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Biomedical subjects

J H Ross

Publications and source records attributed to J H Ross.

At least 19 recordsLinked to original sources

Could pesticide toxicology studies be more relevant to occupational risk assessment?

Pesticide toxicology study design has evolved from concern for oral exposure via food residues. The emphasis on the oral route does not generally apply to workers that are exposed primarily via the dermal route either handling pesticides or re-entering treated fields. As a result numerous assumptions about how oral toxicology results relate to dermal exposure must be made when conducting worker risk assessments. These assumptions introduce a high degree of uncertainty. Alternative toxicology study designs are suggested to reduce uncertainty when assessing risk. Because the dermal route is so important to characterizing occupational risk, methods to improve the accuracy of dermal absorption estimates are suggested, including the use of human subjects to study dermal absorption. Additional suggestions include tailoring dermal, oral and inhalation kinetic study designs to reflect worker exposure dosages. Suggestions are made to routinely conduct a single dose toxicity study patterned after the neurotoxicity study design to distinguish single dose effects and NOAELs from those resulting from multiple doses. Finally, interspecies pharmacokinetics studies are proposed to determine which toxicology study regimen of dosing best reflects intermittent worker exposure.

Administration, Inhalation↗

Biomonitoring of persons exposed to insecticides used in residences.

Pesticides used indoors inevitably result in some unintentional and unavoidable exposures of residents. Measured dosages of residents are well below toxic levels. Exposures (microg/kg-day) are substantially less and occur over a longer time than suggested by unvalidated estimates derived from previous extreme, conservative default assumptions based solely on environmental residues. Human chlorpyrifos exposures were monitored following three different types of applications: fogger, broadcast, and crack-and-crevice. Persistence of total residue on carpet was substantially greater than the persistence of transferable residue (microg/cm(2)). Low-level (microg/kg) exposures of family members persisted for periods of weeks to a month after pesticide use. Although few children who resided with their parents in pest-protected homes have been monitored, they eliminated more biomarker than their parents on a kg body weight-day basis when absorbed dosages (microg/kg-day) were derived from spot urine specimens corrected for volume by an age-specific creatinine correction. Ultimately environmental residues may become useful elements of predictive residential exposure models, but their potential contribution to indirect exposure assessments must include careful determination of residue availability for contact transfer to clothing or skin and biological validation. When environmental data from monitoring studies reported here were used to estimate residential exposure according to Residential Exposure Assessment Standard Operating Procedures (SAP meeting, 1997), measured exposures were substantially less than assessments. Experimental and situational monitoring of exposed persons is essential for meaningful and responsible predictive resident exposure model building.

Administration, Cutaneous↗

Stromal testis tumors in children: a report from the prepubertal testis tumor registry.

PURPOSE: Stromal testis tumors are rare and generally exhibit a benign behavior in prepubertal patients. We reviewed the Prepubertal Testis Tumor Registry to elucidate further the behavior of these tumors. MATERIALS AND METHODS: Epidemiological and clinical information on stromal testis tumors was compiled and reviewed from the Prepubertal Testis Tumor Registry. In addition, original pathology reports were requested for all patients registered as having undifferentiated stromal tumors. RESULTS: There were 43 patients registered with stromal tumors. Of the 21 patients with unspecified stromal tumors pathology reports were obtained on 11. Eight patients had truly mixed or undifferentiated stromal tumors. Mean patient age at presentation was 38 months (Leydig cell 70, Sertoli cell 52.5, juvenile granulosa cell 1.5 and mixed/undifferentiated 41.2). No patient with a Leydig cell, Sertoli cell or juvenile granulosa cell tumor had metastases at presentation or metastatic disease during an average 24.6 months of followup. One undifferentiated tumor demonstrated malignant behavior by presenting with metastatic disease. Pathological examination revealed a poorly differentiated tumor with extension into the adjacent tunica and frequent mitotic figures. While other stromal tumors displayed mitotic figures, none showed local invasion. CONCLUSIONS: Stromal testis tumors are rare. Data from the Prepubertal Testis Tumor Registry confirms the benign behavior of most of these tumors. However, undifferentiated stromal tumors may exhibit metastatic behavior. A high index of suspicion is appropriate when there are a large number of mitotic figures, the tumor is poorly differentiated or when local invasion is present in the primary tumor. Metastatic evaluation and close followup are warranted for this select group of patients.

