Applying adaptive management and lessons learned from national assessments to address logistical challenges in the National Wetland Condition Assessment.

The National Wetland Condition Assessment (NWCA) is one of a series of probability-based National Aquatic Resource Surveys (NARS) conducted by the U.S. Environmental Protection Agency (USEPA) to provide a comprehensive assessment of the condition of the Nation's waters. Randomized design and standardized training and protocols allow USEPA to analyze data that are nationally consistent and regionally relevant. Each NARS assessment was preceded by careful consideration of key logistical elements that included pre-survey planning, training, sampling logistics, and laboratory analysis. Numerous state, tribal, and contractor crews were supported across the country for each assessment; sampling and sample analyses were tracked from initiation; laboratory analyses were completed at USEPA, state, regional, and contract laboratories; and the data analyses and reporting were completed by USEPA-led workgroups, states, and contractors. The complexity and difficulty of each step offered unique challenges and provided lessons learned for each of the NARS assessments. Major logistical elements for implementing large scale assessments that are constrained by sampling period and number and duration of visits are covered in this paper. These elements include sample transport, equipment and supplies, sampling and sample tracking, information management regional technical expertise, and a sound field training program. This paper describes how lessons from previous assessments were applied to the NWCA and how new challenges faced in the NWCA were addressed and carried forward into future surveys.

A novel fully covered double-bump stent for staple line leaks after bariatric surgery: a retrospective analysis.

BACKGROUND: Staple line leakage after bariatric surgery can be treated by endoscopic placement of a self-expandable stent. The success rate of stent placement is generally high, but migration is a frequent adverse event that hampers successful treatment. The Niti-S Beta stent is a fully covered double-bump stent that was specifically designed to prevent migration. This study aimed to evaluate the effectiveness and adverse event rate of the Niti-S Beta stent. METHODS: A retrospective study was performed in three high-volume bariatric centers. All consecutive patients between 2009 and 2016 who underwent placement of a Beta stent for staple line leakage were included. Primary outcome was resolution of the leakage; secondary outcome was the adverse event rate including migration. RESULTS: Thirty-eight patients were included. Twenty-five (66%) had resolution of the leakage. Success rate was higher in patients who were treated with implantation of a Beta stent as initial treatment (100%) than in patients who were treated with a stent after revisional surgery had failed (55%, p = 0.013). Migration occurred in 12 patients (32%). There were two severe adverse events requiring surgical intervention, including a bleeding from an aorto-esophageal fistula. CONCLUSIONS: The success rate and the migration rate of the Beta stent seem comparable to other stents in this retrospective study. Despite the novel double-bump structure of the stent, the migration rate does not seem to be decreased.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial).

BACKGROUND: The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA. METHODS: A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed. DISCUSSION: The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective. TRIAL REGISTRATION: Netherlands Trial Register (trialregister.nl) 6135 . Date registered: 21-Nov-2016.

Bridging the gap between gastric pouch and jejunum: a bariatric nightmare.

BACKGROUND: Even in a large volume bariatric centre, bariatric surgeons are sometimes confronted with intraoperative anatomical challenges which force even the most experienced surgeon into a pioneering position. In this video we present how a large gap of approximately 8 cm is bridged by applying several techniques that are not part of our standardized surgical procedure. CASE PRESENTATION: After creation of a 20 mL gastric pouch we discovered that the alimentary limb could not be advanced further cranially due to a very short a thick jejunal mesentery in a 49 year old male patient during laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. By dissecting the gastro-oesophageal junction form the crus, stretching the gastric pouch, transecting the jejunal mesentery, using a retrocolic/retrogastric route, and creating a fully hand-sewn gastrojejunostomy we were able to safely complete the LRYGB. Drains were left near the gastrojejunostomy and the patient was kept nil by mouth for 5 days. On the 5th postoperative day radiographic swallow series were obtained which revealed no sign of leakage. The patient was discharged in good clinical condition on the 6th postoperative day. To date, no complications have occurred. Weight loss results are -31.5 % of the preoperative total body weight. CONCLUSIONS: When confronted with a large distance between the gastric pouch and the alimentary limb, several techniques presented in this video may be of aid to the bariatric surgeon. We stress that only experienced bariatric surgeon should embark on these techniques. Inspecting the alimentary limb before the creation of the gastric pouch may prevent the need for such complex techniques.

