Revealing the spatiotemporal patterns of bacterial infectious diseases using bioluminescent pathogens and whole body imaging.
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Animals↗
Biomedical subjects
L D Shortliffe
Publications and source records attributed to L D Shortliffe.
Magnetic resonance imaging for the evaluation of hydronephrosis, reflux and renal scarring in children.
PURPOSE: We studied the effectiveness of magnetic resonance imaging (MRI) for evaluating hydronephrosis, differential renal function, vesicoureteral reflux and renal scarring in children. MATERIALS AND METHODS: A total of 16 patients with hydronephrosis were evaluated with MRI. Coronal T1 and axial T1 and T2-weighted images were obtained before and after the administration of intravenous contrast material. Patients with vesicoureteral reflux underwent magnetic resonance voiding cystourethrography. Differential renal function was estimated from differential parenchymal volumes determined from MRI using computer software. The results were compared to standard imaging modalities. RESULTS: A total of 19 MRI studies were performed in 16 patients, including 3 for ureteropelvic junction obstruction, 11 for vesicoureteral reflux and 2 for other conditions. MRI provided the best anatomic detail and clear corticomedullary differentiation. MRI identified renal scarring and cortical thinning in 8 cases, while mercaptoacetyltriglycine 3 scans did not show any renal scarring and single photon emission computerized tomography-dimercapto-succinic acid nuclear scans diagnosed only 4 of 5 cases. There was good correlation between differential function obtained from nuclear scans and differential parenchymal volumes obtained from MRI (correlation coefficient 0.86, r2 = 0.74). Magnetic resonance voiding cystourethrography diagnosed reflux in 4 of 5 patients in whom vesicoureteral reflux was previously documented by standard voiding cystourethrography. CONCLUSIONS: MRI provides an alternative for the evaluation of hydronephrosis in children by combining the information provided by functional and anatomic nuclear scans, voiding cystourethrography and ultrasonography in a single study without ionizing radiation. MRI appears to be as good as existing modalities in the evaluation of renal scarring and cortical thinning.
Adolescent↗
Laparoscopy for the evaluation and management of the nonpalpable testicle.
OBJECTIVE: To assess the usefulness of laparoscopy for the diagnosis and treatment of the nonpalpable testicle and to evaluate the results of laparoscopic orchidopexy. METHODS: We retrospectively reviewed the charts of 91 laparoscopies performed over a period of 4 years. We reviewed the following parameters: findings, complications, patency of the processus vaginalis, appearance of the cord structures, and the success of the different procedures performed for the intra-abdominal testicle. RESULTS: Fourteen patients had bilateral and 77 unilateral nonpalpable testicles. The mean age of the patients was 39.5 +/- 50.8 months. There were three laparoscopic complications (3.2%) one of which was a major bowel laceration. Laparoscopy defined the intra-abdominal anatomy accurately in 90 of the 91 cases Of the 26 intra-abdominal testicles above the ring, a one-stage laparoscopic orchidopexy was performed in five and a single-stage standard orchidopexy in seven. All of these testicles remain viable and are in good position. Eight patients underwent a staged Fowler-Stephens orchidopexy with laparoscopic clipping of the spermatic vessels as the first stage. Of these, a second-stage open orchidopexy was performed in five and a laparoscopic orchidopexy in three. Testicular atrophy occurred in two of the patients who underwent the second-stage open orchidopexy. Three one-stage Fowler-Stephens orchidopexies were performed with testicular atrophy occurring in two of these testicles. Laparoscopic orchiectomy was performed on two patients. CONCLUSIONS: Laparoscopy is a valuable tool in the diagnosis and treatment of the nonpalpable testicle. Laparoscopic orchidopexy may decrease the rate of testicular atrophy since most of these can be performed laparoscopically in one stage, thus preserving the vascular supply.
Adolescent↗
The urodynamic relationship of renal pelvic and bladder pressures, and urinary flow rate in rats with congenital vesicoureteral reflux.
