 +/- 4.8 mg/L (day six), 10.9 +/- 5.5 mg/L (day nine), 12.1 +/- 6.1 mg/L (day 12) and 14.8 +/- 8.0 mg/L (day 15) . The proposed schedule achieved adequate trough serum teicoplanin concentrations by 48 h in six out of eight patients examined . The dosage regimen was well tolerated. J Antimicrob Chemother, 1996 May, 37(5), 975 - 86 A meta-analysis of clinical studies of imipenem-cilastatin for empirically treating febrile neutropenic patients; Deaney NB et al.; There are many clinical studies comparing antibiotic treatments, but the majority are too small to have sufficient power to be reasonably certain of detecting statistically a moderate treatment effect . For example, few of the 19 studies published on imipenem-cilastatin for empirically treating febrile neutropenic patients were able to show any significant treatment effect in either direction when compared with alternative regimens . We therefore undertook a meta-analysis of these studies and made 21 pairwise comparisons of a control regimen with imipenem-cilastatin . Eleven comparisons were made between imipenem-cilastatin and a beta-lactam-aminoglycoside combination, and a further 10 between the carbapenem and a beta-lactam regimen either alone or combined with a glycopeptide or other beta-lactam antibiotic . These two data sets were analysed separately . Imipenem-cilastatin demonstrated a beneficial treatment effect over that achieved by aminoglycoside containing control regimens, yielding a typical odds ratio (OR) of 0.77 (95% CI 0.61 to 0.98) . A beneficial treatment effect for the carbapenem regimen was also shown against regimens that did not include an aminoglycoside, with the typical OR being 0.67 (95% CI 0.54 to 0.84) . Although there was clinical heterogeneity between studies, the treatment effect itself was relatively homogenous . These results show meta-analysis to be a useful aid for interpreting the data from clinical studies that are intrinsically too small to provide conclusive results. J Antimicrob Chemother, 1996 May, 37 Suppl A, 57 - 63 A review of the penetration of sparfloxacin into the lower respiratory tract and sinuses; Wise R et al.; There are a number of potential sites of infection in the lower respiratory tract . This review summaries the nature of these sites and the ways in which antibiotic penetration can be studied . The results of a single-dose and a multiple-dose study of the penetration of sparfloxacin into the respiratory tract are also provided . After a single oral dose of sparfloxacin 400 mg or a 400 mg loading dose on day 1 followed by 200 mg daily for 2 days, sparfloxacin concentrations in the bronchial mucosa, epithelial lining fluid and alveolar macrophages were higher than the corresponding concentrations in serum . Compared with other fluoroquinolones, sparfloxacin achieves higher concentrations at these sites . Sparfloxacin diffusion into maxillary sinus mucosa has been studied in patients with chronic maxillary sinusitis undergoing surgery . High concentrations of sparfloxacin were detected in sinus mucosa 2 to 5 h after administration of a single dose of sparfloxacin 200 or 400 mg. Pediatr Hematol Oncol, 1996 May-Jun, 13(3), 217 - 29 Infection risk factors in febrile, neutropenic children and adolescents; Jones GR et al.; We studied 276 fever episodes with an absolute neutrophil count (ANC) < 500/mm3 to determine patient characteristics predicting serious infection . Infections occurred in 38% of patients . Blood cultures were positive in 58% of documented infections . There was no difference in the rates of infection or positive blood culture when ANC was < 200/mm3 compared with a higher ANC . However, certain high risk infections were more common with an ANC < 200/ mm3 . Leukemia patients had more infections compared with other groups . Serious infections were more common during induction therapy or relapse . Infection incidence varied significantly with patient age and onset of fever in the inpatients . Less than one fifth of febrile neutropenic episodes had no risk features for serious infection . We conclude that several clinical characteristics correlate with serious infection in febrile, neutropenic children and adolescents receiving modern supportive care . Despite improvements in supportive care measures, most febrile, neutropenic patients need close observation and empiric intravenous antibiotic therapy. Protein Sci, 1996 May, 5(5), 857 - 61 The structural homology between uteroglobin and the pore-forming domain of colicin A suggests a possible mechanism of action for uteroglobin; de la Cruz X et al.; Although the exact physiological function of uteroglobin is not known, it has been suggested that it may function by inhibiting phospholipase A2 . We have found that the uteroglobin fold is embedded in that of the poreforming domain of colicin A . Colicin A is an antibiotic protein that kills sensitive Escherichia coli cells by forming a pore in their phospholipid membrane . The RMS deviation between the C alpha atoms after the structural alignment is 2.39 A for the 52 superimposed residues . In the alignment, uteroglobin helices 1, 2, 3, and 4 align with colicin A helices 6, 7, 3, and 4, respectively . The motif is strongly amphipathic in both proteins . On the basis of this common structural motif and of known experimental data on both proteins, we propose that UG binds to the membrane surface by lying on it monotopically . The phospholipase A2 inhibition would follow this initial binding step. Orthopedics, 1996 May, 19(5), 389 - 94 Bone graft in hindfoot arthrodesis: allograft vs autograft; McGarvey WC et al.; From 1990 to 1992, all arthrodeses of the so-called triple joints, combined or isolated and performed by one surgeon, were reviewed to allow a minimum follow up of 18 months from the time of the index procedure . Type of bone graft was selected based on the patients' decision after the risks of each were explained by the surgeon . There were 37 patients undergoing 41 procedures (4 bilateral) including double and triple arthrodesis, as well as isolated subtalar fusions . Twenty-nine of these were performed for either degenerative or posttraumatic arthritis . Ten others were performed for joint incongruity resulting from posterior tibial tendon insufficiency, and the rest for hemiparesis or residual clubfoot . All patients were placed into a routine postoperative regimen of casting, bracing, weight bearing, and therapy . They were evaluated based on subjective complaints, physical examination, and postoperative radiographs . Any patient suspected of having a nonunion underwent a computed tomography scan for confirmation . Overall, 24 patients received allografts and 17 iliac crest grafts . There were four nonunions, three of which utilized banked bone graft, with the only nonunion in the autograft group occurring in a patient following open calcaneus fracture . Of the four nonunions, three opted for revision surgery and the only one to choose allograft again incurred the only recurrent nonunion . There were two infections, one in each group, resulting in prolonged intravenous antibiotic therapy. Cancer Gene Ther, 1996 May-Jun, 3(3), 143 - 50 Transduction of human renal carcinoma cells with human gamma-interferon gene via retroviral vector; Nayak SK et al.; We used a retroviral vector containing a human gamma-interferon (gamma-IFN) gene to transduce 13 renal carcinoma cell lines . The transduction