Interpretation of laboratory results after gastric bypass surgery: the effects of weight loss and time on 30 blood tests in a 5-year follow-up program.

BACKGROUND: Long-term follow-up with blood tests is essential for bariatric surgery to be a successful treatment for obesity and related co-morbidities. Adverse effects, deficiencies, and metabolic improvements need to be controlled. OBJECTIVE: We investigated the effects of time and weight loss on laboratory results in each postoperative phase after laparoscopic Roux-en-Y gastric bypass (LRYGB). SETTING: Bariatric center of excellence, general hospital, Netherlands. METHODS: We retrospectively evaluated results of 30 blood tests, preoperatively and at 6 months, 1 year, 2 years, and 5 years after LRYGB. The 2019 Dutch bariatric chart was used to define weight loss responses as outstanding (>p[percentile curve]+1 SD), average (p+1 SD to p-1 SD), and poor (

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. METHODS: This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. FINDINGS: Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. INTERPRETATION: Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. FUNDING: The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.

Risk Factors for Cholecystectomy After Laparoscopic Roux-En-Y Gastric Bypass.

BACKGROUND: Patients who have undergone bariatric surgery are at risk for subsequent cholecystectomy. We aimed to identify risk factors for cholecystectomy after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: We conducted a retrospective case-control study of patients who underwent LRYGB between 2013 and 2015. Cases underwent cholecystectomy because of biliary symptoms after LRYGB. For each case, two controls were selected without subsequent cholecystectomy. Logistic regression analyses were used to identify risk factors. RESULTS: Between 2013 and 2015, 1780 primary LRYGBs were performed. We identified 233 (13.1%) cases who had undergone cholecystectomy after a median (IQR) of 12 (8-17) months, and 466 controls. Female gender (OR (95% CI) 1.83 (1.06-3.17)), Caucasian ethnicity (OR (95% CI) 1.82 (1.10-3.02)), higher percent total weight loss (%TWL) at 12 months (OR (95% CI) 1.06 (1.04-1.09)), and preoperative pain syndrome (OR (95% CI) 2.72 (1.43-5.18)) were significantly associated with an increased risk for cholecystectomy. Older age (OR (95% CI) 0.98 (0.96-0.99)) and preoperative statin use were associated with a reduced risk (OR (95% CI) 0.56 (0.31-1.00)). A dose-effect relationship was found between the intensity of preoperative statin and risk for cholecystectomy. CONCLUSIONS: In our study, higher %TWL and preoperative pain syndrome were associated with an increased risk for cholecystectomy besides the traditional risk factors female gender and Caucasian ethnicity. These factors can be used to identify high-risk patients, who might benefit from preventive measures. Whether statins can protect bariatric patients from developing gallstones should be investigated prospectively.

