Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer.

PURPOSE: We studied the safety, tolerability and pharmacokinetics of a single immediate post-transurethral resection intravesical instillation of apaziquone for patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Patients with cTa-T1, G1-G2 urothelial cell carcinoma of the bladder underwent transurethral resection of bladder tumor(s) followed by a single intravesical instillation of apaziquone 4 mg/40 ml for 1 hour within 6 hours of transurethral bladder tumor resection. Adverse events and safety parameters were assessed on days 8 and 15 after transurethral bladder tumor resection. Blood samples were drawn before and during the instillation for pharmacokinetic analyses. The first 10 patients with pTa-T1, G1-G2 nonmuscle invasive bladder cancer were also evaluated by cystoscopy 3 months after treatment to determine mucosal healing. RESULTS: Of 20 patients receiving apaziquone 13 (65%) reported 35 adverse events, mostly grade 1 to 2. Eight patients (40%) reported 13 adverse events related to treatment, in particular dysuria, hematuria, bladder spasm, abdominal pain, asthenia and postoperative urinary retention. Three grade 3 and 1 grade 4 event(s) occurred, but these were considered unrelated to treatment. No other significant clinical changes were observed. Apaziquone and the active metabolite EO5a were not detected with pharmacokinetic analyses at any point of time. After 3 months no evidence of impaired mucosal healing was observed. CONCLUSIONS: A single immediate post-transurethral bladder tumor resection instillation of apaziquone was well tolerated with an expected good safety profile. Apaziquone and its metabolite EO5a were not detected systemically with pharmacokinetic analyses. These results have lead to further study of a single immediate instillation of apaziquone.

Challenges in the diagnosis and management of Nocardia infections in lung transplant recipients.

BACKGROUND: Nocardia infection occurs in 2.1-3.5% of lung transplant recipients, and may involve cavitary nodular pulmonary lesions, soft tissue infection, or other sites of dissemination. Nocardiosis can pose challenging clinical problems in the areas of diagnosis and treatment. Diagnostic delays may occur, and adverse reactions to therapy are common. This study reviews clinical and epidemiological aspects of nocardiosis in lung transplant recipients, with special attention to pitfalls in management. Clinicians should be alert for these possibilities in order to institute prompt therapy and to achieve successful outcomes. METHODS: A retrospective cohort study was conducted of 577 lung transplant recipients from January 1991 to May 2007. Demographics, reason for transplant, recent rejection, time from transplantation, site of infection, hypogammaglobulinemia, and/or neutropenia shortly before onset, Pneumocystis jiroveci prophylaxis, Nocardia species, radiographic findings, extrapulmonary lesions, nature and duration of treatment, adverse reactions, and outcomes were recorded. RESULT: Nocardia infection occurred in 1.9% (11/577). Mean onset was 14.3 months after transplant (range 1.5-39 months). N. asteroides was isolated in 55% (6/11). Emphysema was the most common reason for transplant (7/11, 64%). Six patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis. Three patients had immune globulin G levels <400 mg/dL and 2 were neutropenic in the 3 months preceding diagnosis. Diagnosis was made by bronchoalveolar lavage (55%), skin abscess culture (18%), open lung biopsy (9%), pleural fluid (9%), and sputum culture (9%). Definitive diagnosis required a median of 9 days and a mean of 13.6 days (range 3-35 days) from the time of diagnostic sampling. Soft tissue lesions occurred in 3 and central nervous system involvement in 1 patient. Adverse reactions to therapy occurred in 9/10 (90%) of patients for whom information was available. Nocardia-related mortality occurred in 2/11 patients (18%). CONCLUSIONS: Nocardiosis occurred in 1.9% of lung transplant recipients and was associated with a mean of nearly 2 weeks to diagnosis and frequent adverse effects on therapy. TMP-SMX prophylaxis on a thrice weekly basis did not prevent all episodes of nocardiosis. Despite utilization of protocol bronchoscopies with cultures for Nocardia, this organism remains a source of clinical complexity in the lung transplant population.

Laparoscopic seromyotomy (auto-augmentation) for non-neurogenic neurogenic bladder in a child: initial case report.

An eight-year-old boy with lifelong urinary incontinence secondary to non-neurogenic neurogenic bladder underwent successful laparoscopic seromyotomy (auto-augmentation) with resultant cure of his incontinence. The ability to perform this laparoscopically with its seventy-minute operating time, decreased hospital stay, and improved cosmesis militates for its consideration before a standard augmentation is performed.

Laparoscopic vesicoureteroplasty in children: initial case reports.