efficiencies ranged from 0% to 60%, as determined by using an analogous vector containing the LacZ marker gene . In addition, gene-transferred resistance to the antibiotic neomycin was used to select for transduced cells . Nine of 13 lines were successfully transduced . Transduction was associated with the morphologic change of elongation, and there was a marked decrease in cell growth rate . Transduced cells secreted varying amounts (20-1076 pg/10(6) cells/d) of gamma-IFN as measured by enzyme-linked immunosorbent assay for at least 2 to 3 weeks after transduction (including 1 day of transduction, 6-7 days of selection, and an additional 8-12 days before the first passage of the transduced cells) . Human leukocyte antigen (HLA) class II expression was markedly increased in six of seven cell lines; HLA class I expression was significantly increased in two of eight lines . Transduced cells that were subjected to cryopreservation after irradiation still produced gamma-IFN and expressed HLA class I and II antigens, although generally at lower levels than before these manipulations . This study confirms that retroviral vector transduction of the human gamma-IFN gene into renal carcinoma cells is feasible and associated with persistent production of gamma-IFN and increased expression of HLA class I and II molecules, and these effects are retained after irradiation and cryopreservation . This suggests that an autologous tumor cell vaccine trial with irradiated gamma-IFN gene-transduced renal carcinoma cell is rationale and feasible. J Reprod Med, 1996 May, 41(5), 375 - 8 Pyomyoma after uterine instrumentation . A case report; Tobias DH et al.; BACKGROUND: Since 1945, only 10 cases of pyomyoma have been described in the literature . Four were related to pregnancy but none to elective abortion or uterine instrumentation . CASE: A 32-year-old woman was admitted to the hospital with a history of lower abdominal pain, nausea, vomiting and low grade fever with a past medical history significant for uterine leiomyomata and a second-trimester elective abortion 10 weeks prior to admission . Pelvic sonography demonstrated an enlarged uterus with a mass consisting of cystic and solid components . Uterine curettage revealed blood clots and scanty endometrial tissue . After no improvement following antibiotic therapy and nondiagnostic uterine curettage, an exploratory laparotomy was performed . It revealed peritonitis with multiple pyomyomas draining purulent material . CONCLUSION: Although rarely reported, pyomyoma should be considered in the setting of a recent history of uterine instrumentation, signs of infection and a uterine myoma. Pathologe, 1996 May, 17(3), 231 - 4 {"Walking pneumonia" in primary sarcoma of the pulmonary artery}; Theile A; A 74-year-old man suffered from symptoms of a left upper lobe pneumonia . Additional retrosternal masses were proved . Progression in the left upper lobe occurred in spite of antibiotic therapy; infiltrations of the right lower lobe were seen . No germs could be identified . Bronchoscopy and mediastinoscopy showed no pathological findings . His general health became worse, and the patient died under the clinical diagnosis of "wandering pneumonia" with finally suspicion of fulminant pulmonary artery embolism . Autopsy findings revealed an advanced stage of pulmonary artery sarcoma with myocardial infiltration and metastases in both kidneys and thyroid gland . General manifestation of pulmonary artery sarcoma usually are symptoms similar to those caused by pulmonary artery embolism with obstruction of pulmonary arterial flow . The unusual constellation of clinical findings similar to colliquating pneumonia results in secondary infection due to tumorous pulmonary infarction . The difficulties in diagnosis by biopsy are caused by primary intravascular growth of the neoplasms . Therefore early diagnosis in an operable tumor stage by means of CT, MR, and angiography is very important. Kansenshogaku Zasshi, 1996 May, 70(5), 506 - 11 {Prevention of infections in a case with myelodysplastic syndrome by an intermittent subcutaneous administration of G-CSF}; Saburi Y et al.; An 83-year-old male was admitted to our hospital because of pancytopenia and low grade fever on April 19, 1993 . On admission, hematological data were as follows: WBC 1,000/microliters with 19% neutrophils, RBC 367 x 10(4)/microliters, Hb 9.5 g/dl and platelets 6.7 x 10(4)/microliters . Bone marrow examination revealed 6.6% myeloblasts and 33.5% erythroblasts . Morphological abnormalities included hypersegmentation, degranulation and pseudo-Pelger's nuclear anomaly in neutrophils . Based on these findings the diagnosis of refractory anemia with excess of blasts (RAEB) of the myelodysplastic syndrome (MDS) was made and therapy with low dose Cytarabine (Ara-C) was initiated in April 1993 . The patient had two episodes of severe pneumonia in June and July . Therefore, 75 micrograms/day of G-CSF was given in addition to antibiotic therapy for the second episode of infection in July . Thereafter the severe infection subsided, and G-CSF administration was switched to an intermittent schedule (75 micrograms twice a week) since September . Cytarabine ocfosfate (100 mg/day) was added for 10-14 days at interval 1-2 months from October,1993 . He has been well with no episode of infection for more than two year . One major concern regarding the clinical application of G-CSF in MDS patients is related to the possible stimulation of leukemic cell proliferation . Frequent hematological monitoring is necessary in patients with RAEB who are prone to develop acute myeloid leukemia . However, we administered G-CSF at a relatively low dose twice a week for over two year and could successfully prevent infections without inducing the leukemic changes. Br J Ophthalmol, 1996 May, 80(5), 413 - 5 Clinical evaluation of carbocyclic oxetanocin G eyedrops in the treatment of herpes simplex corneal ulcers; Shiota H et al.; BACKGROUND: Acyclovir (ACV) ophthalmic ointment is effective in the treatment of herpetic keratitis . However, when applied, the ointment has an unpleasant feeling and some cases are resistant to ACV . A new antiviral compound, carbocyclic oxetanocin G (C.OXT-G) has potent anti-herpes simplex virus activity and high water solubility, so the clinical effect of C.OXT-G eyedrops on ulcerative herpetic keratitis was evaluated . METHODS: Studies were conducted on the corneal ulcers in 37 eyes of 27 patients . Patients with typical dendritic or geographic corneal ulcers were treated with 0.1% C.OXT-G eyedrops, applied five times a day, together with eyedrops of an antibiotic applied four times a day . The eyes were examined at least twice a week until the ulcers healed, and thereafter at intervals for up to 3 months . RESULTS: All of the ulcers healed, their average healing time being 4.9 (SD 2.2) (range 2 to 9) days . The ulcers in 20 of the 37 eyes were induced by the use of corticosteroid or immunosuppressive drugs, and their average healing time was 4.8 (2.3) days . No adverse drug reactions were seen during the observation period in this trial . CONCLUSION: Eyedrops containing 0.1% C.OXT-G are excellent and safe for treatment of herpes simplex corneal ulcers in humans. Nephrol Dial Transplant, 1996 May, 11(5), 830 - 2 Survey of permanent central venous catheters for haemodialysis in the UK; Kumwenda MJ et al.; BACKGROUND . Venous catheter haemodialysis may be necessary in some patients without arterio venous fistulae on dialysis for end-stage renal failure . We conducted a survey to compare management of these catheters in different units in the UK . METHODS . Postal questionnaires were sent to nurses in charge of 81 renal units in the UK for a twelve month study period in 1994 to find out the type of catheter used, catheter after insertion care, the rate and management of exit site infections, and bacteraemia . RESULTS . (1) Total number of questionnaires returned 66 (81.5%) . (2) 63.6% of renal units used double lumen Permcath catheters, 16.7% single lumen (Francis/Kimal, Gambro or Vascath), 10.6% use both double and single lumen catheters and 9.1% of renal units only use temporary polyurethane catheters . (3) Catheter exit site aseptic dressing technique was used in 84.8% of renal units, clean technique in 15.2% . 