Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods.

Antifungal susceptibility testing of Aspergillus species has been standardized by both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recent studies suggest the emergence of strains of Aspergillus fumigatus with acquired resistance to azoles. The mechanisms of resistance involve mutations in the cyp51A (sterol demethylase) gene, and patterns of azole cross-resistance have been linked to specific mutations. Studies using the EUCAST broth microdilution (BMD) method have defined wild-type (WT) MIC distributions, epidemiological cutoff values (ECVs), and cross-resistance among the azoles. We tested a collection of 637 clinical isolates of A. fumigatus for which itraconazole MICs were < or = 2 microg/ml against posaconazole and voriconazole using the CLSI BMD method. An ECV of < or = 1 microg/ml encompassed the WT population of A. fumigatus for itraconazole and voriconazole, whereas an ECV of < or = 0.25 microg/ml was established for posaconazole. Our results demonstrate that the WT distribution and ECVs for A. fumigatus and the mold-active triazoles were the same when determined by the CLSI or the EUCAST BMD method. A collection of 43 isolates for which itraconazole MICs fell outside of the ECV were used to assess cross-resistance. Cross-resistance between itraconazole and posaconazole was seen for 53.5% of the isolates, whereas cross-resistance between itraconazole and voriconazole was apparent in only 7% of the isolates. The establishment of the WT MIC distribution and ECVs for the azoles and A. fumigatus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.

Dilatation of bronchial stenosis with Gruentzig balloon.

Current treatments for bronchial stenosis include surgical resection, laser photoresections, cryotherapy, and limited experience with balloon dilatation. This article describes the use of the Gruentzig balloon for treatment of an acquired bronchial anastomotic stricture after sleeve resection for carcinoma.

Absence of a pharmacokinetic interaction between intravenous theophylline and orally administered levofloxacin.

A randomized, placebo-controlled, two-way crossover study in 16 healthy men was performed to determine the effect of orally administered levofloxacin at steady-state conditions, given at 500 mg every 12 hours, on the pharmacokinetics of theophylline given as a single 4.5-mg/kg intravenous infusion. Participants were assigned randomly to receive theophylline with levofloxacin in one study period and theophylline with placebo in the other period. Fourteen individuals completed the study. Mean (+/-SD) values for theophylline pharmacokinetic parameters for the levofloxacin and placebo treatments, respectively, were peak plasma concentrations (Cmax) of 11.4 (1.8) micrograms/mL and 10.7 (1.3) micrograms/mL; areas under the concentration time curve from time 0 extrapolated to infinity (AUCzero-infinity) of 124 (32) micrograms.hr/mL and 126 (30) micrograms.hr/mL; volumes of distribution at steady state (Vdss) 31.7 (3.5) L and 32.0 (3.9) L; clearances (Cl) of 48.6 (11.6) mL/min and 47.4 (10.3) mL/min; and half-lives (t1/2) of 8.1 (1.9) hours and 8.2 (1.8) hours. There were no statistically significant differences between treatments for any of these parameters. There was no pharmacokinetic interaction between levofloxacin administered orally at steady-state conditions and intravenously administered theophylline.

Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis.

OBJECTIVES: To evaluate, in two randomized, multicenter trials, levofloxacin compared with ciprofloxacin and lomefloxacin for efficacy and safety in treating acute pyelonephritis. METHODS: We enrolled a total of 186 patients with bacteriologically proved infection. Of these, 89 patients in both trials combined received levofloxacin 250 mg once daily; 58 received ciprofloxacin 500 mg twice daily in the first trial (double blind); and 39 received lomefloxacin 400 mg once daily in the second trial (open label). Microbiologic response of patients evaluable for microbiologic efficacy was the primary efficacy variable, and clinical response of microbiologically evaluable patients was the secondary efficacy variable in both studies. RESULTS: Escherichia coli was the most prevalent pathogen. At 5 to 9 days after the end of treatment, 95% of uropathogens were eradicated in patients who received levofloxacin compared with 94% in the ciprofloxacin-treated group and 95% in the lomefloxacin-treated group. The clinical cure rate was 92% for levofloxacin in both studies combined, 88% for ciprofloxacin, and 80% for lomefloxacin. Drug-related adverse events were reported by 2% of levofloxacin-treated patients, 8% of ciprofloxacin-treated patients, and 5% of lomefloxacin-treated patients. CONCLUSIONS: The once-daily oral administration, proven efficacy, and good tolerability make levofloxacin an excellent choice for empiric treatment of acute pyelonephritis.

