Search

Gary Jerkins,1 Jack V Greiner,2,3 Louis Tong,4– 6 Jacqueline Tan,7 Joseph Tauber,8 Ali Mearza,9,10 Sruthi Srinivasan11 1Advancing Vision Research, LLC, Nashville, TN, USA; 2Clinical Eye Research of Boston, Boston, MA, USA; 3Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 4Singapore National Eye Center, National University of Singapore, Singapore; 5Singapore Eye Research Institute, Singapore; 6Duke-National University of Singapore Medical School, Singapore; 7University of New South Wales, Sydney, NSW, Australia; 8Tauber Eye Center, Kansas City, MO, USA; 9Imperial College Healthcare NHS Trust, London, UK; 10Ophthalmic Consultants of London, London, UK; 11Alcon Research, LLC, Johns Creek, GA, USACorrespondence: Gary JerkinsAdvancing Vision Research, LLC, Nashville, TN 37205, USATel +1 615-502-2871Fax +1 615-915-1825Email drjeyeguy@garyjerkins.comPurpose: The aim of this study was to compare the efficacy of two lipid-based lubricant eye drops in patients with lipid-deficient dry eye.Methods: This Phase IV, multicenter, prospective, double-masked study enrolled adults (aged ≥ 18 years) who had a tear film breakup time (TFBUT) of ≤ 15 seconds(s), and unanesthetized Schirmer I test of ≥ 3 mm to ≤ 12 mm in at least one eye, at both screening and baseline visits. Eligible patients (n=231) were randomized (1:1) and received either Systane® Balance (SYSB; n=117) or Refresh® Optive Advanced (RFO-Ad, n=114), four-times a day, for 35 days. The primary endpoint was non-inferiority for change from baseline in TFBUT at Day 35 (non-inferiority was established if the lower limit of the 95% confidence interval (CI) for the difference between the treatment groups was > – 1.0 s); secondary endpoints (test of superiority) were change in TFBUT and global ocular discomfort visual analog scale (VAS) score at Day 35. Other endpoints included the impact of dry eye on everyday life (IDEEL) treatment satisfaction scores (inconvenience and effectiveness) and safety.Results: At Day 35, the mean change from baseline in TFBUT was 0.998 s in the SYSB and 0.868 s in the RFO-Ad groups with a treatment difference: 0.130 s; (95% CI − 0.34, 0.60; P< 0.0001) demonstrating non-inferiority of SYSB to RFO-Ad. The global ocular discomfort VAS scores improved in both groups, with a mean change from baseline of – 9.7 and – 8.8 in SYSB and RFO-Ad groups (treatment difference – 0.8; P=0.62), respectively. No meaningful difference was observed in IDEEL treatment effectiveness and treatment inconvenience scores between SYSB vs RFO-Ad (P> 0.05 for treatment difference). Both treatments were well tolerated.Conclusion: SYSB lubricant eye drops were non-inferior to RFO-Ad for improvement in TFBUT in patients with lipid-deficient dry eye. Both lubricant eye drops improved TFBUT and ocular discomfort scores in patients with lipid-deficient dry eye.Keywords: dry eye, lipid-deficient, evaporative dry eye, lubricant eye drops, non-inferiority