Gastrointestinal symptoms before and after laparoscopic Roux-en-Y gastric bypass: a longitudinal assessment.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective treatment for morbid obesity, but many patients have increased gastrointestinal symptoms. OBJECTIVES: To evaluate gastrointestinal symptoms and food intolerance before and after RYGB over time in a large cohort of morbidly obese patients. SETTING: A high-volume bariatric center of excellence. METHODS: A prospective cohort study was performed in patients who underwent RYGB between September 2014 and July 2015, with 2-year follow-up. Consecutive patients screened for bariatric surgery answered the Gastrointestinal Symptom Rating Scale (GSRS) and a food intolerance questionnaire before RYGB and 2 years after surgery. The prevalence of gastrointestinal symptoms before and after surgery and the association between patient characteristics and postoperative gastrointestinal symptoms were assessed. RESULTS: Follow-up was 86.2% (n = 168) for patients undergoing primary RYGB and 93.3% (n = 28) for revisional RYGB. The total mean GSRS score increased from 1.69 to 2.31 after surgery (P < .001), as did 13 of 16 of the individual scores. Preoperative GSRS score is associated with postoperative symptom severity (B = .343, P < .001). Food intolerance was present in 16.1% of patients before primary RYGB, increasing to 69.6% after surgery (P < .001). Patients who underwent revisional RYGB had a symptom severity and prevalence of food intolerance comparable with that among patients with primary RYGB, even though they had more symptoms before revisional surgery. CONCLUSIONS: Two years after surgery, patients who underwent primary RYGB have increased gastrointestinal symptoms and food intolerance compared with the preoperative state. It is important that clinicians are aware of this and inform patients before surgery.

Dietary-induced variation of hypoxanthine-guanine phosphoribosyl transferase activity in patients with the Lesch-Nyhan syndrome.

We have studied three patients with the Lesch-Nyhan syndrome to assess the effect of dietary purines on erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity. During dietary purine restriction HGPRT activity rose in all three patients; resumption of normal dietary purine intake or the addition of adenine (10 mg/kg per day) to a purinefree diet resulted in a fall in HGPRT activity. These changes in enzyme activity appeared to be due to an activation or inactivation of the mutant enzyme without a change in the half-life or absolute amount of HGPRT enzyme protein.

Hypoxanthine-guanine phosphoribosyltransferase: characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome.

The Lesch-Nyhan syndrome is characterized clinically by choreoathetosis, spasticity, selfmutilation, and mental and growth retardation. Biochemically, there is a striking reduction of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity in affected individuals. We have examined erythrocytes from 14 patients with the Lesch-Nyhan syndrome for the presence of hypoxanthine-guanine phosphoribosyltransferase activity and enzyme protein. In contrast to the usual finding of no detectable hypoxanthine-guanine phosphoribosyltransferase activity, we have found low levels (0.002-0.79 nmoles/mg protein per hr) of hypoxanthine-guanine phosphoribosyltransferase activity in erythrocyte lysates from five of these patients. In three of the five patients, hypoxanthine-guanine phosphoribosyltransferase activity appeared to be substantially more labile in vivo than normal using erythrocytes which had been separated according to their density (age). Immunochemical studies using a monospecific antiserum prepared from a homogeneous preparation of normal human erythrocyte hypoxanthine-guanine phosphoribosyltransferase revealed immunoreactive protein (CRM) in hemolysate from all 14 patients with the Lesch-Nyhan syndrome. The immunoreactive protein from each patient gave a reaction of complete identity with normal erythrocyte hypoxanthine-guanine phosphoribosyltransferase and was present in quantities equal to those observed in normal erythrocytes. In addition, a constant amount of CRM was found in erythrocytes of increasing density (age) from patients with the Lesch-Nyhan syndrome despite the decreasing hypoxanthine-guanine phosphoribosyltransferase activity. These studies confirm previous data which indicate that the mutations leading to the Lesch-Nyhan syndrome are usually, if not always on the structural gene coding for hypoxanthine-guanine phosphoribosyltransferase. In addition, although the mutant proteins appear to be present in normal amounts, they are often very labile in vivo with respect to enzymatic activity. These observations suggest that therapy directed at stabilization or activation of enzyme activity in vivo may be of potential benefit.

Internal Herniation After Laparoscopic Roux-en-Y Gastric Bypass Surgery: Pitfalls in Diagnosing and the Introduction of the AMSTERDAM Classification.