OBJECTIVE: To determine the feasibility of performing laparoscopic vesicoureteroplasty in children. METHODS: Two pediatric patients, a two-year-old boy and a five-year-old girl, underwent laparoscopic vesicoureteroplasty for vesicoureteral reflux. Operating time was two hours fifteen minutes and three hours fifteen minutes, respectively. RESULTS: The reflux was successfully corrected without morbidity, and they required only short hospitalization (23 hours) and exhibited decreased peri- and post-operative pain as well as improved cosmesis. CONCLUSIONS: These cases represent the first implementation of this technique in humans. We stress that this is a preliminary report and suggest that this technique deserves further study.

Steps toward knowledge-based machine translation.

This paper considers the possibilities for knowledge-based automatic text translation in the light of recent advances in artificial intelligence. It is argued that competent translation requires some reasonable depth of understanding of the source text, and, in particular, access to detailed contextual information. The following machine translation paradigm is proposed. First, the source text is analyzed and mapped into a language-free conceptual representation. Inference mechanisms then apply contextual world knowledge to augment the representation in various ways, adding information about items that were only implicit in the input text. Finally, a natural-language generator maps appropriate sections of the language-free representation into the target language. We discuss several difficult translation problems from this viewpoint with examples of English-to-Spanish and English-to-Russian translations; and illustrate possible solutions as embodied in a computer understander called SAM, which reads certain kinds of newspaper stories, then summarizes or paraphrases them in a variety of languages.

[Lipid peroxidation in a kidney tissue homogenate from rats under heat-induced ischemia with and without glucocorticoid protection]. / Perekisnoe okislenie lipidov v gomogenate pochechnoi tkani krys pri teplovoi ishemii bez i s protektsiei gliukokortikoidami.

Lipid peroxidation (LPO) was investigated in cortical layer homogenates from 56 rat kidneys, intact or exposed to a 30-minute heat ischemia performed without any protection or after a preliminary administration of prednisolone alone or in combination with methypred. Prednisolone was administered i.m. in a dose of 30 mg/kg 2 hrs before and the same dosage of methypred a day before the onset of the experiment. Homogenates were studied both for the initial levels of malonic dialdehyde (MDA) and for the MDA formation in the presence of LPO which was activated in the phosphate buffer by pH 6.8 ascorbate (5.10(-4) M) 5, 10, 15, 20, 25 and 30 minutes after the incubation. The results obtained demonstrated that versus the intact kidneys, in the kidneys exposed to a 30-minute treatment with heat ischemia there were increased levels of initial MDA in the renal tissue, a dramatic increment of its formation during the incubation of homogenate with ascorbate. Shifts in the kinetic curves in homogenates from ischemic kidneys were noted as well. A more dramatic rise (versus intact kidneys) in the MDA formation levels in the presence of LPO observed at the initial stage of the incubation was suggestive of an exhaustive effect of heat ischemia on the system of endogenous antioxidants. The dramatic increment of MDA levels was recorded during a 30-minute incubation. Administration of prednisolone alone or in combination with methypred resulted in a significant inhibition of LPO in ischemic renal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous endoscopic implantation of Automatic Implantable Cardioverter/Defibrillator (AICD): an animal study of a new nonthoracotomy technique.

The Automatic Implantable Cardioverter/Defibrillator (AICD) prevents death due to malignant ventricular arrhythmias but requires thoracotomy for the implantation of the preferred two-patch lead system. The purpose of this study was to develop and test a new percutaneous endoscopic method of the AICD lead implantation without the need for open chest surgery. A high resolution video endoscopy system and currently available endoscopic instrumentation were used to develop pleural-pericardial dissection technique in 7 pigs and to endoscopically implant custom-made AICD patches in 20 pigs. An examining 10 mm rigid endoscope inserted in the 6th intercostal space in the anterior axillary line provided direct visual control for endoscopic dissection of the parietal pleura from the pericardium, delivery, and implantation of the AICD patches. This was successfully carried out through two trocars (10 and 11 mm) inserted into the pleural-pericardial space via the subxyphoid approach in 18 of 20 pigs. Effective patch positioning was confirmed by attaining a defibrillation threshold of 20J or less in 13 pigs. Of those, three required lead polarity reversal, and three others required lead repositioning to lower defibrillation thresholds to 20J or less. In three pigs, defibrillation thresholds of 30J or higher were required. Defibrillation was unsuccessful in two pigs due to patch malfunction. The authors conclude that percutaneous endoscopy is a feasible method of AICD lead implantation.

Laparoscopic renal surgery in children.

A total of 17 laparoscopic renal procedures was performed in children, including nephrectomy (10), nephroureterectomy (4), partial nephrectomy (2) and giant renal cyst excision (1). Patient age ranged from 4 months to 11 years (average age 34 months). The average operating time was 2 hours and 15 minutes, ranging from 1 hour 50 minutes to 2 hours 45 minutes. The usual period of hospitalization was 23 hours, with the longest being 36 hours for 2 patients. No complications ensued. Despite the decreased working space in children, laparoscopic renal surgery offers compelling advantages, including short hospitalization, less perioperative and postoperative pain, improved cosmesis, earlier return to normal unrestricted activities and early return to work for the parents. Methods to accomplish renal laparoscopic surgery safely in children are detailed.