Gary W Jerkins,1 Guruprasad R Pattar,2 Shane R Kannarr3 1Advancing Vision Research, Nashville, TN, USA; 2The Eye Care Institute, Louisville, KY, USA; 3Kannarr Eye Care, Pittsburg, KS, USACorrespondence: Gary W JerkinsAdvancing Vision Associates, 4306 Harding Pike, Nashville, TN 37205, USATel +1 615 502-2871Email drjeyeguy@garyjerkins.comAbstract: Keratoconjunctivitis sicca (KCS) is a multifactorial disease characterized by tear hyperosmolarity, inflammation, and ocular surface damage. Cyclosporine A (CsA) is used as an effective disease-modifying agent to improve the signs and symptoms of KCS by reducing inflammation, which interferes with tear production. This review provides an overview of efficacy, safety, and limitations of currently marketed topical CsA formulations—including CsA ophthalmic emulsion, cationic nanoemulsion, and aqueous nanomicelles—and highlights newer technologies for controlled ocular delivery of CsA and their clinical implications. Long available emulsion formulations of CsA are oil-based and have several limitations, including slow onset of efficacy and low intraocular penetration and bioavailability. Aqueous CsA nanomicelle carriers produce rapid improvement in objective signs of KCS such as corneal and conjunctival staining as early as 4 weeks and have acceptable safety profiles. CsA formulations using semifluorinated alkanes or polyaphrons are currently in clinical development, having recently completed Phase 2 studies. Other carriers for CsA currently in the preclinical phase include microemulsions, polymeric aqueous and lyophilized micelles, and hydrogels; these novel formulations have yet to undergo clinical trials. Formulations that improve tissue availability of CsA may be beneficial in clinical practice by providing faster onset of relief and improving patient adherence.Keywords: cyclosporine A, keratoconjunctivitis sicca, emulsion, nanomicelles, OTX-101

