Multi-institutional Outcomes and Associations After Excision and Primary Anastomosis for Radiotherapy-associated Bulbomembranous Urethral Stenoses Following Prostate Cancer Treatment.

OBJECTIVE: To evaluate the outcomes of excision and primary anastomosis (EPA) for radiation-associated bulbomembranous stenoses using a multi-institutional analysis. The treatment of radiation-associated urethral stenosis is typically complex owing to the adverse impact of radiation on adjacent tissue. METHODS: An IRB-approved multi-institutional retrospective review was performed on patients who underwent EPA for bulbomembranous urethral stenosis following prostate radiotherapy. Preoperative patient demographics, operative technique, and postoperative outcomes were abstracted from 1/2007-6/2018. Success was defined as voiding per urethra without the need for endoscopic treatment and a minimum follow-up of 12 months. RESULTS: One hundred and thirty-seven patients from 10 centers met study criteria with a mean age of 69.3 years (50-86), stenosis length of 2.3 cm (1-5) and an 86.9% (119/137) success rate at a mean follow-up 32.3 months (12-118). Univariate Cox regression analysis identified increasing patient age (P = .02), stricture length (P <.0001) and combined modality radiotherapy (P = .004) as factors associated with stricture recurrence while body mass index (P = .79), diabetes (P = .93), smoking (P = .62), failed endoscopic treatment (P = .08) and gracilis muscle use (P = .25) were not. On multivariate analysis, increasing patient age (H.R.1.09, 95%CI 1.01-1.16; P = .02) and stenosis length (H.R.2.62, 95%CI 1.49-4.60; P = .001) remained associated with recurrence. Subsequent artificial urinary sphincter was performed in 30 men (21.9%), of which 25 required a transcorporal cuff and 5 developed cuff erosion. CONCLUSIONS: EPA for radiation-associated urethral stenosis effectively provides unobstructed instrumentation-free voiding. However, increasing stenosis length and age are independently associated with surgical failure. Patients should be counseled that further surgery for incontinence may be necessary.

Management of Delayed Onset Postoperative Hemorrhage after Anastomotic Urethroplasty.

Excision with primary anastomosis (EPA) urethroplasty is generally the preferred method for short strictures in the bulbar urethra, given its high success rate and low complication rate compared to other surgical interventions. Bleeding is a presumed risk factor for any surgical procedure but perioperative hemorrhage after an EPA requiring hospitalization and/or reintervention is unreported with no known consensus on the best course for management. Through our experience with three separate cases of significant postoperative urethral hemorrhage after EPA, we developed an algorithm for treatment beginning with conservative management and progressing through endoscopic and open techniques, as well as consideration of embolization by interventional radiology. All the three of these cases were managed successfully though they did require multiple interventions. We theorize that younger patients with more robust corpus spongiosum and more vigorous spontaneous erections, patients that have undergone fewer prior urethral procedures and therefore have more prominent vasculature, and those patients managed with a two-layer closure of the ventral urethra without ligation of the transected bulbar arteries are at a higher risk for this complication.

Projecting the clinical benefits of adjuvant radiotherapy versus observation and selective salvage radiotherapy after radical prostatectomy: a decision analysis.

Our purpose was to project and compare clinical and quality-adjusted life year (QALY) outcomes of adjuvant radiotherapy (ART) versus salvage RT (SRT) after radical prostatectomy for men with locally advanced prostate cancer. We constructed a Markov model to simulate the randomized studies of observation versus ART, assuming 75% of observation patients would receive SRT at PSA recurrence. Transition probabilities and utility inputs were drawn from randomized trials of ART and cohort studies of SRT. We projected 10-year PSA recurrence-free survival, metastasis-free survival and overall survival. We found that observation with selective SRT yielded slightly worse outcomes than ART for post-RT PSA recurrence-free survival (47 and 52%), metastasis-free survival (69 and 70%) and overall survival (72 and 73%). Findings were robust to sensitivity analyses. After adjusting for the disutility of RT, observation plus SRT yielded better QALYs at 10 years than ART (6.80 and 6.13 QALYs). Thus, observation plus SRT may be optimal for men likely to comply with surveillance who wish to minimize side effects of the treatment. These findings reflect outcomes for the average patient given the current level of evidence and are meant to help inform current decision-making as we await future clinical studies of comparative effectiveness.

A case of fatal poisoning with the aconite plant: quantitative analysis in biological fluid.