Laparoscopic cholecystectomy: instrumentation and technique.

Laparoscopic cholecystectomy is rapidly evolving as a therapeutic modality for the treatment of gallstone disease. The technical details of this procedure and the method by which the gallbladder is dissected and removed are critical to the safe, effective execution of the procedure. Our technique has been developed through extensive practice in porcine models and through experience with more than 250 patients. To perform laparoscopic cholecystectomy we employ a high-resolution video endoscopy system, two high-resolution color monitors, a high-flow CO2 insufflator, a 300 W Xenon light source, electrocautery and/or lasers, and an endoscopic suction-irrigation system. This equipment permits the surgeon to obtain a clear field of view within the abdomen. With these tools, appropriately designed for laparoscopic surgery, including a laparoscope, graspers, dissectors, cholangiography equipment, scissors, and clip appliers, the surgeon can remove the gallbladder without opening the abdomen. The procedure requires the induction of a CO2 pneumoperitoneum, insertion of four trocars, and placement of a grasping retractor to set the operative field. An additional retractor placed on Hartmann's pouch provides countertraction for dissection of the hilum. Careful dissection around the cystic duct and cystic artery with a combination of electrocautery and blunt dissection allows the surgeon to skeletonize the cystic duct and artery. After intraoperative cholangiography confirms the anatomy, the cystic artery and cystic duct are clipped and divided. Electrocautery or laser techniques can be used to perform retrograde dissection of the gallbladder from the liver bed and insure hemostasis. The gallbladder is detached and removed intact through the large trocars. This basic technique can be applied in a wide variety of patients with cholelithiasis. The surgeon proficient in this technique may apply it to a broad range of patients with gallbladder disease.

Laparoscopic choledochoscopy: an effective approach to the common duct.

With increasing acceptance of routine cholangiography during laparoscopic cholecystectomy (for confirmation of anatomy) there has been increased identification of common duct calculi. A technique of laparoscopic transcystic common duct stone extraction is described and early clinical results are presented. Successful stone extraction was accomplished in 39 out of 41 consecutive attempts by one surgical team. Two cases required choledochotomy. There were four complications including hyperamylasemia (2), minor wound infection (1), and incidental pneumothorax (1). Recommendations regarding safety and indications are presented. Initial evaluation suggests laparoscopic transcystic stone extraction is safe and effective.

[Are the sequelae predictable for sectional and multiple partial nephrolithotomies of completely intrarenal coral stones? (experimental and clinical research)]. / Predskazuemy li posledstviia sektsionnoi i mnozhestvennykh partsial'nykh nefrolitotomii po povodu polnost'iu vnutripochechnykh korallovidnykh kamnei? (éksperimental'no-klinicheskoe issledovanie).

In the assessment of surgical intervention for fully intrarenal stone casts, different kinds of nephrotomies (sectional or multiple partial ones, those supplementing pyelolithotomy or performed in the kidneys with marked parenchyma) should be compared in terms of functional outcomes, severity and incidence of complications (intraoperative or postoperative bleeding from the violated kidney), postoperative urinary fistulas, aggravated renal failure and postoperative mortality. It is these milestones that have determined the scope of the present study. An experimental assessment of the degree of trauma, associated with sectional nephrolithotomy as well as its functional sequelae was made in dogs after a stone-like structure was simulated and the kidney reached the necessary degree of secretory deficiency. The comparison of pre- and postoperative renographic parameters over different spans of follow-up of animals after sectional nephrolithotomy was made to assess the latter's organ-damaging effect and, in part, functional results of surgery in a kidney with a profound functional deficiency by the time of the operation. A similar methodology was used in clinical patients, subjected to nephrolithotomy (either sectional or multiple partial procedure) for fully intrarenal coral stones. Functional results of nephrolithotomies in animals and in patients are presented in Figs 1-3. For cases where postoperative results were good or satisfactory at 1-2 months, follow-up results are presented in Tables 4-5. Postoperative complications of sectional and partial nephrolithotomies are reflected in Figs. 4-5. The incidence of paranephritis and postoperative mortality are reported in Tables 6-7. Therefore, functional results of sectional nephrolithotomy are indicative of its considerable organ-sparing effect in experimental animals. Functional outcomes of the clinical sectional and multiple partial nephrolithotomies are similar, yet partial nephrolithotomies are more detrimental to the kidney and the upper urinary tract in terms of the pattern and rate of postoperative complications, as compared to sectional nephrolithotomy. As the sequelae of sectional and partial nephrolithotomies are largely unpredictable, indications for surgical removal of intrarenal stereometrically-composite coral stones should be as limited as possible.