Purpose: Dry eye disease is a multifactorial disorder that affects the ocular surface, with symptoms including ocular irritation, impaired vision, and pain. Nicotinic acetylcholine receptor (nAChR) agonists are novel treatments for dry eye disease; this study investigates the nAChR agonist OC-02 (simpinicline solution) as an aqueous nasal spray., Methods: PEARL (Clinical Trial to Evaluate the Efficacy of OC-02 Nasal Spray on Signs and Symptoms of Dry Eye Disease) was a Phase II study that evaluated the efficacy and safety of OC-02 (simpinicline solution) nasal spray (OC-02 SNS) in adult patients with dry eye disease. Patients ≥22 years of age were eligible if they had an Ocular Surface Disease Index score ≥23, corneal fluorescein staining score ≥2 in >1 region or ≥4 for all regions, or Schirmer test score (STS) ≤10 mm; there were no restrictions on eye dryness score (EDS). Patients (N = 165) were randomly assigned 1:1:1:1 to vehicle (control; n = 42) or OC-02 SNS (0.11 mg, 0.55 mg, or 1.1 mg; n = 41 per group) and received a single dose of study drug (100 µL using a nasal spray atomizer) at visit 1 and visit 2 (15-19 days after visit 1). Primary efficacy outcomes were change in the STS from baseline to immediately after treatment administration (visit 1) and change in the EDS from before to 5 minutes after treatment during controlled adverse environment exposure (visit 2)., Findings: Baseline demographic and ocular clinical characteristics were similar across all groups. Single-dose OC-02 SNS improved the signs and symptoms of dry eye disease. For the STS, statistically significant and dose-dependent improvements were found from before to after treatment with OC-02 SNS versus vehicle (least-squares mean change from baseline: vehicle, 3.0 mm; 0.11 mg OC-02 SNS, 9.0 mm; 0.55 mg, 17.5 mm; and 1.1 mg, 19.6 mm). For EDS, statistically significant and dose-dependent improvements were found from before to 5 minutes after treatment with higher doses of OC-02 SNS versus vehicle (least-squares mean change from baseline: vehicle, -6.5; 0.11 mg OC-02 SNS, -9.4; 0.55 mg, -17.4; and 1.1 mg, -20.7). OC-02 SNS was well tolerated: only 2 ocular adverse events were reported (eye pruritis and keratitis), and the most common nonocular events were cough and throat irritation., Implications: Single-dose OC-02 SNS over a range of doses immediately and significantly increased tear production and improved eye dryness. Together with previous studies of OC-01 (varenicline solution) nasal spray, our findings suggest that agonist stimulation of nAChRs in the nasal cavity is a valid and effective mechanism to elicit natural tear production in patients with dry eye disease., Clinicaltrials: gov identifier: NCT03452397., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Pharmacogenetic (PGx) testing is a tool to identify patients at a higher risk of adverse events or treatment failure. The concern for unwanted side effects can limit medication adherence, particularly in children and adolescents. We conducted a pragmatic study to evaluate the acceptability and feasibility and gather pilot data on the utility of PGx testing in a child and adolescent psychiatry clinic. Both physicians and families participated in the study and answered pre-survey and post-survey questionnaires to examine their attitudes toward PGx testing. Patients were randomized into implementation (N = 25) and control groups (N = 24) and underwent PGx testing at the beginning or end of the study, respectively. Clinical consult notes with genotype-guided recommendations were provided to physicians for their consideration in clinical decisions. Patient-reported symptom severity and antidepressant-related side effects were assessed at baseline and for 12 weeks. Both participating physicians and families agreed that PGx testing is a useful tool to improve medication selection. The time from sample collection to having PGx test results was ~ 10 days and 15 days to having consult notes available, which may have impaired test utility in clinical decision making. There were no differences in any clinical end point between the implementation and control arms; however, there were higher antidepressant side effect scores for CYP2D6 poor and intermediate metabolizers after the eighth week of treatment. Our findings revealed benefits and pitfalls with the use of PGx testing in the real-world clinical setting, which may inform the methodology of a larger trial focused on outcomes., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Purpose: To evaluate the safety and effectiveness of the intranasal tear neurostimulator (ITN) in improving dry eye symptoms assessed in a controlled adverse environment (CAE®)., Methods: Study 1: Multicenter, subject-masked, randomized-sequence, crossover design. Single intranasal (active) and extranasal (control) ITN administration during CAE exposure. Study 2: Single-arm, open-label design. Intranasal ITN administration ≥2 times/day for 45 days, CAE assessment at days 0 and 45. In both studies, upon CAE entry, and every 5 min thereafter, subjects assessed eye dryness score (visual analog scale, 0-100 mm; EDS-VAS), and ocular discomfort score (ODS; Ora Calibra™, 0-4), for ≈2 h. Study 1: when ODS was ≥3 at 2 consecutive timepoints, subjects applied ITN intranasally or extranasally for ≈3 min, and again when achieving the same ODS criteria in randomized sequence. Study 2: days 0 and 45, ITN was applied for ≈3 min employing the same ODS criteria as Study 1., Results: Study 1: Significantly greater pre- to post-application reductions in mean [SEM] EDS (-16.5 [1.7] vs -3.1 [1.7], P < 0.0001) and ODS (-0.93 [0.08] vs -0.34 [0.08], P < 0.0001; n = 143) with intranasal vs extranasal stimulation. Study 2: On day 0 (n = 52) and day 45 (n = 48), significant pre- to post-application reductions in mean [SEM] EDS (-15.9 [2.7] and -15.2 [2.4]; P < 0.0001), and ODS (-1.3 [0.2] and -1.3 [0.1]; P < 0.0001). Few device-related adverse events were reported, none serious., Conclusions: Acute symptom relief is significant with the ITN and remains undiminished after daily use., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the clinical effects of using fixed (four times daily [QID]) versus as-needed (PRN) dosing of an artificial tear product (polyethylene glycol/propylene glycol [PEG/PG]; Systane Ultra) in individuals with dry eye disease., Methods: In this prospective, multicenter, observer-masked, active-control, parallel-group trial, participants were randomized (1:2 allocation) to receive 1 drop of PEG/PG QID (n = 34) or PRN (n = 63) for 28 days. The primary endpoint was change from baseline in the total ocular surface staining (TOSS) score (according to the Oxford scale) at day 28., Results: At day 28, the change from baseline in least squares mean (LSM) TOSS scores for QID and PRN groups were -1.19 and -0.94, respectively (treatment difference [TD]: -0.26; 95% confidence interval [CI]: -∞ to 0.21; P = 0.184); superiority of QID versus PRN dosing was not established, as the upper limit of one-sided 95% CI for TD was not <0 (prespecified limit). At day 28, for QID and PRN groups, the LSM change from baseline in Impact of Dry Eye on Everyday Life (IDEEL) scores was symptom-bother, -7.0 and -2.94 (TD: -4.06, P = 0.037); treatment effectiveness, 2.43 and 0.16 (TD: 2.28, P = 0.278); and treatment-related inconvenience, -11.56 and -2.77 (TD: -8.8, P = 0.996), respectively. Incidence of adverse events was low (≤3.2%) in both the groups; no serious adverse events were reported., Conclusions: QID dosing of PEG/PG was not superior to PRN dosing in terms of ocular staining. The IDEEL symptom-bother score favored QID dosing, suggesting that regular use of artificial tears may provide better symptomatic relief than PRN use. (ClinicalTrials.gov number, NCT02446015.).