PURPOSE: We define the relationship of renal pelvic and bladder pressures with varying urinary flow rates and bladder fullness in unobstructed rats with and without vesicoureteral reflux. MATERIALS AND METHODS: Sprague-Dawley rats (180 to 250 gm.) were evaluated for vesicoureteral reflux followed by simultaneous and continuous renal pelvic and bladder pressure monitoring during bladder filling cycles. RESULTS: The incidence of congenital right vesicoureteral reflux was 25% (14 of 57 rats, below bladder pressure of 40 cm. water). The renal pelvic pressure was significantly higher in rats with reflux compared to normal rats only at very low urine output when the bladder was 90% full or greater and when the urine output was moderate with the bladder 50% full or less. For all other urine outputs and degrees of bladder fullness, there were no significant differences in pelvic pressure between rats with and without reflux. CONCLUSIONS: Renal pelvic pressures in the refluxing and nonrefluxing collecting system of rats with mild to moderate reflux do not differ except under well-defined conditions. Reflux can be induced by raising the intravesical pressure when the urinary flow rate is very low. Furthermore, vesicoureteral reflux pressures decrease post mortem. Therefore, the observation of vesicoureteral reflux is a relative phenomenon defined by urinary flow rate, bladder pressure and in vivo conditions, and one must define the specific bladder pressure and urinary flow rate that are present when reflux occurs. These data help explain why the observation of reflux may be intermittent or transient during various imaging studies.
Animals↗
The use of renal parenchymal area in children with high grade vesicoureteral reflux.
PURPOSE: We sought to apply 2-dimensional sonographic measurements of renal parenchymal area in children with high grade vesicoureteral reflux to assess reliability and accuracy in estimating differential renal function, and in predicting clinical outcome compared to traditional 1-dimensional sonographic measurements. MATERIALS AND METHODS: We retrospectively evaluated 121 sonograms from 30 patients with a grade 4 or 5 primary vesicoureteral reflux, including 14 who underwent ureteral reimplantation during followup and 16 who were followed on prophylactic antibiotic therapy. One-dimensional sonographic measurements of longitudinal length and bipolar thickness were determined in refluxing and contralateral kidneys, as were 2-dimensional measurements of longitudinal parenchymal area using computer planimetry. Renal length, bipolar thickness and parenchymal area were compared to renal function data determined by nuclear renography. Renal length and area was also represented as a percent of age adjusted normal values using previously published nomograms. RESULTS: Differential renal function correlated well with differential parenchymal area for all patients (r = 0.924). This correlation persisted in patients with (r = 0.917) and without scarring (r = 0.890), as determined by dimercapto-succinic acid scan. Differential length did not correlate as well (r = 0.661) and bipolar parenchymal thickness did not correlate at all (r = 0.021). Sonographic age adjusted area of the refluxing kidneys was approximately two-third normal. No statistically significant difference was observed among age adjusted renal area of the observation, preoperative and postoperative groups. Contralateral kidney area was not significantly different than normal. CONCLUSIONS: Our data indicate that serial sonographic measurements of longitudinal renal parenchymal area provide a simple and accurate method of monitoring renal growth and function in patients with high grade vesicoureteral reflux. In contrast to 1-dimensional measurements of renal length and bipolar parenchymal thickness, renal parenchymal area correlates well with renal function. Area also appears to be a more sensitive method of monitoring renal growth in children with vesicoureteral reflux.
Child, Preschool↗
Normal pediatric testis: comparison of power Doppler and color Doppler US in the detection of blood flow.