A controlled trial of levofloxacin and lomefloxacin in the treatment of complicated urinary tract infection.

OBJECTIVES: The efficacy and safety of levofloxacin and lomefloxacin in complicated urinary tract infections (UTIs) were compared in a randomized, open-label, multicenter study. METHODS: Outpatients were randomized to receive levofloxacin (250 mg once daily) for 7 to 10 days or lomefloxacin (400 mg once daily) for 14 days. Three hundred thirty-six patients (171 with levofloxacin, 165 with lomefloxacin) were evaluable for microbiologic efficacy, and 461 patients (232 with levofloxacin, 229 with lomefloxacin) for safety. RESULTS: The overall microbiologic eradication rate of pathogens was 95.5% (168 of 176) for levofloxacin and 91.7% (154 of 168) for lomefloxacin. Eradication rates with respect to patients were 95.3% (163 of 171) and 92.1% (152 of 165) for levofloxacin and lomefloxacin, respectively. At the 5 to 9-day post-therapy visit, symptoms were completely resolved in 84.8% of levofloxacin-treated patients and were decreased in 8.2% (93.0% clinical success). Among the lomefloxacin-treated patients, complete resolution was seen in 82.4%, with decreased symptoms in 6.1% (88.5% clinical success). Drug-related adverse events (AEs) were reported by 10 (2.6%) and 18 (5.2%) levofloxacin- and lomefloxacin-treated patients, respectively. Compared with levofloxacin-treated patients, more lomefloxacin-treated patients experienced photosensitivity reactions (3 [1.3%] versus 0) and dizziness (2 [0.9%] versus 0). Nausea (3 [1.3%] versus 1 [0.4%]) was more frequent in the levofloxacin-treated group. Six patients in each treatment group had a gastrointestinal AE (1.7%); rash was reported more frequently with lomefloxacin (4 patients [0.4%]) than with levofloxacin (1 patient [0.4%]). Discontinuation because of AEs was observed in 8 (3.4%) levofloxacin- and 14 (6.1%) lomefloxacin-treated patients. CONCLUSIONS: Once-daily levofloxacin is as effective as and has a superior tolerability profile than lomefloxacin in the treatment of complicated UTIs.

Two new human neuroblastoma cell lines exhibiting tumorigenesis and metastasis in the nude mouse model.

BACKGROUND: Human neuroblastoma cell lines are notoriously difficult to establish in culture and use in murine hosts. MATERIALS AND METHODS: Two new human neuroblastoma cell lines, NK and ND, were established and studied for growth patterns in nude mice, growth in soft agar, cell cycle analysis, apoptosis (Hoechst- merocyanine 540 test), metalloproteinase expression (zymograms), and morphological differentiation by dibutyryl cyclic AMP (dCAMP). RESULTS: Both cell lines formed tumors in 6/9 nude mice within 5-31 days after subcutaneous inoculation, and metastases after intravenous tail vein injection. Both grew in soft agar. DCAMP induced morphologic differentiation in both, and inhibited cell culture growth without apoptosis. Zymograms of supernatants from cultures revealed 72-kDa metalloproteinase and higher molecular bands that did not change with dCAMP treatment. Cultures derived from murine metastatic foci exhibited 72, 82 and 85-kDa proteins, with strong 92-kDa bands after dCAMP treatment. CONCLUSION: New human neuroblastoma cell lines were established that are easily used in nude mice, and express metalloproteinases.

Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults.

In this comparative trial, outpatients with acute sinusitis were randomly assigned to receive levofloxacin (500 mg orally once daily) or amoxicillin-clavulanate (500/125 mg orally 3 times daily) for 10 to 14 days. The success rates (cured and improved) 2 to 5 days after the end of treatment were 88.4% for the 267 clinically evaluable patients who received levofloxacin and 87.3% for the 268 clinically evaluable patients who received amoxicillin-clavulanate. Drug-related adverse events occurred in a smaller percentage of patients in the levofloxacin treatment group (7.4%) than in the amoxicillin-clavulanate treatment group (21.2%). The most common of these were nausea, diarrhea, vaginitis, and abdominal pain for levofloxacin-treated patients and diarrhea, vaginitis, nausea, genital moniliasis, abdominal pain, vomiting, and flatulence for amoxicillin-clavulanate-treated patients. The results of this study show that once-daily administration of levofloxacin is as effective and better tolerated than amoxicillin-clavulanate administered 3 times daily for treating acute sinusitis in adult outpatients.

Intraabdominal leg: unique variant of split notochord syndrome.

An infant was born with a spectrum of anomalies representing a unique variant of the split notochord syndrome. The major anomalies included giant omphalocele and duplicated lower spine, between which developed a posterior lumbosacral mass that was contiguous with an intraabdominal, skin-covered "leg" within a saccular cecum. Features of this case overlap aspects of fetiform teratoma, fetus-in-fetu, conjoined twins, and caudal duplication, suggesting an etiologic relation between these entities and split notochord syndrome.

New application of endoloop for rectal polypectomy.

The primary difficulty in performing rectal procedures such as polypectomy in children is the limited space in which to suture after a biopsy. Use of an available laparoscopic pretied loop ligature has been adapted to simplify these cases.

Pancreatic anatomy in children: emphasis on its importance to pancreatectomy.

The literature is riddled with misconceptions concerning the landmarks and the actual amount of pancreatic tissue resected in "subtotal" 60% to 90% pancreatectomies. In order to clarify the surgical anatomy of the pancreas, 13 autopsy specimens from children aged 2 days to 15 years were carefully examined. Pancreata were serially removed from the in situ position in four sections and weighed. Section 1 included pancreatic tissue from the tail to the left of the superior mesenteric vessels (SMV); section 2 included all tissue from the tail to the right of the SMV; section 3 contained tissue up to the left of the pancreaticoduodenal vessels in the head of the pancreas; and section 4 included the remainder of the pancreatic head within the duodenal sweep and the uncinate process. Results showed that section 1 weighed 47.5% +/- 9.7% (mean +/- SD) of the total pancreatic weight with a wide range of 32.3% to 67.3%; section 2 weighed 53.5% +/- 9.0% (range, 38.7% to 72.2%); section 3 weighed 69.1% +/- 15.6% (range, 43.5% to 95.8%); and section 4 weighed 31.6% +/- 14.6% (range, 4.2% to 56.5%). As noted, pancreatic anatomy was extremely variable in relation to the percent of tissue to either side of the SMV and the proportion of tissue contained within the uncinate process. Resections historically reported to result in a "75%" pancreatectomy (section 2) were demonstrated to contain a mean of only 53.5% +/- 9.0% of the pancreas. Less tissue than expected would be resected by using the SMV as landmarks for a 75% resection. The wide variation in anatomy also has important clinical implications in performing "subtotal" pancreatectomies in infants with nesidioblastosis in whom the amount of tissue resected is critical to the patient's postoperative clinical course. This study demonstrates that a subtotal pancreatectomy should not be based upon the presumed relation of the pancreatic substance to the SMV. The entire gland including the uncinate process should be visualized at operation in order that a proper pancreatectomy is performed.