Objectives: To examine the incidence of postoperative ventriculoperitoneal shunt infections in patients after augmentation cystoplasty., Methods: We retrospectively reviewed the charts of 21 patients with a ventriculoperitoneal shunt who had bladder augmentation (18 ileal and 3 ileocecal) with attention to the preoperative urine culture, perioperative antibiotics, and the length of time drains were maintained. The abdominal end of all shunts was wrapped in an antibiotic-soaked sponge during the procedure. All patients had at least 1 year of follow-up., Results: Seven patients (33%) had culture proven, preoperative urinary tract infections. All patients received at least 24 hours of preoperative and 48 hours of postoperative antibiotics. No postoperative shunt infections occurred during the study period., Conclusions: The incidence of postoperative ventriculoperitoneal shunt infections after augmentation cystoplasty can be kept low when prophylactic antibiotics and short-term drains are used.

Purpose: We evaluated the safety and efficacy of emergency exploration of neonatal torsion., Materials and Methods: We retrospectively reviewed the charts of 27 neonates (30 affected testicles) in a 13-year period., Results: Of the 10 testicles that were explored and fixed within 6 hours of discovery 2 (20%) were normal at physical examination at 1 year of followup. Of the remaining 20 testicles 19 were removed. One patient was lost to followup after orchiopexy. No operative or perioperative complications were associated with emergency exploration., Conclusions: Emergency exploration of neonatal torsion is safe and prudent, and may result in higher testicular salvage rates. Given reports of contralateral torsion, we also recommend contralateral orchiopexy.

The clinical presentation of hyperreactio luteinalis can mimic ovarian hyperstimulation. Historically, though, the former most often leads to unnecessary surgery whereas the latter is treated supportively. We present a case of a 32-year-old woman who was initially seen with markedly enlarged multicystic ovaries, ascites, and pleural effusions in the tenth week of a spontaneously conceived gestation. Despite a noniatrogenic cause, the patient received supportive management, as would be given with ovarian hyperstimulation syndrome. Making the distinction between hyperreactio luteinalis and ovarian hyperstimulation syndrome has important consequences for diagnosis and management.

Previous studies have established normal penile length for patient age and stage of sexual development. To our knowledge penile length has only been determined to date by measuring the stretched distance from the symphysis to the glans tip. Pilot studies at our institution showed that ultrasound corpora cavernosa length determinations were possible using a 7.5 MHz. linear transducer probe. To determine whether ultrasound is a more accurate modality in assessing penile length, male subjects 0 to 24 months old with normal penile anatomy and palpably descended testicles were enrolled in a prospective analysis. Longitudinal ultrasound images of the flaccid penis were obtained from the dorsal surface. The whole corporeal bodies were easily imaged and measured. In a blinded fashion a separate investigator performed a conventional stretched penile length determination. A total of 27 male subjects 1 week to 22 months old was evaluated and 2 were excluded. Corpora cavernosa measurements using ultrasound revealed a mean length of 32.3 +/- 4.7 mm. (range 22.4 to 44.9). Stretched penile lengths of the same subjects revealed a mean length of 46.8 +/- 8.2 mm. (range 31 to 63). Circumcision status (p = 0.036) and age (p < 0.001) significantly correlated with stretched length determinations. Ultrasound measurements did not significantly vary with patient circumcision status or age. Penile length and race were not correlated when using stretched or ultrasound measurements. Ultrasound determination of corporeal body length is possible in young subjects. From infancy to age 22 months ultrasound measurements are not significantly affected by age or the presence of foreskin. Our experience suggests that corporeal body evaluation by ultrasound may offer a more accurate assessment of functional penile length.