PURPOSE: To compare power Doppler and conventional color Doppler ultrasound (US) in the detection of blood flow in the normal pediatric testis and to assess the symmetry of blood flow and the spectral Doppler tracing waveforms in the normal pediatric testis. MATERIALS AND METHODS: Testicular blood flow was assessed prospectively in 68 testes in 34 boys (age range, 6 weeks to 13 years; mean age, 4.6 years) with both conventional color and power Doppler US. Intratesticular blood flow was graded as follows: 0, no intratesticular flow; 1, single intratesticular Doppler signal identified; and 2, multiple intratesticular Doppler signals identified. The symmetry of intratesticular flow was assessed both subjectively and objectively by using the same grading system. Spectral Doppler tracings were obtained in 62 testes in 31 patients. RESULTS: Power Doppler US demonstrated intratesticular blood flow in 66 (97%) testes. Color Doppler US demonstrated intratesticular blood flow in 60 (88%) testes. Combined techniques depicted blood flow in all 68 (100%) testes. Testicular blood flow was judged symmetric in all 34 (100%) patients with power Doppler US and in 31 (91%) patients with color Doppler US. Spectral Doppler tracings demonstrated absence of diastolic flow in 20 (32%) of 62 testes. CONCLUSION: In children, power Doppler US is more sensitive than color Doppler US in the detection of intratesticular blood flow. With power Doppler US, testicular blood flow in healthy children is symmetric, underscoring that the asymptomatic testis can be used as a baseline for assessing flow in the symptomatic testis.
Child, Preschool↗
Outcome analysis of the modified Mathieu hypospadias repair: comparison of stented and unstented repairs.
PURPOSE: We compared surgical outcomes of stented and unstented Mathieu repairs in boys with primary distal hypospadias, and evaluated the efficacy and safety of caudal analgesia relative to other forms of analgesia (penile block and epidural analgesia). MATERIALS AND METHODS: We retrospectively reviewed the records of 336 consecutive boys who underwent the modified Mathieu repair for primary distal hypospadias. A urethral stent was placed in 114 patients and nonstented repair was performed in 222. Adjunct caudal analgesia was given in 136 cases, a penile block in 158 and continuous epidural analgesia in 42. RESULTS: None of the unstented cases had urinary retention. Analysis of surgical outcomes revealed no difference in fistula formation between patients with and without stents (2.63 versus 2.70%, respectively, p > 0.999). Overall complication rates in the stented and unstented groups were not significantly different (2.63 versus 3.60%, respectively, p = 0.756). The fistula rate in patients who received adjunct caudal analgesia was no different than in those who received other forms of adjunct analgesia (2.21 versus 3.0%, respectively, p > 0.999). CONCLUSIONS: These data suggest that successful Mathieu hypospadias repair is independent of the use of a stent. Caudal analgesia, a penile block and epidural analgesia provided effective postoperative pain control with no difference in complication rates. To our knowledge our report represents the largest observational study reported to date comparing stented and unstented repairs. However, because of the small number of complications in each group, a much larger study is required to determine statistically significant differences among these groups.
Adolescent↗
The histology of interstitial cystitis.
Several studies have reported histologic findings in interstitial cystitis (IC) bladder biopsy specimens. However, these studies used a variety of criteria to define IC, which may explain the variation noted in the histologic changes. Clinical experience shows that these biopsy specimens are often not helpful in confirming the diagnosis. Our study was designed to examine the histologic features identified in bladder biopsy specimens from patients with IC and compare them with biopsy specimens from a control population. Although IC patients as a group had a higher incidence and degree of denuded epithelium, ulceration, and submucosal inflammation, none of these findings was pathognomonic. In addition, these findings occurred only in interstitial cystitis patients with pyuria or small bladder capacity. The inflammatory infiltrate seen in IC was composed predominantly of lymphocytes, with increasing numbers of plasma cells as the degree of inflammation increased. There was no specific predilection for the inflammatory infiltrate to be perineural. Submucosal inflammation was associated with denuded epithelium, ulceration, pyuria, and a clinical response to therapy suggesting a pathophysiologic relationship. Epithelial and basement membrane thickness, submucosal edema, vascular ectasia, fibrosis, and detrusor muscle inflammation and fibrosis were not significantly different in the IC and control patients. These findings suggest that IC is a chronic submucosal inflammatory disease, at least in those patients with small bladder capacities or pyuria. IC is best diagnosed from its clinical features; the histologic changes identified in the bladder biopsy play a supportive role in this diagnosis. Mast cells play a limited role in the diagnosis of IC.
Biopsy↗
Alpha-interferon in superficial bladder cancer: a Northern California Oncology Group Study.