66.8% change dressings at each dialysis session, 22.7% weekly . The majority of renal units (63.6%) had one nurse to change the dressing, used Betadine as a cleaning agent and Mepore to cover the exit site . (4) 75.8% did not know the exact incidence of episodes of sepsis and/or exit site infections . Flucloxacillin was the antibiotic of choice for each catheter related sepsis episode . CONCLUSION . During this study period most renal units used Permcaths as first choice for long term catheter dialysis, the after insertion care of which varied . The number of episodes of sepsis was unknown . We suggest UK collection of data for all long term catheters and related problems for audit purposes. Curr Genet, 1996 May, 29(6), 587 - 90 Transformation of the plant pathogenic fungus, Rhynchosporium secalis; Rohe M et al.; The barley leaf scald fungus, Rhynchosporium secalis, was transformed to hygromycin-B and phleomycin resistance using the hph gene from E . coli and the ble gene from Streptoalloteichus hindustanus under the control of Aspergillus nidulans promoter and terminator sequences . Plasmid DNA was introduced into fungal protoplasts by PEG/CaCl2 treatment . Transformation frequencies varied from 59 to 493 transformants per 10 microg of DNA and 5 x 10(7) protoplasts . The antibiotic-resistant phenotype appeared to be stable under selective, as well as under non-selective, conditions for several generations . Co-transformation using the E . coli uidA gene under the control of A . nidulans promoter and terminator sequences on a non-selectable plasmid occurred at frequencies of up to 66%. World J Surg, 1996 May, 20(4), 471 - 3 Multiple organ failure: is it disappearing? Levine JH, Durham RM, Moran J, Baue A. The incidence of multiple organ failure (MOF) during the last decade has been reported variously as 2% to 25%, depending on the patient population examined . The mortality rate from this devastating complication ranges from 40% to 80% . Although the incidence has not changed during the last decade, it does not mean that there has been no progress . Tertiary centers are now seeing trauma and nontrauma patients who have more significant underlying disease and injuries . Likewise, a higher percentage of our trauma patients are now referred from outside institutions where there may not be the facilities to administer the complex, rapid resuscitation these patients require . Prevention of MOF remains its best treatment . Rapid, adequate volume resuscitation, adequate nutrition, appropriate antibiotic usage, and aggressive pulmonary management are important for preventing the downward physiologic spiral that leads to MOF and death . Once MOF has occurred, it is not clear that these same measures are as effective in altering outcome. Anal Biochem, 1996 May 1, 236(2), 215 - 20 Inhibition assay for the binding of biotinylated von Willebrand factor to platelet-bound microtiter wells in the presence of ristocetin or botrocetin; Miura S et al.; We developed a solid-phase inhibition assay for the binding of biotinylated von Willebrand factor (vWF) to platelet glycoprotein (GP)Ib based on an enzyme-linked immunosorbent assay (ELISA) with platelet-bound microtiter wells . Washed platelets were immobilized onto the microplates via the anti-GPIIb/IIIa monoclonal antibody (mAb) VNR-5 . In the presence of an antibiotic ristocetin (1 mg/ml, final) or the snake venom botrocetin (2 micrograms/ml, final), biotinylated vWF bound to the affixed platelets with half-maximal binding occurring at a vWF concentration of approximately 2 micrograms/ml . Several specific inhibitors of the binding of vWF to GPIb abolished the interaction of biotinylated vWF with GPIb in a dose-dependent fashion, with comparable protein concentrations to those seen in the liquid-phase inhibition assay using 125I-vWF . These inhibitors included mAb against vWF (NMC-4), mAb against GPIb (AP-1), and two vWF fragments containing vWF's putative GPIb-binding domain, namely a 39/34-kDa dispase-digested vWF fragment and a recombinant vWF fragment . Thus, this new assay is a convenient alternative to the conventional inhibition assay using 125I-vWF. CA Cancer J Clin, 1996 May-Jun, 46(3), 165 - 84 Hematopoietic growth factors; Bociek RG et al.; Over the past ten years, the availability of pharmacologic quantities of hematopoietic growth factors has opened many avenues of study in basic science and clinical investigation . Numerous studies performed to date have demonstrated significant benefits from the use of these cytokines . The side effect profiles, particularly for "later acting" growth factors, indicate that they are generally well tolerated by most patients . The table summarizes the potential indications for hematopoietic growth factor use as discussed in this article, as justified by current evidence of benefit, harm, and cost effectiveness resulting from their use in various clinical settings . It has been clearly demonstrated in standard-dose chemotherapy regimens that these agents shorten the duration of myelosuppression, reduce the incidence of significant infection, can shorten hospital stay, and reduce antibiotic use for most patients, although the cost/benefit ratio for growth factors such as G-CSF makes this a cost-effective approach only for regimens with a high (40 percent or more) incidence of febrile neutropenia . Limited indirect evidence supports the use of growth factors in patients with a prior episode of fever and neutropenia . The suppressive approach to growth factor use could potentially benefit patients with documented infection or clinical deterioration, but it has not otherwise been shown to be a particularly effective or cost-effective approach . Administration of hematopoietic growth factors has been instrumental in facilitating both autologous and allogeneic peripheral progenitor cell mobilization and techniques such as ex vivo expansion . There is an increasing body of data supporting the use of high-dose chemotherapy regimens with progenitor cell rescue for a number of malignancies and limited data supporting the benefits of maintaining dose-intensity for certain malignancies in standard-dose settings . Although of continuing concern, clinically significant evidence of disease stimulation and recurrence has not been unequivocally demonstrated in studies to date . A comprehensive set of evidence-based guidelines has recently been published by the American Society of Clinical Oncology . As often is the case, current studies have perhaps generated more questions