In recent years recorded cases of plant poisoning have become rare, this may in part be due to the possibility of plant ingestion not being indicated at the beginning of an investigation. Aconitum napellus (aconite, Wolfsbane, Monkshood) is one of the most poisonous plants in the UK. It contains various potent alkaloids such as aconitine, isoaconitine, lycaconitine and napelline. Ingestion of Aconitum plant extracts can result in severe, potentially fatal toxic effects. This paper describes the analytical findings in a recent death in the UK. resulting from deliberate ingestion of Aconitum napellus extract. The concentrations of aconitine measured by HPLC-DAD in the post mortem femoral blood and urine were 10.8 micrograms/L and 264 micrograms/L, respectively. The aconitine concentration in the ante mortem urine was 334 micrograms/L and was estimated to be 6 micrograms/L in the ante mortem serum. Hence, accidental, suicidal or homicidal poisoning due to the ingestion of plant material remains a possibility and should be borne in mind when investigating sudden or unexplained death.

Enteroviral encephalitis leading to a locked-in state.

Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Although enteroviruses are a common cause of community-acquired aseptic meningitis, enteroviral meningitis usually has a benign course. We describe a 14-year-old patient with enteroviral meningoencephalitis diagnosed by polymerase chain reaction. Her level of consciousness declined rapidly after hospital admission and resulted in a locked-in state. Although she experienced slow neurologic improvement, residual neurologic deficits remain. Although there is a general awareness of the characteristics of enteroviralencephalitis, this case report is significant in presenting a case of unusual severity and sequelae. To our knowledge, this is the first published report of an enterovirus encephalitis leading to a locked-in-state.

Office laboratory procedures, office economics, parenting and parent education, and urinary tract infection.

We once again review four areas of interest to office-based pediatricians: office laboratory procedures, office economics, parenting and patient education, and urinary tract infections. Sean Elliott reviews the current status of the Clinical Laboratories Improvement Amendments (CLIA) and their continuing impact on physician office laboratories. Eve Shapiro reviews office economics, this year focusing on managed care, the physician workforce, practice management, and health care financing for the uninsured. Anna Binkiewicz provides an update on parenting and parent education, with recent reports on nutrition and childhood immunizations. Richard Wahl again reviews recent research on urinary tract infection, discussing voiding physiology, dysfunctional voiding patterns, acute urinary retention, urine collection techniques, diagnosis in young infants, and antibiotic prophylaxis.

Staphylococcus lugdunensis: an emerging cause of ventriculoperitoneal shunt infections.

Staphylococcus lugdunensis, a coagulase-negative staphylococcus first described in 1988, has gained recognition as an organism with considerable pathogenic capability in adults. In contrast to the indolent presentation characteristic of other coagulase-negative staphylococci, S. lugdunensis infections resemble the aggressive behavior of Staphylococcus aureus. Although the organism has been isolated from a wide variety of infections in adults, it is a very rare cause of pediatric infections. We describe the first two pediatric patients who developed ventriculoperitoneal shunt infections caused by S. lugdunensis. These cases suggest that coagulase-negative staphylococci should be identified to the species level and that, if S. lugdunensis is identified, greater morbidity compared to that associated with other coagulase-negative staphylococcal shunt infections should be anticipated. A longer course of therapy is recommended for S. lugdunensis infections.

Pilot test of an Internet virtual world chat room for rural teen smokers.

OVERVIEW: This pilot study evaluated the acceptability and efficacy of an Internet-based virtual reality "world" for teen smoking cessation. Rural teens at six school sites interacted in real-time in the virtual world with a trained cessation counselor and other teen smokers over a 2-month period in seven 1-hour chat sessions. The cessation counselor used motivational interviewing, a "client-centered" nonconfrontational approach to behavior change that has shown promise with behaviors resistant to change. Smoking behavior and attitudes were assessed at baseline, after intervention, and at 1-month follow-up. Significant changes were found in quitting, amount smoked, and intentions to quit. Positive trends were seen in past-week abstinence rates, quit attempts, and attitudes toward quitting.

Analysis of 4-methylthioamphetamine in clinical specimens.

There has been much publicity, particularly in Europe, regarding a new phenylethylamine-based compound called 4-methylthioamphetamine (4-MTA), also known as para-methylthioamphetamine (p-MTA), MTA or 'Flatliner'. Chemically, 4-MTA is an amphetamine derivative and is a potent, non-neurotoxic serotonin-releasing agent and reversible inhibitor of rat monoamine oxidase-A. Its effects, therefore, appear different from those of amphetamine. Analysis of various plasma and urine specimens in three clinical cases implicating 'Ecstasy' ingestion revealed the presence of 4-MTA. Presumed metabolites were also detected, with one compound identified as being 4-MTA sulphoxide. The concentrations of 4-MTA measured in the plasma ranged from 0.131 mg/L to 0.760 mg/L. In one patient the 4-MTA concentration was determined in a series of plasma samples and this allowed a presumptive half-life of approximately 7 h to be estimated. This paper describes the first reported data regarding possible pharmacokinetics of 4-MTA in humans and presents the first reported non-fatal instances of 4-MTA intoxication in the UK.