INTRODUCTION: Internal herniation (IH) probably is the most elusive complication of laparoscopic Roux- en-Y gastric bypass (LRYGB) surgery. This study provides a definition for IH, a diagnosing algorithm, and information on several factors influencing IH formation. METHOD: Baseline characteristics, laboratory findings, imaging studies, operative findings, and follow up data of 1583 patients that underwent LRYGB at our bariatric facility between 2007 and 2013 were recorded. Follow up varied between 3 and 76 months, and 85 % of the data was available for analysis at 12 months. Our surgical technique was standardized. Intermesenteric spaces were not closed until July 2012, where after they were closed. To facilitate comparison, IH cases were matched with controls. RESULTS: Forty patients (2.5 %) had an IH during re-laparoscopy. The modal clinical presentation is acute onset epigastric discomfort, often crampy/colicky in nature. Additional examinations included laboratory testing, abdominal X-ray, abdominal ultrasound, and abdominal CT scanning. Patients who developed an IH lost a significantly higher percentage of their total body weight than their matched controls at every time point. IH incidence was higher in the non-closure group than the closure group. CONCLUSION: The large variation in reported IH incidence is due to the large variation in IH definition. To gain more uniformity in reporting IH prevalence, we propose the use of the AMSTERDAM classification. Post-LRYGB patients with acute onset crampy/colicky epigastric pain should undergo abdominal ultrasound to rule out gallbladder pathology and offered re-laparoscopy with a low threshold. IH incidence is highest among patients with rapid weight loss and non-closure of intermesenteric defects.

Risk Stratification Models: How Well do They Predict Adverse Outcomes in a Large Dutch Bariatric Cohort?

BACKGROUND: Risk prediction models are useful tools for informing patients undergoing bariatric surgery about their risk for complications and correcting outcome reports. The aim of this study is to externally validate risk models assessing complications after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. METHODS: All 740 patients who underwent a primary LRYGB between December 2007 and July 2012 were included in the validation cohort. PubMed was systematically searched for risk prediction models. Eight risk models were selected for validation. We classified our complications according to the Clavien-Dindo classification. Predefined criteria of a good model were a non-significant Hosmer and Lemeshow test, Nagelkerke R (2) ≥ 0.10, and c-statistic ≥0.7. RESULTS: There were 85 (7.8 %) grade 1, 54 (7.3 %) grade 2, 5 (0.7 %) grade 3a, 14 (1.9 %) grade 3b, and 14 (1.9 %) grade 4a complications in our validation cohort. Only one model predicted adverse events satisfactorily. This model consisted of one patient-related factor (age) and four surgeon- or center related factors (conversion to open surgery, intraoperative events, the need for additional procedures during LRYGB and the learning curve of the center). CONCLUSIONS: The overall majority of the included risk models are unsuitable for risk prediction. Only one model with an emphasis on surgeon- and center-related factors instead of patient-related factors predicted adverse outcome correctly in our external validation cohort. These findings support the establishment of specialty centers and warn benchmark data institutions not to correct bariatric outcome data by any other patient-related factor than age.

Fixed-dose enoxaparin after bariatric surgery: the influence of body weight on peak anti-Xa levels.

INTRODUCTION: There is lack of data on the pharmacodynamics of low-molecular-weight heparins in obese patients. BACKGROUND: The aims of this study are to investigate the correlation between anti-factor Xa (anti-Xa) levels and body weight with fixed-dose enoxaparin after bariatric surgery and to investigate the percentage of patients that reach the desired prophylactic range for anti-Xa levels. METHODS: Blood for anti-Xa peak levels measurement was drawn 3-5 h after administration of enoxaparin at the planned visit 8-16 days after surgery. Patients were included in three categories: <110 kg (group 1), 110-150 kg (group 2), and >150 kg (group 3). RESULTS: Fifty-one patients were included (43.9 ± 9.9 years, 75% women). Mean anti-Xa level was 0.37 ± 0.14 IU/ml. This level was the highest in group 1 (0.47 ± 0.13 IU/ml) and lowest in group 3 (0.23 ± 0.07). No subprophylactic (<0.2 IU/ml) anti-Xa levels were detected in group 1, whereas this was observed in 38% in patients in group 3. Supraprophylactic levels (>0.5 IU/ml) were most often present in group 1 (36%). With multivariable regression analysis, body weight (ß -0.720 (95 % confidence interval -.717; -.993), p < 0.001) was an independent predictor of anti-Xa levels, whereas lean body was not independently associated. This was confirmed in a non-linear mixed effects analysis of the data. CONCLUSIONS: Patients with excessive body weight may not be adequately treated with fixed-dose enoxaparin thromboprophylaxis while patients with lower body weight may have an increased bleeding risk. Body weight is a better predictor of anti-Xa levels compared to lean body weight.