Percutaneous dilational tracheostomy in children and teenagers.

Percutaneous dilational tracheostomy (PDT) is a new technique that has been successfully performed in adult patients who required long-term mechanical ventilation, but it has not been used in children. The authors report their initial experience with PDT in 11 children and teenagers. The procedure is as follows. Using Seldinger's technique, the trachea is cannulated with a guide-wire. It is then progressively dilated, to an appropriately sized tract, with dilators from a commercially available kit. Then, a tracheostomy tube can be inserted into the trachea, loaded over a dilator. Eleven children, aged 10 to 20 years, underwent PDT in an average of 20 minutes. In eight cases, PDT was performed at the bedside. One intraoperative and one postoperative complication developed in the same patient; both complications were easily recognized and treated. Tracheal stenosis has not developed in eight decannulated patients at an average of 43 +/- 30 weeks after decannulation. PDT appears to be a safe, potentially cost-effective alternative to open tracheostomy in young patients.

Hemoperitoneum from perforated Meckel's diverticulum.

Approximately 4% of patients with Meckel's diverticulum will experience complication, the most common of which are intestinal obstruction, gastrointestinal bleeding, acute inflammation, and perforation. We report an extremely rare complication of perforated Meckel's diverticulum which presented as hemoperitoneum.

Review of bronchopulmonary foregut malformations.

The term bronchopulmonary foregut malformation (BFM) describes rare cases of pulmonary sequestrations that communicate with the upper gastrointestinal tract. An unusual type of BFM is described; it consisted of esophageal atresia, proximal and distal tracheoesophageal fistulae, and bilateral extralobar pulmonary sequestrations communicating with a common bronchial structure that replaced the distal esophagus. This case is related to other reported cases in the literature, and serves as the basis for a proposed theory of the embryonic development of BFM.

Limy bile syndrome.

Limy bile syndrome (LBS) is a rare condition in which a radiopaque gallbladder and/or bile ducts are noted on plain roentgenograms. LBS is caused by calcium carbonate precipitation in the bile and is usually associated with distal biliary tract obstruction. The etiology of limy bile syndrome is unclear; however, it may be a long-term complication of total parenteral nutrition.

The relationship of class I MHC antigen expression to stage IV-S disease and survival in neuroblastoma.

Cultured human neuroblastoma cells express low levels of class I (MHC) surface antigen. In order to determine if this low expression is representative of the clinical tumor, this study investigates class I expression in archival human neuroblastoma. Whereas stages I to IV neuroblastoma expressed low levels of class I antigen, stage IV-S tumor cells expressed normal levels, similar to control tissues. Expression of class I antigen in tumors from survivors of stage III neuroblastoma was significantly greater than in tumors from nonsurvivors. Tumors comprised predominantly of ganglion cells expressed significantly more class I antigen than neuroblasts. These data suggest that class I MHC expression may play a role in the natural history of human neuroblastoma.

Postoperative immunotherapy of murine C1300-neuroblastoma.

Low-dose cyclophosphamide (CY) is an immunomodulating agent that down-regulates T suppressor cell function. This study investigates postoperative immunotherapy with CY as an alternate treatment for advanced immunogenic tumors such as neuroblastoma that typically respond poorly to traditional high-dose chemotherapy. A/J mice with 1.5-cm subcutaneous C1300-neuroblastoma (C1300-NB) tumors were divided into the following treatment groups: I, untreated (n = 14); II, 85% tumor resection (n = 18); III, sham-operated (n = 18); IV, multiple-dose CY (n = 6); V, 85% resection and single-dose CY (n = 14); VI, 85% resection and multiple-dose CY (n = 14). CY (100 mg/kg, intraperitoneally) was given initially 24 hours post-operatively to groups IV, V, and VI. Groups IV and VI also received weekly maintenance doses of 25 mg/kg CY. Results showed significantly increased survival (log-rank test) in CY-treated groups (IV, V, VI) compared with control groups (I,II,III). Cures were observed only in groups receiving partial resection plus CY (V, 7%; VI, 29%). Although surgical debulking of tumor alone (II) did not enhance survival, the procedure normalized depressed total lymphocyte counts and the subpopulation of Lyt 2,3+ (T suppressor/cytolytic cells) in the immediate postoperative period during which immunotherapy with CY was instigated. This may have contributed to the success of CY immunotherapy. To characterize the tumor-host immune interaction, additional studies were performed. Results showed the following. (1) Mice cured by debulking plus CY (from groups V and VI) could not be successfully reimplanted with C1300-NB, demonstrating immunologic mediation by CY.(ABSTRACT TRUNCATED AT 250 WORDS)