Adolescent↗

Renal neoplasms in adult survivors of childhood Wilms tumor.

PURPOSE: Survivors of childhood Wilms tumor have been followed by large collaborative studies for approximately 31 years. In this time a number of second malignant neoplasms have been documented in these Wilms tumor survivors and they are at higher risk for such development compared with the general population. To our knowledge no renal neoplasms have been previously reported in patients successfully treated for Wilms tumor in childhood. MATERIALS AND METHODS: We reviewed the cases of 4 adults in whom Wilms tumor was treated in childhood by radical nephrectomy and adjuvant therapy and who presented to our institution with complex cystic or solid renal masses in the contralateral kidney. Parameters, including patient age at Wilms tumor diagnosis, Wilms tumor treatment modalities, age at second malignant neoplasm presentation and resected renal lesion pathology were outlined. A thorough literature review was performed to identify the development of renal malignancies as second malignant neoplasms in survivors of Wilms tumor in childhood. RESULTS: The International Society of Pediatric Oncology and National Wilms Tumor Study have followed patients treated for Wilms tumor for no greater than 31 years. Renal neoplasms, including 2 renal cell carcinomas, 1 oncocytoma and 1 atypical cyst, in the solitary remaining kidney of relatively young adults 34 to 50 years old who were treated for Wilms tumor greater than 31 years ago were successfully treated with partial nephrectomy at our institution. Neither the International Society of Pediatric Oncology nor National Wilms Tumor Study has identified renal cell carcinoma as a second malignant neoplasm in patients successfully treated for Wilms tumor. CONCLUSIONS: Our experience suggests that relatively young adults with a history of childhood treatment for Wilms tumor may be at increased risk for renal neoplasms at ages not yet achieved by those enrolled in large multicenter trials. This possibility should be considered when planning the long-term followup of these patients. The potential to develop this type of second malignant neoplasm again raises the clinical issue of performing a primary nephron sparing procedure in children presenting with Wilms tumor.

Adenoma, Oxyphilic↗

Laparoscopic cross-trigonal Cohen ureteroneocystostomy: novel technique.

PURPOSE: We describe a novel technique of laparoscopic transvesical cross-trigonal Cohen anti-reflux ureteroneocystostomy. MATERIALS AND METHODS: A 10, an 11 and a 32-year-old patient with symptomatic unilateral vesicoureteral reflux underwent laparoscopic cross-trigonal ureteral reimplantation. Two 5 mm. balloon tip ports were suprapubically inserted into the bladder. Using a transurethral resectoscope with a Collins knife a 4 to 5 cm. cross-trigonal submucosal trough was created from the refluxing ureteral orifice to the contralateral side of the bladder. The refluxing ureteral orifice and intramural ureter were completely mobilized intravesically, advanced transtrigonally and secured to the detrusor muscle at the apex of the trough with 3 deep interrupted sutures. The elevated mucosal flaps of the trough were suture approximated over the ureter to create a submucosal tunnel. All suturing was performed by freehand laparoscopic technique. RESULTS: Operative time was between 2.5 and 4.5 hours and blood loss was 10 to 50 cc. Adequate submucosal trough creation, ureteral extravesical mobilization and intravesical advancement, and bladder mucosal flap reapproximation were done to create a submucosal tunnel in all cases. Satisfactory transtrigonal anchoring of the neoureteral orifice to the detrusor muscle and mucosa was achieved with 3 stitches. Hospital stay was 2, 2 and 1 days in the 3 cases, and the Foley catheter remained in place for 3, 1 and 1 week, respectively. At 6 months reflux had resolved in 2 patients, while in 1 grade II reflux persisted, which was improved from grade IV preoperatively. All patients have remained infection-free without antibiotics. CONCLUSIONS: Laparoscopic transvesical cross-trigonal antireflux ureteral reimplantation is technically feasible. Intravesical laparoscopic suturing is possible. Potential advantages include a decreased hospital stay, decreased narcotic requirement and better cosmesis. Further experience is necessary to refine the technical nuances and evaluate outcomes compared to the open technique.