Thirty-five patients with superficial transitional carcinoma of the bladder were treated intravesically with escalating doses of recombinant alpha-2-interferon administered weekly for 8 weeks. Of the 19 patients with high-grade intraepithelial neoplasia (17 carcinoma in situ [CIS], two severe dysplasia, all cytology positive), six (32%) had complete resolution of all histologic and cytologic evidence of disease (complete response). An additional three patients (16%) had complete resolution of CIS, but the interval appearance of a low-grade transitional cell neoplasm. Five (26%) had a partial response (complete resolution of all evidence of CIS on multiple bladder biopsies but persistently positive cytologic preparations). Sixteen patients with recurrent papillary tumors and extensive prior therapy were also treated. Four (25%) had a complete response. Twenty-three of the 35 patients had prior intravesical therapy. Seven of the 23 (30%) patients with prior intravesical chemotherapy or immunotherapy had a complete or partial response to interferon, while eight of the 12 patients (67%) without prior intravesical treatment responded. These responses were achieved with minimal local and systemic toxicity. Of the ten complete responders, five remain in continuous unmaintained remission for 18+ to 37+ months. Intracavitary alpha-2-interferon is an effective new treatment for some patients with bladder cancer.
Adult↗
Mast cell involvement in interstitial cystitis.
A prospective study was designed to examine the relationship of mast cells, and eosinophilic leukocyte density and mediator levels to clinical and histological parameters of interstitial cystitis. Interstitial cystitis and control patients underwent bladder biopsy with histological examination, and quantification of intact and degranulated mast cell and eosinophilic leukocyte density. In addition, bladder tissue histamine content, urinary prostaglandin E2 excretion rates, and serum and urinary major basic protein levels were determined. A strong relationship among detrusor mast cell density, especially degranulated, and degree of epithelial loss, submucosal inflammation, epithelial ulceration, urinary pyuria and response to treatment was noted. Bladder tissue histamine content and urinary prostaglandin E2 excretion were increased in the interstitial cystitis patients. Eosinophil density in bladder biopsies was low uniformly, and interstitial cystitis and control patients showed no statistical difference. In addition, serum and urinary major basic protein levels were below the accepted normal lower limits for this protein. Therefore, our study demonstrates a relationship between the mast cell and the inflammatory process of interstitial cystitis. No similar relationship was noted for the eosinophil.
Biopsy↗
Superficial bladder cancer: the primacy of grade in the development of invasive disease.
Tumor characteristics thought to predict for development of deep muscle invasion after resection of superficial bladder cancer were retrospectively analyzed in 252 patients with transitional cell carcinoma of the bladder at Stanford University Medical Center. Stage 0 patients accounted for 190 of the patient population (75.5%), while stage A and B1 comprised 51 (20%) and 11 (4.5%), respectively. The median follow-up time was 62 months. Forty-three patients subsequently developed deep muscle invasion; these included 24 (12.6%), 14 (27.5%), and 5 (45.5%) of stage 0, A, and B1 patients (P = .002), or 15 (10%), 15 (9%), and 13 (33%) of grade 1, 2, and 3 tumors (P = .001), respectively. When analyzed by univariate logistic regression, grade (P = .0001) and stage (P = .0118) were significant predictors for invasive disease. Site of tumor and number of tumors at presentation were not significant factors for invasion deep into the bladder wall. When multiple logistic regression was performed, only grade remained as a significant tumor variable to predict for invasive disease (P less than .0091). Risk of invasive disease did not appear to increase with increasing number of recurrences, remaining at approximately an 11% invasion rate through 12 recurrences. In this analysis, grade was the most significant tumor variable in superficial bladder cancer predicting for the development of invasive carcinoma. Future clinical trials for definitive or adjuvant therapy of this disease must stratify for this variable.
Adult↗
A randomized study of doxorubicin versus doxorubicin plus cisplatin in endocrine-unresponsive metastatic prostatic carcinoma.