The Preceding Surgeon Factor in Bariatric Surgery: a Positive Influence on the Learning Curve of Subsequent Surgeons.

BACKGROUND: The learning curve of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery has been well investigated. The learning curve is defined by complications and/or by duration of surgery (DOS). Previous studies report an inverse relationship between patient outcome and patient volume. In this study, we investigate whether the learning curve of preceding bariatric surgeons is of additional influence for surgeons who start to perform LRYGB in the same centre. MATERIALS AND METHODS: We retrospectively analysed the records of all 713 consecutive primary LRYGB patients operated in our centre from December 2007 until July 2012. Surgeon 1 and 3 had previous laparoscopic bariatric experience whilst Surgeon 2 and 4 had not. We stratified the data between the four surgeons with different levels of experience and in a chronology of 50 cases. RESULTS: Sixty-seven (9.4 %) complications occurred in the study period. Surgeon 1 had more complications occurring within the first 50 cases than Surgeon 4 (10 versus 1, p < 0.05). There was no difference in complication rate between groups of 50 consecutive cases. None of the patients died. DOS decreased for every consecutive surgeon, irrespective of their experience. The learning curve defined by DOS was steepest for Surgeon 1, followed by Surgeon 2, 3 and 4. CONCLUSION: In this study, we show that the learning curve of the preceding surgeon positively influences the learning curve of latter surgeons, irrespective of their experience. Therefore, the 'preceding surgeon factor' should be taken in account in addition to volume requirements when starting new bariatric facilities.

Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency.

Immunologic and metabolic abnormalities were studied in a five year old boy with 0.07 per cent of normal erythrocyte purine nucleoside phosphorylase activity. The clinical course is characterized by severe autoimmune hemolytic anemia, a transient neurologic disorder with tremor and ataxia, and minor infectious illnesses. There is severe lymphopenia with decreased absolute numbers of T and B lymphocytes. Mitogen-stimulated blastogenesis is reduced, but response to allogeneic lymphocytes is normal. A monoclonal IgG protein is present. There is hypouricemia, elevated plasma inosine level, hypouricosuria and an increase in the urinary concentration of inosine and guanosine. The pattern of heterozygote distribution in the patient's family is compatible with an autosomal recessive trait in which heterozygotes are identifiable. In addition, the unusual laboratory and clinical manifestations of this patient illustrate the heterogeneity of the clinical syndrome associated with purine nucleoside phosphorylase deficiency.

A short-term study of nitrofurantoin prophylaxis in children managed with clean intermittent catheterization.

OBJECTIVE: Because there is no evidence for the effectiveness of antibiotic prophylaxis in children with neurogenic bladder, the value of once-daily nitrofurantoin macrocrystals was assessed in a selected population with neurogenic bladder due to meningomyelocele. METHODS AND TRIAL POPULATION: Children with significant urinary tract abnormalities other than neurogenic bladder were excluded. A urinary tract "infection" was defined as > or = 10(8) colony forming units of bacteria/L of urine together with pyuria of > or = 50 x 10(6) leukocytes/L, and/or symptoms consistent with an urinary tract infection. Fifty-six children participated in a 24-week double-blinded, placebo-controlled cross-over study. The infection status was assessed at two weekly intervals or if relevant clinical manifestations occurred. RESULTS: For the whole trial the average percentage of "infections" per urine sample for each patient was reduced from 39% on placebo to 19% on single daily dose prophylaxis (P < .0003). For the first 12 weeks of the trial corresponding figures were 45% on placebo and 22% on prophylaxis (P < .0018). There was evidence for a marked carryover protective effect of nitrofurantoin into the placebo arm of the trial. CONCLUSION: Nitrofurantoin is an effective prophylactic agent during a 3-month period. Long-term studies are needed to confirm the reasonable expectation of a beneficial effect on urinary tract damage.