Office laboratory procedures, office economics, parenting and parent education, and urinary tract infection.

We again review four areas of interest to office-based pediatricians: office laboratory procedures, office economics, parenting and patient education, and urinary tract infections. Sean Elliott provides an update on the Clinical Laboratories Improvement Amendments (CLIA) and their impact of office practice. Eve Shapiro reviews office economics, focusing on measuring quality of care, use of performance data, costs of new technologies, and the impact of managed care on the medical marketplace. John Walter offers an update on parenting and parent education, with approaches to counseling families about overuse of antibiotics, teen pregnancy, hyperactivity, violence, and asthma. Richard Wahl reviews the recent research on urinary tract infection, with special attention paid to office diagnosis and management, longitudinal studies of children with urinary tract infections, and the controversy surrounding the American Academy of Pediatrics Task Force on Circumcision report.

Fatal poisoning with a new phenylethylamine: 4-methylthioamphetamine (4-MTA).

There has been much publicity in the United Kingdom regarding a new phenylethylamine-based compound called 4-methylthioamphetamine (4-MTA), also known as para-methylthioamphetamine (p-MTA), MTA or "Flatliner". Chemically, 4-MTA is an amphetamine derivative and is a non-neurotoxic potent serotonin-releasing agent and reversible inhibitor of rat monoamine oxidase-A. Analysis of postmortem blood and urine specimens in a case implicating 3,4-methylenedioxymethamphetamine revealed the presence of 4-MTA at a concentration of 4.6 mg/L in femoral blood and 87.2 mg/l in the urine. The concentration of 4-MTA in perimortem blood was measured at 4.2 mg/L. This is the first reported case of death involving 4-MTA in the United Kingdom and the first case known to involve 4-MTA only.

Testis biopsy findings in the spinal cord injured patient.

PURPOSE: Azoospermia after electroejaculation in spinal cord injured men may be due to testicular failure or obstruction. These men can initiate pregnancy with assisted reproductive techniques, such as intracytoplasmic sperm injection, but only if sperm are present in the testis biopsy. We analyzed the histopathology of testis biopsies from spinal cord injured men and assessed whether patient factors were predictive of testis biopsy pathology. MATERIALS AND METHODS: A total of 50 paraplegic men undergoing testis biopsy were divided into 2 groups based on normal or abnormal testis histopathology. Patient age, post-injury years, level of lesion, hormonal status and semen analysis results were compared. RESULTS: Spermatogenesis was normal in 28 of the 50 patients. Hypospermatogenesis was exhibited in 15, maturation arrest at the spermatid stage in 6 and maturation arrest at the spermatocyte stage in 1 of the 22 abnormal cases. Nevertheless, mature sperm were identified in 43 of 50 biopsies (normal spermatogenesis and hypospermatogenesis). Men with normal spermatogenesis had better forward progression of sperm and a higher testosterone-to-luteinizing hormone ratio. Otherwise, there was no statistically significant correlation between study variables and testis biopsy results. No factors were predictive of testis biopsy histopathology. CONCLUSIONS: The documentation of mature sperm in 43 of 50 biopsies from spinal cord injured patients suggests that a high rate of sperm retrieval is possible using testicular sperm extraction if sperm cannot be retrieved from the ejaculate. With intracytoplasmic sperm injection techniques the majority of spinal cord injured men retain fertility potential, even if azoospermic following electroejaculation.

Sildenafil citrate after radical retropubic prostatectomy.

PURPOSE: Erectile dysfunction continues to be a significant problem for men after radical retropubic prostatectomy despite nerve sparing techniques. Sildenafil citrate (Viagra) has proved effective for erectile dysfunction in many men. We determine the efficacy of sildenafil in men with erectile dysfunction after radical retropubic prostatectomy and examine variables that may impact the response to treatment. MATERIALS AND METHODS: A total of 84 men were prescribed sildenafil after radical retropubic prostatectomy and asked to complete a series of questionnaires, including the International Index of Erectile Function (IIEF), on erectile function before and after sildenafil administration. The importance of factors, such as patient age, time since surgery, degree of cavernous nerve sparing, preoperative prostate specific antigen, Gleason score, clinical and pathological stage, and baseline postoperative erectile function, was examined. RESULTS: Of the 84 patients 45 (53%) had improved erections and 34 (40%) had improved ability for intercourse while taking sildenafil. Mean IIEF score for the erectile function domain increased from 9 to 14 (p <0.001). Orgasmic function (p = 0.004) and intercourse satisfaction (p = 0.009) also significantly improved. The degree of nerve sparing and baseline postoperative erectile dysfunction had a significant impact on the ability of sildenafil to improve erectile function (p = 0.010 and p <0.001, respectively) and total IIEF questionnaire responses (p = 0.031 and p <0.001, respectively). Age and pathological stage also appeared to have a significant effect. CONCLUSIONS: Sildenafil improved erectile function and the ability to have intercourse in more than half of men after radical retropubic prostatectomy. Baseline postoperative erectile function, which is dependent on the degree of nerve sparing technique, significantly impacts the likelihood that patients will respond to sildenafil.