We report significant blunt renal injury resulting from 3 traumatic events in 2 boys with the prune-belly syndrome. Manifestations of the syndrome influenced the clinical and radiographic assessment of the urinary tract injuries. Nonoperative management resulted in excellent outcomes without long-term sequelae.

Bed-wetting is a frustrating problem experienced by a significant number of children. It is the role of the physician to exclude serious underlying problems and, at the same time, educate the family concerning treatment options that may be best suited to their child. Once parents and child have a better understanding of the problem and realize that the outlook for nighttime bladder control is excellent, it is easier to start long-term care.

An unusual late complication of an abdominal gunshot wound is presented. It consisted of an acute hydronephrosis of the left kidney by a BB-type bullet that migrated into the ureter of a 11-year-old boy 1 month after he was injured in the left flank, causing its complete obstruction. A percutaneous nephrostomy was performed and, with the help of a basket-type catheter, the bullet was removed. To our knowledge this is the first case reported of this rare complication treated by this technique.

The ability of computed tomographic (CT) criteria to predict the potential for resection with renal salvage in unilateral Wilms' tumor was evaluated retrospectively in 10 children given preoperative treatment for initially inoperable disease. Criteria were (a) tumor involving only one pole and occupying less than one-third of the kidney, (b) functioning kidney, (c) no invasion of collecting system or renal vein, and (d) clear margins between tumor, kidney, and surrounding structures. Review of preoperative CT scans correctly predicted nonsalvageability (as assessed by surgicopathologic findings) in seven cases. Sufficient pathologic data were lacking to confirm positive CT predictors in one case. One patient was rated resectable with salvage on surgicopathologic review, but not by CT criteria, and in one case, a prediction could not be made. The potential for renal salvage may be greater in samples with smaller initial tumor size, and addition of other imaging modalities might enhance the accuracy of prediction. Further studies are needed to assess the feasibility of prospective trials evaluating the risks and benefits of partial nephrectomy in unilateral Wilms' tumor.

The ratio of urinary calcium (UCa)/urinary creatinine (UCr) concentrations (mg/mg) during calcium loading has been used to diagnose hypercalciuric states in adults. The UCa/UCr ratios have been examined before and after an oral dose of calcium in 48 healthy children following five days of abstinence from dietary milk products. No differences in UCa/UCr ratios were observed between sexes, races, or age groups. UCa/UCr ratio before the calcium dose was 0.09 +/- 0.12 (mean +/- 2 SD) and increased to 0.12 +/- 0.15 in urine samples collected for four hours after the calcium load. A direct relationship between UCa/UCr ratio and urinary sodium (UNa)/UCr ratio was observed (r = .57, P less than .01). In six children, calcium loading studies were repeated without prior restriction of dietary calcium. Dietary calcium intake before the calcium loading had little effect upon UCa/UCr ratio before the calcium in these six children (0.068 vs 0.08); however, UCa/UCr values after the calcium load were significantly lower (0.08 vs 0.15) when no dietary calcium restriction preceded the calcium-loading study. These data may allow characterization of renal hypercalciuria and gastrointestinal hyperabsorption of calcium in children with urolithiasis.