Adult↗

Conservatism in pesticide exposure assessment.

Three important factors are commonly encountered in exposure assessment that when combined could overestimate the exposure to pesticides by as much as two orders of magnitude. The three factors discussed are dermal absorption from laboratory animal studies, daily dose extrapolated from partial day monitoring, and nonbolus dose from dermal or inhalation exposure. Conservatism built into the process by each of these three factors is substantiated with available empirical data. The dose overestimation from these factors varies discriminatively by exposure scenarios and peculiarities of a given chemical. It is for this reason that a generic overestimation factor cannot be ascribed. Following the empirical illustrations, the authors conclude that the most effective approach for dealing with the problem is to generate the most appropriate data possible. This means producing human rather than laboratory animal dermal absorption data, conducting full-day exposure monitoring studies, and whenever feasible generating dermal rather than oral toxicology data (or alternatively data on both oral and dermal pharmacokinetics) in those cases where the dermal route predominates.

Animals↗

Pheochromocytoma. Special considerations in children.

Pheochromocytoma is a rare but important tumor in children. Appropriate evaluation and management are essential for a favorable outcome. Pheochromocytomas are more often multifocal and extra-adrenal in children when compared with adults. This pattern makes the diagnosis, localization, and surgical management more challenging. Nonetheless, the standard biochemical evaluation is usually diagnostic, and MR imaging is currently the best tool for tumor localization. The possibility of a familial syndrome must always be considered and should always be thoroughly evaluated when children present with a pheochromocytoma. Conversely, children with a familial syndrome should undergo annual screening for pheochromocytoma from a young age. Given the greater likelihood of a metachronous recurrence in children, consideration should be given to adrenal-sparing surgery in selected patients. When managed appropriately, the outlook for pheochromocytoma in children is excellent. Unfortunately, the uncommon malignant tumors are still difficult to treat. Perhaps the unique genetic characteristics of pheochromocytoma will ultimately be exploited in the management of the aggressive forms of this disease.

Adrenal Gland Neoplasms↗

Needlescopic surgery for cryptorchidism: the initial series.

PURPOSE: The aim of this study is to report the initial experience with needlescopic surgery (2-mm optics and instrumentation exclusively) for the cryptorchid testicle. METHODS: Ten patients (age 8 months to 37 years) underwent 12 needlescopic procedures: orchiopexy (n = 8), orchiectomy (n = 2), and diagnostic exploration with attempted excision of testicular remnant (n = 2). Two patients underwent bilateral needlescopic orchiopexy. Needlescopic (2 mm) optics and instrumentation were used exclusively in the pediatric patients. RESULTS: All procedures were completed successfully by needlescopic techniques. Mean surgical time was 110 minutes (range, 60 to 180 minutes), and blood loss was 6 mL (range, 0 to 20 mL). There were no intraoperative complications. All procedures were performed on an outpatient basis. In all 8 orchidopexies, the testis was successfully brought to a scrotal position. CONCLUSIONS: Needlescopic techniques allow safe performance of various procedures for a cryptorchid testicle. The cosmetic result is excellent.

Adult↗

Penile adhesions after neonatal circumcision.