than answers . Future investigation will undoubtedly focus on use of hematopoietic growth factors in conjunction with other techniques, such as outpatient-based treatment of febrile neutropenia, CD34-positive stem cell selection in autologous transplantation, selective manipulation of T-cell subsets (to decrease the incidence of severe graft-versus-host disease) in allogeneic transplantation, and high-dose therapy with stem cell transplantation. J Infect Dis, 1996 May, 173(5), 1260 - 2 The public health impact of Lyme disease in Maryland; Coyle BS et al.; The purpose of this study was to estimate the health burden imposed by Lyme disease (LD) in Maryland during 1992 and 1993 . A cross-sectional 1-in-15 survey of physicians (total, 1200) in Maryland was conducted to estimate the incidence of diagnosed LD, presumptive cases of LD, patients with tick bites, and diagnostic tests ordered for LD . Results show that LD is underreported by 10- to 12-fold in Maryland, that 80% of cases are managed by primary care physicians, and that there is discordance between the actual clinical treatment of patients and the recommended approach . In addition, the much greater numbers of patients treated for presumptive LD, seen and given prophylaxis for tick bites, and having diagnostic tests indicate that real and perceived LD is a far greater public health problem and uses more medical resources than official surveillance data suggest. Endocrinology, 1996 May, 137(5), 1894 - 903 Type I procollagen production and cell proliferation is mediated by transforming growth factor-beta in a model of hepatic fibrosis; Eghbali-Fatourechi G et al.; Fibrosis is a significant component of advanced chronic inflammatory liver diseases and is caused by the accumulation of extracellular matrix, including type I procollagen . The mechanism by which fibrosis develops in liver tissue remains unknown . We tested the effects of transforming growth factor beta 1 (TGF-beta), a cytokine that alters cell differentiation and proliferation, and bleomycin, a cytotoxic glycopeptide antibiotic, on cultured isolated rat hepatocytes . TGF-beta (1 ng/ml) inhibited radiolabeled thymidine incorporation 39% at 24 h and 69% at 48 h . Inhibition of hepatocyte proliferation was dose dependent . Bleomycin (1 microgram/ml) significantly inhibited radiolabeled thymidine incorporation at 48 h (44%) . Neutralizing antibody to thymidine incorporation at 48 h (44%) . Neutralizing antibody to TGF-beta (TGF-beta-Ab) attenuated the inhibition of proliferation by TGF-beta and bleomycin in a concentration-dependent manner . The addition of either TGF-beta or bleomycin increased immunostaining of type I procollagen in hepatocytes . The addition of TGF-beta-Ab alone increased cell proliferation, suggesting that neutralization of endogenous TGF-beta may attenuate the inhibition of hepatocyte proliferation . These data suggest that the hepatocyte contains type I procollagen and, under some conditions, produces TGF-beta . We propose that procollagen production in rat hepatocytes is induced by TGF-beta and may be related to endogenous production of this cytokine in response to cell injury . The cytotoxic effect of bleomycin is mediated by TGF-beta and inhibition of TGF-beta and bleomycin with TGF-beta-Ab attenuates the additive effects of those compounds on isolated rat hepatocytes . These data provide a model of collagen expression in isolated rat hepatocytes. J Gen Virol, 1996 May, 77 ( Pt 5), 913 - 7 Sensitivity to the parvovirus minute virus of mice as a probe for azatyrosine-mediated phenotypic reversion of spontaneously transformed cells; Koering CE et al.; It has been shown that cells transformed by known oncogenes could be reverted to an untransformed phenotype by the antibiotic Azatyrosine (AzTyr) . In order to evaluate the reverting effect of AzTyr on five spontaneously transformed FR3T3C cell clones, we performed three assays: soft agar clonability, tumorigenicity in nude mice and susceptibility to killing by the parvovirus minute virus of mice (MVMp) . In contrast to untransformed cells, transformed or tumorigenic cells are permissive for the lytic replication of MVMp and are killed . Our results demonstrate that although the cell populations that emerged after AzTyr treatment of FR3T3C clones had different phenotypes (two were untransformed and two had an altered transformed phenotype), they all behaved like untransformed cells, as judged from their resistance to MVMp infection . Our results demonstrate that susceptibility to MVMp is a valuable way to monitor the reversion. Arch Intern Med, 1996 Apr 22, 156(8), 889 - 94 Effect of isoniazid chemoprophylaxis on HIV-related mycobacterial disease; Graham NM et al.; OBJECTIVES: The aims of this study were to (1) identify trends and risk factors for mycobacterial disease and (2) determine the effect of expanded access to isoniazid chemoprophylaxis on tuberculosis incidence . METHODS: A prospective observational cohort study was conducted among community-based injecting drug users (IDUs); 2960 IDUs (942 human immunodeficiency virus {HIV} seropositive) were followed up from January 1988 to June 1994 . Directly observed chemoprophylaxis with twice-weekly isoniazid (10 to 15 mg/kg) was offered to purified protein derivative (PPD) tuberculin-positive (> or = 5-mm induration diameter in HIV-seropositive subjects and > or = 10-mm diameter in HIV-seronegative subjects) individuals but not to those with cutaneous anergy . Overall and annual incidence rates of disease due Mycobacterium tuberculosis, Mycobacterium avium complex, and other atypical mycobacteria were estimated using Poisson regression . RESULTS: HIV seropositivity was the strongest risk factor for tuberculosis, M avium complex, and other mycobacterial disease (relative risk {RR}, 3.8, 17.2, and 6.9, respectively) . Median CD4 lymphocyte cell counts for the three groups of mycobacterial disease were 0.17, 0.03, and 0.02 x 10(9)/L (167/microL, 30/microL, 18/microL) within 6 months of diagnosis (before or after) . Overall incidence rates of tuberculosis, M avium complex disease, and other mycobacterial disease were 1.9, 8.8, and 2.7 per 1000 person-years, respectively . Tuberculosis incidence peaked in 1991 at six per 1000 person-years . However, after access to directly observed preventive therapy was expanded for tuberculin-positive subjects, incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994 . During this period the number of PPD-positive patients who completed at least 26 weeks of therapy (or were still receiving isoniazid) more than tripled (from 21 to 70) . None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy . In addition, no tuberculosis developed among participants with cutaneous anergy . Calendar trends in risk for M avium complex and tuberculosis diverged after expanded access to isoniazid prophylaxis . Compared with 1988-1989, risk of M avium complex increased sevenfold . Tuberculosis risk fell 83% from the peak risk in 1990-1991 . CONCLUSIONS: Expanded access to directly observed isonazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83% drop in tuberculosis incidence, while in the same period M avium complex incidence significantly increased . These population-based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous energy. Fortschr Med, 1996 Apr 20, 114(11), 136 - 40 {Treatment of persistent diarrhea with S . boulardii in returning travelers . Results of a prospective study}; Kirchhelle A et al.; AIM: The efficacy and tolerability of Saccharomyces boulardii (S.b.) were investigated in patients with diarrhea contracted while travelling abroad . METHOD: The efficacy of S.b . was determined on the basis of the frequency and consistency of stools (fewer than 3 unformed stools a day), and symptom changes . A total of 95 patients (49 females, 46 males) aged between 19 and 69 (mean age 32) years were treated with S.b . at a daily dose of between 150 and 450 mg (mean 428 mg) (3 x 1-3 capsules) . RESULTS: Prior to admission to the study, diarrhea had persisted for an average of 11 days; under treatment with S.b . it cleared up after a mean of 5 days . A tendency towards greater efficacy in patients returning from The Middle East and South America was noted . Tolerability was assessed to be very good or good by almost all participants, with side effects occurring in only 2 cases . CONCLUSION: The study demonstrates that S.b . is both effective and well tolerated when used for the treatment of persistent diarrhea (mean duration 11 days) that had often failed (67% of the cases) to respond to previous antidiarrheal or antibiotic drugs. J Chromatogr A, 1996 Apr 19, 731(1-2), 123 - 37 Facile liquid chromatographic enantioresolution of native amino acids and peptides using a teicoplanin chiral stationary phase; Berthod A et al.; The glycopeptide antibiotic teicoplanin is shown to be a highly effective stationary phase chiral selector for the resolution of underivatized amino-acid and imino-acid enantiomers . Fifty four of these compounds (including all chiral protein amino acids) as well as a number of dipeptides were resolved . Hydro-organic mobile phases are used and no buffers or added salts are needed in most cases . Hence the purified analytes are easily isolated in pure form, if needed, by evaporating of the solvent . The effect of pH, organic modifier type and amount are discussed . The enantioselective separation mechanism is examined using both molecular modeling and retention data . The strongest stereoselective interaction is for carboxy-terminated D-amino-acids . In case of peptides, it is not necessary for these to be a D-, D-, terminal sequence for strong interactions . In some cases, including Ala-Ala, the L-, D-, terminal sequence showed greater interaction with the teicoplanin chiral stationary phase. Blood, 1996 Apr 15, 87(8), 3143 - 50 A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia . Berlin-Frankfurt-Münster Study Group; Welte K et al.; Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia (ALL) are good, with event-free survival (EFS) rates over 70% . However, for a subset of patients characterized by high-risk (HR) features the outcome is less favorable, with EFS rates below 50% . Intensification of chemotherapy may improve the outcome for those patients, but increased toxicity, particularly myelosuppression, limits the escalation of dose intensity . Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosuppression after cancer chemotherapy in adults . The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy . Patients with HR pediatric ALL were randomized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Munster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously . In both groups, the planned interval between chemotherapy courses was a minimum of 21 days . We report here interim results of 34 patients . The incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in the control group (P = .007) . In addition, the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient (P = .02) . Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group (8% v 15%; P = .04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient (P = .02) . A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF (P = .007) . With a median follow-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12% . In conclusion, r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule. Biochemistry, 1996 Apr 9, 35(14), 4265 - 70 In vitro selection analysis of neomycin binding RNAs with a mutagenized pool of variants of the 16S rRNA decoding region; Famulok M et al.; An in vitro selection for neomycin B binding was carried out with an RNA pool containing a 47-nucleotide domain of the decoding region of 16S ribosomal RNA, mutated at 30% per base position . The degenerate region was comprised of an oligonucleotide analogue ("motif A") of the decoding region in 30S subunits which has previously been shown to interact with the aminoglycoside antibiotic neomycin B and tRNA ligands . After five cycles of selection/amplification, RNA sequences were isolated which specifically bound to neomycin B . Cloning and sequencing showed that none of the isolated clones shared primary sequence or secondary structure homology with the decoding region of 16S RNA . Instead, a new set of sequences was isolated which could be folded into a defined hairpin structure designated as motif B . We investigated the affinity of motif A, motif B, the unselected pool RNA, and the corresponding unmutagenized "parent" RNA to neomycin B at different Mg2+ concentrations . Under buffer conditions of low ionic strength all RNAs tested bound nonspecifically to neomycin B . However, motif B bound to neomycin B at Mg2+ concentrations at which binding of the other RNAs tested was significantly lower or not detectable . This is consistent with motif B exhibiting a higher affinity for neomycin B than motif A under these conditions . Motif B has previously been isolated from an in vitro selection to identify RNA sequences with affinity to neomycin B using a completely randomized RNA pool which shared no relationship to motif A . Our results indicate that motif B might represent a highly optimized RNA sequence for neomycin B binding; conversely, the A-site motif in 16S rRNA (motif A) might not be an optimal target for neomycin B recognition. Br J Hosp Med, 1996 Apr 3-16, 55(7), 388 - 93 Modern diagnosis and management of genital Chlamydia trachomatis infection; Robinson AJ et al.; Chlamydia trachomatis infection is now the commonest bacterial, sexually transmitted infection in the UK . Uncomplicated genital chlamydial infection often does not produce symptoms in men or women, but patients may present with sequelae . New diagnostic techniques are available to identify C . trachomatis more easily and new antibiotic regimens provide effective treatment . These factors, together with heightened awareness within the medical profession and the general population, should help to reduce the prevalence of this infection. Biochim Biophys Acta, 1996 Apr 3, 1280(1), 98 - 106 {3H}Bafilomycin as a probe for the transmembrane proton channel of the osteoclast vacuolar H(+)-ATPase; Mattsson JP et al.; Bone resorption by the osteoclast is dependent on acidification of the bone surface by a vacuolar type H+-ATPase (V-ATPase) present in the ruffled membrane of the actively resorbing cell . V-ATPases are a highly conserved family of proton pumps consisting of two functional complexes: a cytoplasmic catalytic sector (VC) and a membrane bound proton channel (VB) . Bafilomycin A1, a macrolide antibiotic, is a highly potent inhibitor of V-ATPases, and inhibits bone resorption in vitro in isolated rat calvariae . In order to investigate the binding of bafilomycin to the osteoclast V-ATPase, we used a tritiated bafilomycin which had been prepared