Thirty-seven patients with hormonally refractory prostatic carcinoma entered a randomized trial comparing doxorubicin and doxorubicin plus cisplatin. All patients had failed prior hormonal treatment. Mean Karnofsky performance status (76% doxorubicin versus 75% combination), percent of patients with prior palliative irradiation (40% doxorubicin versus 35% combination), and hemoglobin levels of less than or equal to 12 g/dl (30% doxorubicin versus 24% combination) were roughly equivalent in the two treatment groups. More patients treated with doxorubicin than the combination treatment had an elevated acid phosphatase level at study entry (90% versus 65%). Measurable bidimensional tumors were present in 13 patients in 16 sites in the doxorubicin arm and in 10 patients in 11 sites in the combination arm. Partial responses were seen in 1 of 13 patients in the doxorubicin arm and 2 (20%) of 10 patients in the combination arm. Improvement in Karnofsky performance status of 20% or greater was rarely observed with either treatment (7% doxorubicin versus 8% combination). Acid phosphatase levels normalized or improved by 50% in 39% of patients who received doxorubicin and 27% of patients who received the combination. The overall response rate by National Prostatic Cancer Project Criteria was 53% for doxorubicin and 59% for doxorubicin plus cisplatin. Myelotoxicity and gastrointestinal toxicity were severe, particularly in the combination arm, and required discontinuation of treatment in some patients who responded to treatment. Moderate renal dysfunction (creatinine value 2.0-3.0 mg/dl) occurred only in the combination arm at an incidence of 23%. Time to progression and survival were similar for the two treatment groups. In this small group of 37 patients, the combination of cisplatin and doxorubicin showed no improvement over doxorubicin alone in response, response duration, or survival, and was difficult to administer in this patient population.
Adenocarcinoma↗
The fate of the bladder in patients with metastatic bladder cancer treated with cisplatin, methotrexate and vinblastine: a Northern California Oncology Group study.
We report the efficacy and toxicity of combined cisplatin, methotrexate and vinblastine for the treatment of metastatic transitional cell carcinoma of the bladder in 50 evaluable patients. Of these 50 patients 17 had not undergone cystectomy and had residual invasive bladder cancer. Of these 17 patients 11 had complete response of the bladder lesions following cisplatin, methotrexate and vinblastine for metastatic disease, including 6 of 12 treated by cisplatin, methotrexate and vinblastine alone, and 5 of 5 treated with cisplatin, methotrexate and vinblastine plus palliative or preoperative pelvic irradiation. Complete response was confirmed in 10 of the 11 patients by endoscopy and biopsy, and in 1 by cystectomy. One patient whose liver metastasis responded to cisplatin, methotrexate and vinblastine had conversion to complete response by cystectomy for persistent bladder cancer. Of these 17 patients 7 are alive, including 5 without disease, 4 to 41 months after treatment. The bladder appears to be responsive to this combination chemotherapy for invasive transitional cell carcinoma. This experience underscores the need for regular pathological re-staging of the bladder cancer in patients receiving chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
Cisplatin, methotrexate, and vinblastine (CMV): an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study.
Fifty-eight patients with metastatic transitional cell carcinoma of the urinary tract received cisplatin, methotrexate, and vinblastine (CMV) combination chemotherapy. Complete responses (CRs) were noted in 14 of the 50 (28%) evaluable patients and partial responses (PRs) in 14 patients for an overall response rate of 56% (95% confidence limits of 42% to 70%). The median duration of the 14 CRs was 9 months. Six of the 14 CRs (43%) remain in unmaintained remission from 6 + to 35 + months from onset of treatment. The median survival of evaluable patients receiving CMV was 8 months. Median survival for CRs was 11 months v 7 months for PRs (P less than .05) and 6 months for nonresponders. Renal and hematologic toxicities with this regimen were moderate. CMV is an effective regimen for patients with metastatic transitional cell carcinoma of the bladder. Prolonged disease-free survival may result from a CR to this regimen.
Actuarial Analysis↗
The extent of surgery after chemotherapy for advanced germ cell tumors.