PURPOSE: The appropriate management of penile adhesions in circumcised boys is unclear. An important consideration is whether adhesions resolve spontaneously. We studied the incidence of penile adhesions as a function of patient age to assess the natural history. MATERIALS AND METHODS: We evaluated all circumcised boys presenting to our pediatric urology clinic. A standard form was used to classify adhesions as grade 0-no adhesions, 1-fine adhesions to the corona, 2-adhesions covering less than 50% of the glans and 3-adhesions covering greater than 50% of the glans. All boys were evaluated by 1 of 2 pediatric urologists. Previous treatment of adhesions was assessed and skin bridges were also noted. RESULTS: We enrolled in our study 254 boys 1 month to 19 years 8 months old. Only 7 patients had a history of treatment of adhesion, of whom 3 had recurrent adhesions at evaluation. Patients were divided into groups based on age, including younger than 12 months (61), 13 to 60 (78), 61 to 108 (51) and 109 months old or older (64). In these groups we noted an adhesion rate of 71%, 28%, 8% and 2%, respectively. The rate of adhesions more severe than grade 1 was 30%, 10% and 0% in boys 12 months old or younger, 13 to 60 and 61 months old or older, respectively. The oldest patient with grade 3 adhesions was 31 months old. Skin bridges in 6 cases involved the circumcision line in 4. CONCLUSIONS: Penile adhesions develop after circumcision and the incidence decreases with patient age. Although there is debate on whether to lyse these adhesions manually, our findings suggest that adhesions resolve without treatment. Based on our results we do not recommend lysing penile adhesions, except perhaps those involving the circumcision line.

Adolescent↗

Pediatric urinary tract infection and reflux.

Urinary tract infections in children are sometimes associated with vesicoureteral reflux, which can lead to renal scarring if it remains unrecognized. Since the risk of renal scarring is greatest in infants, any child who presents with a urinary tract infection prior to toilet training should be evaluated for the presence of reflux. Children who may be lost to follow-up and those who have recurrent urinary tract infections should also be evaluated. The preferred method for evaluation of urinary reflux is a voiding cystourethrogram. Documented reflux is initially treated with prophylactic antibiotics. Patients who have breakthrough infections on prophylaxis, develop new renal scarring, have high-grade reflux or cannot comply with long-term antibiotic prophylaxis should be considered for surgical correction. The preferred method of surgery is ureteral reimplantation. A newer method involves injection of the bladder trigone with collagen.

Child↗

Estimation of dermal absorption using the exponential saturation model.

Estimates of dermal absorption are used in exposure assessment to calculate the internal dose of persons contacting pesticides and are a critical part of risk assessments. An exponential saturation model with lag time was validated against a classic dermal absorption study of 12 pesticides administered to human volunteers. The model gave dermal absorption estimates consistent with reported values in the literature. Moreover, this model gave more realistic estimates of the percentage of dermal absorption for some pesticides, which have special properties. In most submitted dermal absorption studies in animals, especially rats, "bound" skin residues (BSR) at treated skin sites were generally high when animals were sacrificed more than 24 h after the dose was administered. The direct addition of the total BSR as an absorbed dose would likely overestimate actual dermal absorption. From a well-conducted dermal absorption study, this model can be utilized to estimate maximum excretion of the administered dermal dose as a result of further absorption of bioavailable BSR. Resulting dermal absorption estimates are appropriate for regulatory purposes in the risk assessment of pesticides because they take into account the bioavailability of BSR while at the same time the estimates are not overly conservative.

Animals↗

Composition and role of tapetal lipid bodies in the biogenesis of the pollen coat of Brassica napus.

The composition of the two major lipidic organelles of the tapetum of Brassica napus L. has been determined. Elaioplasts contained numerous small (0.2-0.6 micron) lipid bodies that were largely made up of sterol esters and triacylglycerols, with monogalactosyldiacylglycerol as the major polar lipid. This is the first report in any species of the presence of non-cytosolic, sterol ester-rich, lipid bodies. The elaioplast lipid bodies also contained 34- and 36-kDa proteins which were shown by N-terminal sequencing to be homologous to fibrillin and other plastid lipid-associated proteins. Tapetosomes contained mainly polyunsaturated triacylglycerols and associated phospholipids plus a diverse class of oleosin-like proteins. The pollen coat, which is derived from tapetosomes and elaioplasts, was largely made up of sterol esters and the C-terminal domains of the oleosin-like proteins, but contained virtually no galactolipids, triacylglycerols or plastid lipid-associated proteins. The sterol compositions of the elaioplast and pollen coat were almost identical, consisting of stigmasterol > campestdienol > campesterol > sitosterol >> cholesterol, which is consistent with the majority of the pollen coat lipids being derived from elaioplasts. These data demonstrate that there is substantial remodelling of both the lipid and protein components of elaioplasts and tapetosomes following their release into the anther locule from lysed tapetal cells, and that components of both organelles contribute to the formation of the lipidic coating of mature pollen grains.