by acetylating the 21-hydroxyl group of bafilomycin A1 . Osteoclast ruffled membrane vesicles were prepared from purified chicken osteoclasts by differential centrifugation and proton transport in these vesicles was shown to be inhibited by {3H}bafilomycin (IC50 approximately 2 nM) . Control membrane vesicles or membrane vesicles partially inhibited with {3H}bafilomycin were solubilized and separated by centrifugation on 15-30% glycerol gradients . V-ATPase activity and reconstitutable proton transport activity could be recovered in high density fractions of the gradient . However, the peak of {3H}bafilomycin radioactivity (>70% of total radioactivity in the gradient) was present in a single peak at lower density . Antibodies against subunits of VC (70, 56 and 40 kDa) reacted only in fractions containing the peak V-ATPase activity whereas an antibody to the 39 kDa subunit of VB reacted both with fractions containing the peak V-ATPase activity but also, and more strongly, in fractions containing the peak {3H}bafilomycin . The fractions in the control gradient corresponding to the peak of {3H}bafilomycin were reconstituted into liposomes and shown to mediate passive bafilomycin A1-inhibitable proton conductance . SDS-PAGE followed by autoradiography, indicated that the bafilomycin was not covalently bound to the V-ATPase or the proton channel . Quantification of VB by {3H}bafilomycin binding or by antibody staining suggested an excess of the free proton channel to that of the intact holoenzyme . A corresponding amount of free catalytic sector could not be found in any fraction throughout the isolation procedure of the V-ATPase from the initial homogenate . Thus, in conclusion, bafilomycin inhibits the V-ATPase by binding tightly but non-covalently to the proton channel region of the V-ATPase which appears to be present in excess over the intact holoenzyme in the osteoclast . The possible role of an excess of the proton channel subcomplex in the osteoclast is discussed. Antibiot Khimioter, 1996 Apr, 41(4), 7 - 15 {Stabilization of roseofungin by antioxidants}; Shenin IuD et al.; Stabilization of roseofungin, a pentaene antibiotic, by antioxidants of different chemical structure was studied . The highest inhibitory effect was observed with the use of antioxidants X-1 (a partially hydrated oxyquinoline) and P-1 (a polyaromatic nitrogen containing compound) . The results of the study correlated with the data on nystatin and levorin . The stabilizing effect markedly depended on the temperature: with increasing of the temperature the antioxidant effect decreased . The spectrophotometric study revealed that the decrease of the biological activity of the antibiotic in the presence of the antioxidants was more pronounced than the change of its structure. Antibiot Khimioter, 1996 Apr, 41(4), 44 - 50 {Effect of lomefloxacin on the synthesis of antibodies to vaccine EV fraction I and hemagglutinins}; Iordanova AI et al.; Multifactor analysis of the lomefloxacin effect on the primary immune response to T-independent bacterial antigen (vaccine EV fraction 1) and to T-dependent cellular antigen (SRBC) in mice was performed with the use of a wide range of the antibiotic concentrations and the dosage time . It was shown that lomefloxacin in the doses corresponding to the average therapeutic ones used for 3-9 days had no effect on the content of the IgG antibodies, was able to increase the level of the IgM antibodies and insignificantly lowered the concentration of the IgA antibodies. J Neurol, 1996 Apr, 243(4), 315 - 7 MRI detection of epidural spinal abscesses at noncontiguous sites; Pfister HW et al.; We report the cases of two patients with the very uncommon clinical finding of two noncontiguous spinal epidural abscesses, which were located in the cervical and lumbar spine . In each case the diagnosis of the second spinal abscess was made by MRI only after the appearance of a new neurological deficit . Decompressive spinal surgery and intravenous antibiotic therapy led to complete recovery in one patient; the other patient was moderately disabled . As epidural spinal abscesses can occur at noncontiguous sites, MRI of the entire spine may be necessary in selected cases. Mil Med, 1996 Apr, 161(4), 197 - 9 A prospective study of Helicobacter pylori nonulcer dyspepsia; Velanovich V; Helicobacter pylori has been recognized as a contributing factor in gastrointestinal disease . A prospective study was done to evaluate the treatment response of H . pylori nonulcer dyspepsia versus H . pylori-associated gastroduodenal ulcer . Eighty patients were prospectively studied with esophagogastroduodenoscopy . The presence of H . pylori was determined by biopsy . Treatment for H . pylori was amoxicillin, metronidazole, and colloid bismuth with an anti-secretory drug . H . pylori was eradicated in 78.9% of patients . Eighty percent of patients with nonulcer dyspepsia symptomatically improved, compared to 100% of ulcer patients (p = 0.037) . Using stepwise logistic regression, H . pylori eradication was an independent predictor of symptomatic improvement . Therefore, this antibiotic regimen was less likely to lead to improvement in patients with nonulcer dyspepsia; however, patients in whom the organism could be eradicated were more likely to benefit. J Am Podiatr Med Assoc, 1996 Apr, 86(4), 179 - 82 Rheumatoid nodules affecting both heels with surgical debulking: a case report*; Jones RO et al.; The presence of subcutaneous nodules in association with rheumatoid arthritis is well documented . In most cases, these nodules occur in association with severe rheumatoid disease . Treatment should be initiated with conservative measures such as custom-molded shoes, nonweightbearing, and oral antibiotic therapy to control infection . The goals of surgery were to alleviate pain, improve function and cosmesis, remove infected bone, and prevent further infection . The surgical sites are completely healed without complications 2 years postoperatively. J Pharm Sci, 1996 Apr, 85(4), 369 - 72 Determination of free extracellular concentrations of piperacillin by microdialysis; Nolting A et al.; The tissue penetration and distribution of antibiotics is of great importance, since most of the infections occur in the tissue . At the infection site, the free, unbound fraction of the antibiotic is responsible for the antiinfective effect . These free extracellular concentrations can be measured by microdialysis . It was the aim of the study to correlate free levels of the beta-lactam antibiotic piperacillin in blood with those in tissue . In vivo microdialysis sampling was used to study the tissue distribution patterns of piperacillin in anesthetized rats after single dose iv administration of the drug . The pharmacokinetics of piperacillin in plasma were consistent with a two-compartment body model . Comparisons between calculated free concentrations in the peripheral compartment and measured free extracellular concentrations revealed excellent agreement . Microdialysis is a suitable method to evaluate unbound drug concentrations in the tissues . In case of piperacillin, predictions of the concentration time profiles of free drug in the peripheral compartment can be made on the basis of plasma data. Dis Colon Rectum, 1996 Apr, 39(4), 369 - 73 Inpatient vs . outpatient bowel preparation for elective colorectal surgery; Lee EC et al.; BACKGROUND: Recent pressures to decrease the cost of medical care have mandated preoperative outpatient bowel preparation (OBP) for elective colorectal surgery without any data documenting equivalent quality of care . This study examined the safety and efficacy of OBP compared with inpatient bowel preparation (IBP) . METHODS: Records of all patients who underwent OBP for elective colorectal resection since the inception of the OBP program from July 1993 to June 1994 were compared with records of all patients who received IBP for elective procedures from January to June 1993 . RESULTS: The two groups, 90 patients who underwent OBP and 98 patients who had IBP, were well matched for age, sex, diagnosis, and operations performed . The OBP group had a shorter length of hospital stay (median, 7 vs . 