Ureteropelvic junction obstruction in an incomplete duplex system is seen infrequently. This case represents an unusual presentation of such an obstruction. Recommendations are made for preoperative evaluation and surgical management of these patients.

A patient with severe cyclophosphamide cystitis was treated with intravesical silver nitrate instillation to control bleeding. This resulted in apparent reflux and extravasation of the silver nitrate solution with secondary retroperitoneal inflammation. Subsequently, the patient required treatment for a small, fibrotic bladder with persistent reflux. The precautions and recommendations for treatment of such difficult patients are discussed.

All physicians evaluating a painful red eye in a contact lens wearer should consider the diagnosis of Acanthamoeba keratitis. Although it remains relatively rare, the incidence of this infection is on the rise. Clues to the correct diagnosis include a corneal abrasion that fails to heal appropriately, pain out of proportion to the clinical findings, and a history of poor contact lens hygiene. Prompt recognition and appropriate ophthalmologic intervention can improve the visual outcome for patients with this devastating corneal infection.

Urinary calcium excretion was assessed in 83 consecutive children with gross or microscopic hematuria in whom the presence of proteinuria or urinary-tract infection had been excluded. Twenty-three children had hypercalciuria. Clinical features that were more commonly associated with hypercalciuria included gross hematuria and a family history of urolithiasis. No clinical or pathological basis for the hematuria was determined in 22 of the 23 children with hypercalciuria or in 38 of the 60 children with normal calcium excretion. Urolithiasis developed in two children with hypercalciuria during the period of study. Oral calcium-loading tests were performed in all 23 children with hypercalciuria. Absorptive hypercalciuria was demonstrated in 10 children, whereas 13 had renal (fasting) hypercalciuria. Hematuria resolved during anticalciuric therapy in 20 of the 23 patients with hypercalciuria. We conclude that determination of urinary calcium excretion is warranted in the routine evaluation of children with hematuria.

Since 1976, 23 patients with cyclophosphamide-induced cystitis were treated. These patients presented with a variety of urinary problems, including incontinence, hematuria and vesicoureteral reflux. Vesicoureteral reflux was found in 9 patients, hydronephrosis in 4 and a contracted fibrotic bladder in 3. Of the 23 patients 18 had undergone a combination of radiation and cyclophosphamide therapy. Based on this experience a general outline is developed for evaluation and treatment of patients with cyclophosphamide-induced cystitis and its potentially severe complications.

The pathogenetic roles of idiopathic renal hypercalciuria and absorptive hypercalciuria in children with urolithiasis have not yet been determined. Oral calcium loading studies were performed in 21 children with unexplained calcareous urolithiasis. Thirteen children, aged 20 months to 17 years, were found to have renal hypercalciuria after an overnight fast (urinary calcium-urinary creatinine [UCa/UCr] ratio in milligrams, greater than 0.21). Four children were found to have absorptive hypercalciuria. In this group, fasting UCa/UCr values were normal (SEM, 0.12 +/- 0.02); however, UCa/UCr values were elevated (SEM, 0.31 +/- 0.01) after the oral calcium load. Serum parathyroid hormone values were normal in all children with hypercalciuria. Urinary calcium excretion was normal in four patients. These data indicate that hypercalciuria may frequently occur in children with urolithiasis and that detailed metabolic evaluation is warranted in children with kidney stone disease.

Priapism has been reported to occur in 2 to 5 per cent of patients with sickle cell disease. Recently, creation of a percutaneous fistula between the glans penis and the corpora cavernosa has been applied widely in the management of patients with priapism, except in those cases of sickle cell anemia. Reported failures of such shunting procedures in the sickle cell patient has perhaps unduly denied surgical benefits to that population. We have managed successfully 5 such children with sickle cell anemia and priapism without complications by creation of a fistula between the glans penis and the corpora cavernosa. Our treatment plan is presented, which includes early shunting should initial nonoperative treatment fail.