Laboratory variables of bladder autoaugmentation in an animal model.

OBJECTIVES: Evaluations of the functional, radiologic, and pathologic outcomes of autoaugmentation by two surgical techniques (vesicomyectomy versus vesicomyotomy) were compared. Autoaugmentation or vesicomyotomy is being increasingly considered as a simplified method of bladder augmentation in the hypertonic decreased-capacity bladder. METHODS: In a series of 35 laboratory sessions, creation of an animal model approximating the small-capacity hypertonic bladder was achieved. Sixteen vesicomyotomies and 16 vesicomyectomies were performed on the 32 stabilized one-third reduced bladders. Three stabilized one-third reduced bladders were used as controls. RESULTS: Radiologic studies show a large diverticulum. A 17.2% net increase in surface area was achieved, compared with the reduced bladder, at the time of pathologic examination. Functional capacity was increased by 43.5% on urodynamic studies, and leak point pressure was decreased by 48.1%. Histologic and morphometric examinations of the autoaugmentation area showed a few muscle fibers with serosal deposition of collagen. There was less muscle ingrowth at the periphery of the autoaugmentation site utilizing vesicomyectomy. CONCLUSIONS: There was no statistical difference between vesicomyotomy and vesicomyectomy with respect to radiologic, pathologic, or urodynamic outcome.

Prerandomization: an alternative to classic randomization. The effects on recruitment in a controlled trial of arthroscopy for osteoarthrosis of the knee.

Possibly the greatest threat to the success of a randomized clinical trial is the inability to recruit an adequate number of subjects. Concern that the randomized clinical trial will adversely affect the physician-patient relationship is the most common reason for physicians' reluctance to enroll patients in such trials. We report a modification of a prerandomized design, first described by Zelen, which was implemented in a randomized clinical trial of arthroscopy for patients who had osteoarthrosis of the knee. The method was associated with a sixfold increase in the rate of accrual of patients as compared with the use of a classic randomization trial. We propose the design as a potential solution to the problem of recruitment of subjects, particularly for clinical studies.

Role of perilymph in the early stage of serous otitis.

After injection of an electron-dense tracer into the cerebrospinal fluid (CSF) the particles can be seen within the lymphatic spaces of the middle ear mucosa after a few minutes. They find their way via the well known communication routes from CSF to the perilymphatic spaces of the inner ear. From there they enter through open fluid spaces into the fibrocytic network of the round window membrane which stands in open relationship to the extracellular fluid spaces of the middle ear mucosa. They were drained to the regional lymph nodes by lymphatic vessels. When inducing a serous otitis by experimental obstruction of the Eustachian tube it could be demonstrated that the fluid within the middle ear cavity is partly coming from the CSF and perilymph. Later the healing process of the middle ear epithelium was studied after the onset of serous otitis with and without artificial ventilation of the middle ear.

Squamous cell carcinoma of the vulva and Fanconi anemia.

Malignant neoplasia frequently occurs with Fanconi anemia. Generally this represents hematologic disease; however, solid tumors may also appear. The woman described here developed squamous cell carcinoma of the vulva at age 28, and is the third such case in a patient with Fanconi anemia that has been reported. It is a diagnosis to be considered for the young patient with this type of carcinoma. Increased chromosomal breakage in this syndrome may be important in the pathogenesis of these neoplastic changes.