9 days; P < 0.0001; chi-squared analysis), whereas the complication rate was similar (19 percent in the OBP group vs . 18 percent in the IBP group), including infectious complications (10 percent in the OBP group vs . 7 percent in the IBP group) . Although operating time was similar (mean, 199 vs . 213 minutes) and estimated blood loss (mean, 528 vs . 536 ml), the OBP group had significantly higher perioperative fluid requirements: intraoperative fluids (median, 4300 vs . 3700 ml; P < 0.05; Student's t-test), intraoperative colloid administration (48 vs . 29 percent; P < 0.0002; chi-squared), 24-hour postoperative fluids (3224 vs . 2700 ml; P < 0.0001; Student's t-test), and postoperative fluid challenges (50 vs . 20 percent; P < 0.0001; chi-squared analysis) . CONCLUSION: Outpatient bowel preparation for elective colorectal surgery is safe and effective . It offers shorter hospital stay, and, therefore, potentially reduces medical care cost . Patients with multiple medical problems may not tolerate extensive fluid shifts; therefore, other preoperative arrangements, such as inpatient or outpatient intravenous fluid therapy, need to be considered to minimize complications that may outweigh potential cost savings. Pigment Cell Res, 1996 Apr, 9(2), 58 - 62 Effective elimination of fibroblasts in cultures of melanocytes by lowering calcium concentration in TPA depleted medium following geneticin treatment; Horikawa T et al.; Melanocytes grow well in culture media supplemented with phorbol ester . However, phorbol ester is metabolically stable and has prolonged effects on multiple cellular responses . Different groups have reported that they could cultivate melanocytes without phorbol ester . However, in medium without phorbol esters contaminating fibroblasts are often difficult to eliminate . We have developed an improved method of eliminating fibroblasts using geneticin in serum free medium with bFGF, endothelin-1 and no phorbol ester . Treatment with a low concentration of geneticin effectively eliminated contaminating fibroblasts and was not harmful to melanocytes if geneticin was added initially in a high calcium media (2 mM) followed by a change to a low (0.09 mM) calcium media immediately after removal of the geneticin . With this technique we could easily establish pure melanocyte culture . This culture method will provide a useful tool for studies on melanocyte cellular response without the influence of phorbol ester. An Esp Pediatr, 1996 Apr, 44(4), 329 - 31 {Acute mastoiditis in childhood . A study of 15 cases}; del Castillo Martin F et al.; We present 15 cases of acute mastoiditis diagnosed in previously healthy children . Diagnostic criteria were the presence of acute otitis media, retroauricular inflammatory signs and radiographic alteration of the mastoid bone . The average age of the children was 3 years, with a range between 5 months and 7 years . Two children were younger than 1 year of age . The lesion was unilateral in all cases . Blood analysis revealed an increased erythrocyte sedimentation rate, being higher than 66 mm in the first hour in all patients . In 4 children it was higher than 110 mm . Ten children received previous antibiotic therapy for acute otitis media and five children did not . Among these 10 treated children, antibiotic therapy was unsuitable in 3 cases . All patients were treated on admission with i.v . antibiotic therapy . Tympanostomy was performed in 5 of 6 cases with the entire eardrum . Mastoidectomy was performed in 3 patients due to poor results of the treatment . The evolution was successful in all cases. Pacing Clin Electrophysiol, 1996 Apr, 19(4 Pt 1), 437 - 42 Salvage of infected ICDs: management without removal; Lee JH et al.; During the 7-year period from August 1986 to December 1993, 242 patients with malignant ventricular arrhythmias underwent 242 ICD implantations and 50 subcutaneous generator changes . Wound infections developed in 5 patients (1.7%): in 3 cases, after primary implantation (3/242 {1.2%}); and in 2 following a generator change (2/50 {4.0%}) . This difference was not statistically significant . Infection developed at the generator pocket and became clinically manifest between 6 weeks and 40 months, postoperatively . Our treatment approach with the first patient consisted of simple debridement of the pocket and reimplantation of the existing generator . This led to recurrence, and the generator was safely explanted . In the remaining four patients, our approach has been that of local treatment, with wide debridement of the pocket, and placement of a closed irrigation system with continuous irrigation with a bacitracin, polymyxin, neomycin solution, and culture-specific antibiotic therapy . We have successfully controlled the infection and salvaged the generator with this approach in all four patients, who are all alive and well at a mean follow-up of 25.0 +/- 17.3 months with no recurrence . The good results obtained in these patients suggest that the concept of total explanation of the infected ICD should be reassessed. Can Vet J, 1996 Apr, 37(4), 222 - 5 Use of ketoprofen as an antipyretic in cats; Glew A et al.; The antipyretic effectiveness of Ketoprofen, a non-steroidal anti-inflammatory drug, was investigated in pyretic cats with a variety of bacterial and viral infections . Cats were randomly assigned to receive either a broad-spectrum antibiotic or a broad-spectrum antibiotic plus ketoprofen . Body temperature was monitored 3 times daily, and attitude and appetite were evaluated once daily . The treatment groups were compared with respect to mean body temperatures, using a one-way analysis of variance . Mean temperatures were significantly different (P < 0.05) during the 4 and 8 h post-treatment observations, with a reduction to normal temperatures in the ketoprofen group compared with no change in the group treated with antibiotics alone . The antipyretic effect of ketoprofen was rapid and persisted for at least 8 h, but for less than 24 h . The overall recovery period from pyrexia, depression, and inappetance was also shorter in cats treated with antibiotics and ketoprofen (3 d) than in cats treated only with antibiotics (5 d) . Ketoprofen was a useful adjunct in the treatment of pyretic cats. Nucl Med Commun, 1996 Apr, 17(4), 311 - 6 Immunoscintigraphy for the detection of brain abscesses; Sandrock D et al.; The aim of this prospective study was to assess the diagnostic usefulness of a 99Tcm-anti-granulocyte antibody in the early differentiation of the aetiology of a ring-enhancing structure on computed tomography (CT) scans following neurosurgical intervention . In 26 patients (15 males, 11 females) aged 20-82 years with suspected intracranial infection, 29 SPET scans of the head were obtained 4-6 h following the intravenous injection of 555 MBq 99Tcm-anti-granulocyte antibody . The patients had antibiotic, antimycotic or corticosteroid therapy . The diagnosis was confirmed by surgery (19 cases) or subsequent CT/MRI (magnetic resonance imaging) scans and clinical follow-up (10 cases) . The immunoscan was true-positive (abscess) in 6 (sensitivity = 100%), true-negative in 19 and false-positive in 4 (specificity 83%) cases . There was no obvious detrimental effect on the results due to the antibiotic, antimycotic or corticosteroid therapy . In conclusion, despite false-positive results, the 99Tcm-anti-granulocyte antibody is a useful tool in the early detection and exclusion of intracranial abscess after neurosurgical interventions. Physiol Behav, 1996 Apr-May, 59(4-5), 915 - 20 Omega-3 fatty acids in boys with behavior, learning, and health problems; Stevens LJ et al.; The purpose of the study reported here was to compare behavior, learning, and health problems in boys ages 6 to 12 with lower plasma phospholipid total omega-3 or total omega-6 fatty acid levels with those boys with higher levels of these fatty acids . A greater frequency of symptoms indicative of essential fatty acid deficiency was reported by the parents of subjects with lower plasma omega-3 or omega-6 fatty acid concentrations than those with higher levels . A greater number of behavior problems, assessed by the Conners' Rating Scale, temper tantrums, and sleep problems were reported in subjects with lower total omega-3 fatty acid concentrations . Additionally, more learning and health problems were found in subjects with lower total omega-3 fatty acid concentrations . (Only more colds and more antibiotic use were reported by those subjects with lower total omega-6 fatty acids) . These findings are discussed in relation to recent findings for omega-3 experimentally deprived animals. J Dairy Sci, 1996 Apr, 79(4), 536 - 42 Effects of media, serum, oviductal cells, and hormones during maturation on bovine embryo development in vitro; Gliedt DW et al.; Our objective was to optimize in vitro maturation conditions of bovine oocytes as assessed by embryo development . In Experiment 1, cumulus-oocyte complexes were matured in either M-199 or RPMI-1640 . Each medium was supplemented with an antibiotic-antimycotic solution (1%) and estrous cow serum (20%) . Cumulus cell expansion after 24 h was greatest for cumulus-oocyte complexes matured in RPMI-1640 . Morulae development on d 7 was greater (21.1%) for oocytes matured in M-199 than for oocytes that matured in RPMI-1640 (9.6%) . In Experiment 2, cumulus-oocyte complexes were matured in M-199 supplemented with antibiotic-antimycotic solution (1%) . Main effects were serum type (20%; estrous cow serum vs . superstimulated estrous cow serum) and coculture (with or without bovine oviductal epithelial cells) . The percentage of oocytes developing into blastocysts (d 9) was higher for oocytes matured in estrous cow serum regardless of coculture . In Experiment 3, effects of estradiol-17 beta (0, 1, and 2 micrograms/ml) and equine LH (0, 10, 20, and 30 micrograms/ml) on cumulus cell expansion and development after fertilization were determined . Cumulus cell expansion and blastocyst development decreased with estradiol-17 beta in the maturation medium, but LH in the medium enhanced expansion of cumulus cells and blastocyst development. J Dairy Sci, 1996 Apr, 79(4), 532 - 5 Effects of oocyte maturation length, sperm capacitation time, and heparin on bovine embryo development; Gliedt DW et al.; This study examined the effects of extending oocyte maturation 4 h beyond current methods and capacitating sperm with or without heparin 4 h before oocyte introduction to determine whether embryo development would increase after in vitro fertilization . Oocytes were aspirated from ovaries that were collected at slaughter . Cumulus-enclosed oocytes were matured in M-199 supplemented with serum from cows in standing estrus (20%), antibiotic-antimycotic solution (1%), HEPES (10 mM), and equine LH (30 micrograms/ml) in a humidified 5% CO2 atmosphere . Oocytes were matured for either 24 or 28 h and subsequently fertilized with sperm that had been capacitated 0 or 4 h (before oocyte contact) with or without heparin (0.2 microgram/ml) . Data were analyzed as a 2 x 2 x 2 factorial design . Percentages of cleavage and development were transformed by the arcsin square root method before analysis of variance . An interaction of maturation length and sperm capacitation resulted because cleavage rate decreased with precapacitated sperm, but only within the 24-h maturation period . Heparin increased cleavage rate at 48 h after fertilization but did not affect further development . More oocytes developed to morulae when they matured for 24 h than when they matured for 28 h . In conclusion, a 24-h maturation length without precapacitated sperm was optimal for the subsequent development of cumulus-oocyte complexes. Antonie Van Leeuwenhoek, 1996 Apr, 69(3), 243 - 56 Techniques for genetic engineering in mycobacteria . Alternative host strains, DNA-transfer systems and vectors; Hermans J et al.; The study of mycobacterial genetics has experienced quick technical developments in the past ten years, despite a relatively slow start, caused by difficulties in accessing these recalcitrant species . The study of mycobacterial pathogenesis is important in the development of new ways of treating tuberculosis and leprosy, now that the emergence of antibiotic-resistant strains has reduced the effectiveness of current therapies . The tuberculosis vaccine strain M . bovis BCG might be used as a vector for multivalent vaccination . Also, non-pathogenic mycobacterial strains have many possible biotechnological applications . After giving a historical overview of methods and techniques, we will discuss recent developments in the search for alternative host strains and DNA transfer systems . Special attention will be given to the development of vectors and techniques for stabilizing foreign DNA in mycobacteria. Exp Brain Res, 1996 Apr, 109(1), 9 - 16 The efferent-mediated suppression of otoacoustic emissions in awake guinea pigs and its reversible blockage by gentamicin; Avan P et al.; The physiology of the medial efferent olivocochlear system involves suppressive interactions of contralateral sounds on ipsilateral sound-evoked responses, but its role is largely unknown to date . Medial efferents act at the level of cochlear outer hair cells via cholinergic synapses and might affect their mechanical activity, thereby modulating auditory sensitivity . The aim of the present work was to obtain noninvasive measurements of distortion-product otoacoustic emissions (DPOEs), which reflect outer hair cell function, in order to establish the characteristics of medial efferent-induced suppression in awake, restrained guinea pigs . A clear suppression of DPOEs was induced by continuous contralateral white noise presented at 20-70 dB SPL, in the absence of any confounding effect of anesthesia, middle-ear muscles, or acoustic cross talk . Recently, acute injection of a high dose of the aminoglycoside antibiotic gentamicin (150 mg/kg) was reported to alter the suppressive effect of contralateral noise on eighth nerve-compound action potentials,