If following posterior urethral valve fulguration a unilateral nonfunctioning or poorly functioning kidney remains, nephroureterectomy is the customary method of management. The distal ureter of such renal units can serve as a means of salvage for complications resulting from surgery on the ureter serving the remaining solitary functioning renal unit. We present 2 cases of posterior urethral valves where planned preservation of the distal ureter of a nonfunctioning kidney allowed salvage of such complications. We advocate preserving the ureter of a nonfunctioning renal unit if possible until the fate of the solitary functioning kidney and ureter is clear. This approach can be applied to other aspects of pediatric urologic reconstructive surgery.

We studied 35 children with voiding dysfunction and detrusor-sphincter incoordination. More than 90 per cent of these patients had a history of repeat urinary tract infections, and medication and surgical treatment of the voiding dysfunction had failed. Of the patients 22 (63 per cent) experienced significant improvement or resolution of the voiding dysfunction when biofeedback was used to teach normal bladder sphincter coordination as part of the over-all treatment regimen. A review of our experience with these patients indicates that with proper patient selection an even higher rate of success may be possible.

Ossifying renal tumor of infancy is a rare lesion, with only 2 cases reported in the literature. We report an additional case, and review its presentation and histological findings.

Cell-mediated immunity was assayed in 18 patients with a histologic diagnosis of carcinoma of the prostate and in 10 control patients with benign prostatic hypertrophy. In vivo cell-mediated response was assayed by intradermal skin testing to a battery of five delayed hypersensitivity antigens. In vitro cell-mediated immunity was studied by lymphocyte transformation using both heterologous and autologous "serums" and nonimmune rosette formation. Lymphocyte transformation studies were carried out using both specific antigens (Dermatophyton and streptokinase-streptodornase) and a nonspecific mitogen (phytohemagglutinin). Nonimmune rosette formation was performed under numerous temperature ranges. A defect in cell-mediated immunity was found in patients with carcinoma of the prostate. Skin tests demonstrated a significantly increased incidence of energy in cancer patients. Mitogen-induced lymphocyte transformation was significantly depressed when autologous serum from patients with carcinoma of the prostate was utilized in the procedure. It is concluded that defect in cell-mediated immunity does exist in patients with carcinoma of the prostate. This defect is expressed in vivo and in vitro and seems to be mediated by a serum factor.

Five children were evaluated for painless hematuria; currently recommended diagnostic studies were unsuccessful in determining a diagnosis. A renal calculus subsequently was passed or detected radiographically in each child from 14 to 20 months after the initial evaluation. Hypercalciuria was then demonstrated by quantitation of 24-hour urinary calcium excretion or by measurement of urinary calcium/creatinine ratio. Calculi and hematuria have not recurred following thiazide therapy. We infer that idiopathic hypercalciuria was a probable cause of the unexplained painless hematuria.

Nephroblastoma and renal stone disease are seen infrequently in children. We report on a 2-year-old girl with bilateral nephroblastoma and a simultaneous staghorn calculus in 1 kidney.

Serum from 20 children with urinary tract infections and proved cystitis cystica has been examined for antibody to a panel of established cell lines derived from normal urothelium and transitional cell carcinomas of the bladder. Antibody-dependent cytotoxicity was measured with serial dilutions of patient serum and lymphocytes from normal healthy adults as effector cells. The reaction was quantitated by the release of 51chromium from labeled target cells. The patients were grouped according to the duration of symptoms, the presence or absence of reflux, and the presence or absence of upper tract changes or scarring. No differences between test and control subjects were detected.

Condyloma acuminatum has been recognized as venereal disease in adults but it has not always been similarly identified in children. We review our experience with 30 children with condylomata acuminata. Of the 14 children evaluated more than half have been determined to have a sexual etiology for the lesion. Recommendations for evaluation and treatment of children with condylomata acuminata are reviewed.