The histopathological findings of tissue removed from 40 patients with a residual mass after completion of induction chemotherapy with cis-platinum, vinblastine and bleomycin are reviewed. These patients with advanced testicular cancer were treated with chemotherapy until normalization of tumor markers and until there was no further decrease in the size of palpable or radiologically evident masses for 2 successive cycles of chemotherapy. The mean number of chemotherapy cycles preoperatively was 5.2. Residual carcinoma was found in only 1 patient (3 per cent), teratoma in 18 (45 per cent), and fibrotic and/or necrotic masses in 21 (52 per cent). With this tailored treatment regimen in which an operation is performed after maximal chemotherapeutic response, the number of patients with viable residual tumor at operation can be minimized. Complete retroperitoneal lymph node dissection concomitant with resection of the residual mass was performed in 22 of 32 patients with residual masses in the retroperitoneum. The 1 patient with carcinoma in the mass also had carcinoma in several of the lymph nodes, and 4 of the 11 with teratoma in the mass had teratoma in the lymph nodes. Since the histopathological findings of the mass often parallel those of the lymph nodes, and since masses containing only fibrosis and/or necrosis cannot be ascertained with accuracy at operation, a complete retroperitoneal lymph node dissection is recommended in patients with a residual retroperitoneal mass.
Adolescent↗
Resolution of bony metastases after bilateral orchiectomy for carcinoma of prostate.
Resolution of multiple bony metastases after bilateral orchiectomy for carcinoma of prostate was documented by roentgenogram and scintigraphy. This marked improvement was correlated with a decline in serum acid phosphatase, disappearance of soft tissue tumor, and clinical improvement in the patient.
Adenocarcinoma↗
Efficient scheduling of cystoscopies in monitoring for recurrent bladder cancer.
Proper timing for repeated evaluations is difficult to assess. The authors analyzed scheduling of cystoscopy to monitor patients for detection of recurrent bladder cancer assuming that 1) minimizing tumor detection delay helps prevent cancer morbidities; 2) only limited numbers of cystoscopies are available; 3) prediction of recurrence or progression to invasive cancer is uncertain; 4) future tumors recur according to a Poisson process. Assumptions 3 and 4 permit estimation of each patient's recurrence rate. Thus, patients may be compared according to their relative risks of future tumors. With these assumptions, nonlinear optimization theory was used to calculate monitoring schedules for a model practice. Given 5.4 available visits per week per 100 patients, cystoscopy was recommended in 9-11 weeks for high-risk patients and in 30-40 weeks for low-risk patients, depending on stages, grades, and numbers of previous tumors. In contrast, standard cystoscopy was recommended in 13, 26, or 52 weeks, depending only on time elapsed since last recurrence. The calculated schedule implied an average detection delay for potentially invasive tumors of eight weeks, while standard practice led to detection delays of 11 weeks (38% worse). These results suggest that inclusion of each patient's tumor history in an optimization approach may improve follow-up care for patients who have superficial bladder cancers. This approach is being evaluated in a larger clinical setting.
Appointments and Schedules↗
Evaluation of nonlinear optimization for scheduling of follow-up cystoscopies to detect recurrent bladder cancer. The Bladder Cancer follow-up Group.
Standard recommendations for patients who have had superficial bladder cancer are inspection by cystoscopy quarterly for a year or two after tumor removal, then half-yearly and yearly. The authors assessed the potential for improvement in scheduling cystoscopies according to probabilistic optimization techniques. Eight hypothetical practices were created, based on retrospective analysis of 918 bladder-cancer-patient charts. Standard and alternative recommendations for the interval to next cystoscopy were compared. The alternatives were derived from patient-specific predictions of future tumor risks (based on the patient's prior recurrence rate and tumor stage and grade) and a nonlinear optimization approach to allocation of the same number of cystoscopies as were available for standard follow-up. The optimization proposed longer intervals between visits for low-risk patients and shorter intervals for high-risk patients. Overall, optimization reduced expected tumor detection delays by 30%, from 12.6 to 8.7 weeks. When optimization intervals were shorter than standard, cancer was found more often at subsequent cystoscopies (34% vs 27%, p less than 0.05), suggesting that the optimization was a better predictor of cancer recurrence. If reduction in tumor-detection delay is the goal of follow-up for recurrent cancers, then urologists can improve monitoring by using probabilistic optimization methods for scheduling cystoscopies. Further understanding of the accuracy of predictive models for bladder-cancer recurrence rates is desirable. Subsequently, the optimization method developed here may be tested prospectively.
Aftercare↗