Separation of complex pygopagus conjoined twins.

Pygopagus twins were born with a unique spectrum of anomalies including a conjoined distal spinal cord, single kidney (in twin A), single rectum (in twin A), single vagina (in twin B), and severe central nervous system anomalies in twin B that precluded her independent survival. Separation at 10 weeks of age was tailored toward Twin A's survival. This report discusses the surgical modifications necessary in view of the unique anatomy, including salvaging the distal spinal cord and vagina for twin A.

Combined preoperative and postoperative immunotherapy for murine C1300 neuroblastoma.

Preoperative treatment of murine C1300-neuroblastoma (C1300) with triple immunotherapy using low-dose cyclophosphamide (CY), retinyl palmitate (RP), and interleukin-2 (IL2), followed by tumor resection leads to significant initial tumor control and prolonged survival. However, because long-term tumor recurrence is 67%, the efficacy of continued postoperative immunotherapy is now evaluated. Thirty-two A/J mice with 1 cm subcutaneous C1300 tumors were treated for 13 days with CY-100 mg/kg, intraperitoneally (IP), on day 2 of treatment then 25 mg/kg on day 9, RP-2500 IU IP 2 x/week, and IL2 1.6 x 10(5) U IP BID on days 4 to 9 and 11 to 13. On day 14, mice were divided into five treatment groups: (1) OP (operated-tumor resection, n = 6); (2) OP+CY (resection and postoperative CY, n = 7); (3) OP+CY+RP (resection and postoperative CY+RP, n = 7); (4) OP+CY+RP+IL2 (resection and postoperative CY+RP+IL2, n = 7); and (5) CY+RP+IL2 (continued CY+RP+IL2 with no resection, n = 5). Survival and postoperative tumor recurrence were followed for 60 days. The cure rates were group 1 33% (2/6), group 2 43% (3/7), group 3 29% (2/7), group 4 71% (5/7), and group 5 20% (1/5). After surgery, tumors that recurred did so in 8 to 22 days, with no statistical difference noted between groups. MHC class I antigenic expression of tumors resected on day 14 and recurrent tumors was determined with monoclonal antibodies and flow cytometry. In tumors resected on day 14, class I expression measured by mean fluorescence, was 374.8 +/- 27.40.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced resection and improved survival in murine neuroblastoma (C1300-NB) after preoperative immunotherapy.

Advanced neuroblastoma treated with standard chemotherapy has a poor prognosis. Combination immunotherapy for murine neuroblastoma with retinyl palmitate, low-dose cyclophosphamide, and interleukin-2 resulted in increased survival, impaired tumor growth, easier surgical resection, and increased class I expression or tumor cells. Preoperative immunotherapy may be useful in treatment of advanced human neuroblastoma.

Subclavian artery compression from a chest tube after thoracotomy in a premature infant.

A premature baby underwent thoracotomy for repair of esophageal atresia and tracheoesophageal fistula, during which time a right chest tube was placed. In the immediate postoperative period, right subclavian artery occlusion was recognized and relieved by partial withdrawal of the chest tube, which had migrated high into the apex of the right hemithorax.