Forty-one patients with esodeviation (82 eyes) were subjected first to 1% tropicamide and retinoscopy and then to retinoscopy after the use of 0.5% to 1% atropine sulfate in children with esodeviation up to the age of 5 years. The ages ranged from 2 months to 5 years, and the esodeviation ranged from 5 to 50 diopters (D). There were 20 male and 21 female patients. The average difference in the cycloplegia showed +.80 D more hyperopia with atropine than with tropicamide therapy. This was believed to be important, particularly in the young age group with esodeviation.

The hypertelorism-hypospadias syndrome has been reported previously in 19 affected male patients. In addition, 21 affected boys in 16 families have been evaluated at our center. Genitourinary anomalies other than hypospadias were observed frequently and included cryptorchidism, vesicoureteral reflux and minor upper urinary tract variations. An increased incidence of other developmental defects involving major organ systems also was observed. Since urologists are among the first physicians to evaluate these children, they should recognize this syndrome as an indication to initiate a thorough multisystem evaluation.

A 22-month-old child with a large cyst of Gartner's duct suffered from recurrent episodes of urinary retention. Excision of such large symptomatic cysts has been recommended in the past. Marsupialization is discussed as an alternative to extensive excision.

Cutaneous vesicostomy has proved to be a useful form of temporary diversion in children. We report our experience with 35 patients who underwent diversion for either lower tract dysfunction or obstruction. In only 1 child did vesicostomy appear to be of questionable value in adequately draining the upper urinary tracts. Renal functional improvement or stabilization was observed in the remaining 34 children. Complications occurred in 14 patients, with urinary tract infections of a clinically serious nature being observed in 6. Our experience tends to confirm vesicostomy to be an effective, simple and easily reversible means to treat selected conditions in infants and children. Complications are encountered but they have been managed effectively.

Children with posterior urethral valves and significant changes in the upper urinary tracts generally respond to initial fulguration of the valves and decompression of the bladder. Infrequently, a higher grade of obstruction of the ureters will develop after initial treatment. We report on 2 such children with this particular clinical course and discuss the management. The response of our patients indicates that acute obstruction at the ureterovesical junction is, in some cases, temporary and may not require longer term supravesical diversion procedures for proper management.

The indwelling ureteral stent recently introduced by Cook offers relative ease of placement with a self-curling end which prevents migration down the ureter. We have seen 4 cases of proximal migration of these stents. The reasons for this event are described. Our experience suggests the placement of a suture in the distal portion of the catheter to allow retrieval of the catheter should migration occur.

During the last 19 years 40 girls with urethral prolapse have been seen at our medical center. Treatment has ranged from nonoperative approaches to excision of the prolapsed urethra. A comparison of the treatment modalities indicates that patients undergoing early local excision of the prolapse have the lowest complication rate and shortest hospital stay.

A prospective study was established to identify the incidence of vesicoureteral reflux in the siblings of patients with reflux. Of 78 patients with reflux 104 siblings were screened with an awake voiding cystogram and 34 (32 per cent) were found to have reflux. Of these 34 siblings 25 (73 per cent) had no abnormal voiding symptoms or history of urinary tract infection. The highest incidence of reflux was found in the siblings of those patients with radiographic evidence of renal scarring. Early detection and followup in this high risk group may be a vital tool in determining more about the natural history of vesicoureteral reflux and its relationship to renal damage.

Our clinical experience with 47 pediatric patients with stones is reviewed. Surgical therapy was standard with successful stone manipulation in 12 of 13 patients. In 91 per cent of our patients factors causing or predisposing to stone disease were discovered. A thorough metabolic evaluation, including an oral calcium loading test in 20 children, proved to be helpful. A new patient subgroup relating unexplained hematuria to eventual stone formation is described. Our protocol for metabolic evaluation and recommendations for treatment based on the results of such an evaluation are given. We have found the metabolic evaluation of the child with stones meaningful and particularly helpful in planning subsequent therapy for these patients.