Characterization of the human Forssman synthetase gene. An evolving association between glycolipid synthesis and host-microbial interactions.

Differences in glycolipid expression between species contribute to the tropism of many infectious pathogens for their hosts. For example, we demonstrate that cultured human and monkey urinary epithelial cells fail to bind a canine Escherichia coli uropathogenic isolate; however, transfection of these cells with the canine Forssman synthetase (FS) cDNA enables abundant adherence by the same pathogen, indicating that addition of a single sugar residue to a glycolipid receptor has marked effects on microbial attachment. Given the contribution of glycolipids to host-microbial interactions, we sought to determine why human tissues do not express Forssman glycolipid. Query of the GenBank(TM) data base yielded a human sequence with high identity to the canine FS cDNA. Reverse transcription polymerase chain reaction and Northern blotting demonstrated the presence of FS mRNA in all tissues examined. A human FS cDNA was characterized, revealing identities with the canine FS gene of 86 and 83% at the nucleotide and predicted amino acid sequences, respectively. In contrast to the canine FS cDNA, transfection of COS-1 cells with the human FS cDNA resulted in no detectable FS enzyme activity. These results suggest that variability in glycolipid synthesis between species is an important determinant of microbial tropism. Evolutionary pressure from pathogenic organisms may have contributed to diversity in glycolipid expression among species.

A previously unidentified acepromazine metabolite in humans: implications for the measurement of acepromazine in blood.

High-performance liquid chromatography-diode-array detection results obtained during the investigation of two cases involving acepromazine prompted us to study the stability of the drug in blood. It was found that acepromazine can undergo in vitro conversion by human red blood cells to 2-(1-hydroxyethyl)promazine, a product that has been reported as a minor urinary metabolite in horse urine but not previously identified in humans. Further, our analytical findings in the two cases examined suggest that 2-(1-hydroxyethyl)promazine may be the major unconjugated metabolite of acepromazine in humans. These findings have important implications for the analytical toxicology of acepromazine.

Analysis of etorphine in postmortem samples by HPLC with UV diode-array detection.

Etorphine is a synthetic narcotic analgesic usually used in veterinary medicine. It possesses an analgesic potency up to 1000 times greater than morphine and is therefore used in low doses, primarily for tranquilising large animals. For veterinary use, etorphine is usually available in its commercial formulation as Immobilon, when in combination with acepromazine or methotrimeprazine. Due to the potency of etorphine, only very low doses are required to produce adverse or fatal effects. This paper describes a method for detecting and quantifying etorphine using HPLC with UV diode array detection (HPLC-DAD) and demonstrates the advantage of the technique for the detection of Immobilon at low doses. In a forensic case involving Immobilon, the etorphine concentrations measured in postmortem femoral vein and heart blood specimens were 14.5 and 23.5 micrograms/l, respectively. No etorphine was detected in the urine. To our knowledge this is the first time postmortem etorphine concentrations have been reported.

Applications of an HPLC-DAD drug-screening system based on retention indices and UV spectra.

An analytical database, using high-performance liquid chromatography (HPLC) with diode array ultraviolet (UV) detection, of over 250 toxicologically relevant drugs has been extensively applied to both clinical and forensic toxicology. This general drug screening system, based on a mixed-phase (octadecyl/cyanopropyl) column and gradient reversed-phase HPLC, can identify a wide range of basic, acidic, and neutral drugs and metabolites, some of which are not amenable to gas chromatography and thin-layer chromatography. Compounds are identified using both retention index (RI) value (calculated by interpolation between a series of reference drug markers) and UV spectral data. It has been previously shown that this chromatographic system provides long-term reproducibility and has potentially useful selectivity differences compared with those based on octadecylsilane columns. Development has been undertaken to improve the speed and practicality of the system for emergency toxicology screening by increasing the rate of the elution gradient, while maintaining the applicability of the RI database. The database has also been found to be an important tool in determining optimum strategies for the adaptation of the system for quantitative analyses of drugs and metabolites under isocratic conditions.