Amino Acid Sequence↗

Risk of contralateral hydrocele or hernia after unilateral hydrocele repair in children.

PURPOSE: Recent laparoscopic studies indicate a high incidence of a contralateral open internal ring in children undergoing unilateral hydrocele or hernia repair, raising the question of whether routine contralateral exploration should be done. Data on the long-term risk of clinical contralateral hernia or hydrocele after unilateral hydrocele repair are limited. To address this question we performed long-term followup in patients who underwent unilateral hydrocele repair. MATERIALS AND METHODS: We followed patients who previously underwent unilateral hydrocele repair performed by one of us before 1997. Patients were interviewed by telephone and encouraged to return to one of us or their pediatrician for evaluation. RESULTS: Of the 101 patients who fulfilled study inclusion criteria 85 who were 5 to 107 months old (median age 37) at the original surgery were successfully contacted, including 45 examined by one of us or a pediatrician and 40 followed by telephone interview only. Contralateral hydrocele or hernia developed in 6 of the 89 patients (7%) 6 to 15 months (median 12) postoperatively. The remaining 79 patients have been recurrence-free for 6 to 153 months (mean 44, median 37). Of the patients 5 of 32 are (15%) and 1 of 53 (2%) who underwent left and right hydrocele repair, respectively, had contralateral recurrence. CONCLUSIONS: The risk of a clinically evident contralateral hydrocele or hernia after unilateral hydrocele repair is approximately 7%. We do not recommend routine contralateral exploration in children undergoing unilateral hydrocele repair.

Child↗

The effects of blood lactate concentration on perception of effort during graded and steady state treadmill exercise.

Studies have reported that ratings of perceived exertion (RPE) are a valid tool for exercise prescription when blood lactate concentration (BLC) is used as the intensity criterion. However, few have studied the relationship between RPE and BLC during commonly used graded exercise tests (GXTs) and simulated exercise training. The purpose of this study was to determine if the RPE: BLC relationship is transferable across GXTs and a steady state exercise trial (SST). Thirteen healthy males (25+/-5.3yrs) completed two maximal treadmill tests (Bruce and Balke protocols) followed by a SST which consisted of approximately 8 minutes of exercise at each of two intensities (approximately 40% and 70% maximal heart rate reserve). BLCs and other physiological measures were compared at matched RPEs across the GXTs and SST trial at each exercise intensity using a two-way repeated measures ANOVA. There were no significant differences in BLC at a matched RPE across the exercise trials at the lower exercise intensity with the BLCs being 1.5+/-0.3, 1.6+/-0.6 and 1.3+/-0.3 mM, respectively. However, at the higher exercise intensity BLCs were significantly lower during the Balke GXT compared to the Bruce GXT and SST (1.8+/-0.6, 2.8+/-1.8 and 3.0+/-0.8 mM, p < 0.05). These results suggest that the RPE: BLC relationship may be protocol dependent during graded exercise testing as it was only transferable from the Bruce GXT to the exercise training setting at intensities in the typical prescription range of 50-85% of VO2max.

Adult↗

Surgical considerations for patients with Wilms' tumor.

Despite the advances in multimodal treatment of Wilms' tumor, surgical staging and tumor resection remain a central component of therapy. Although standard approaches are available through multicenter studies, such as the NWTS and SIOP, controversy exists regarding several aspects of surgical management. Recent data call into question the need for contralateral exploration in the era of modern imaging. Various methods are available for managing caval tumor thrombus. Bilateral Wilms' tumor requires a special surgical strategy. The surgeon plays a key role in determining whether preoperative chemotherapy should be used to facilitate surgical resection. The role of partial nephrectomy is still being defined. And finally, surgery plays an important role in the management of tumor recurrence. Surgeons must be fully aware of the data and philosophical issues that pertain to these areas if they are to fulfill their role in the multidisciplinary team caring for children with Wilms' tumor.

Child↗