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Biomedical subjects

C S Cooper

Publications and source records attributed to C S Cooper.

At least 37 records · Page 2Linked to original sources
PubMed2000

Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.

Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.

Adolescent↗
PubMed2000

Long-term followup of endoscopic incision of ureteroceles: intravesical versus extravesical.

PURPOSE: Endoscopic incision was performed as the initial therapy for ureteroceles in children presenting to our institutions between 1985 and 1990. To assess the long-term efficacy of this treatment modality we reevaluated the outcome of these patients. MATERIALS AND METHODS: Parameters reviewed included patient age at surgery, position of the ureterocele, a duplex system, preoperative and postoperative reflux, and the need for additional operations. Statistical analysis consisted of chi-square and Wilcoxon's rank sum tests. RESULTS: Of the patients 22 had intravesical and 22 had extravesical ureteroceles. Average age at initial surgery was 1.9 +/- 3.7 years with average followup of 7.2 +/- 3.1 years. A second operation was required in 18 cases (41%), which was significantly more likely for an extravesical ureterocele (18% versus 64%, p = 0. 002), a duplex system (p = 0.026) or preoperative reflux (p = 0.02). Second operations included reimplantation in 13 cases, upper pole partial nephrectomy in 7, total nephroureterectomy in 3, bladder neck reconstruction in 3 and lower pole pyeloplasty in 3. The only secondary operations performed for intravesical ureteroceles were reimplantation in 3 cases and upper pole nephrectomy in 1. New onset reflux developed in 14 of 27 patients (52%) postoperatively, including 7 with intravesical and 7 with extravesical ureteroceles. None required a second open operation. CONCLUSIONS: With extended followup the percentage of patients requiring open surgery after endoscopic incision of ureteroceles increased from our original report of 27% to 41% (p = 0.166). Only 18% of cases with an intravesical ureterocele required a subsequent operation compared to 64% with an extravesical ureterocele (p = 0.002). The reduction in size of the obstructed ureter following endoscopic decompression facilitated successful reimplantation. Endoscopic puncture permits definitive treatment in the majority of children by at most a single incision, open operation at the bladder level.

Adolescent↗
PubMed2000

Pediatric reconstructive surgery.

The field of reconstructive pediatric urologic surgery is constantly changing. Recent changes in pediatric urologic reconstructive surgery are discussed in the present review. Surgical techniques for treating patients with hypospadias, exstrophy, incontinence, and ambiguous or variant genitalia are also discussed.

Child↗
PubMed2000

Idiopathic congenital dysmorphic megascrotum.

An enlarged scrotum in the pediatric population constitutes a relatively frequent physical finding requiring evaluation. Most cases of scrotomegaly have a clearly identifiable etiology. We present a patient with an idiopathic congenital dysmorphic megascrotum.

Child, Preschool↗
PubMed2000

The role of renal salvage procedures for bilateral Wilms tumor: a 15-year review.

PURPOSE: We reviewed our experience with renal salvage procedures in patients with bilateral Wilms tumor to determine the clinical outcome. MATERIALS AND METHODS: From 1982 to 1997, 23 children with bilateral Wilms tumor were treated with partial nephrectomy at our institution, including 7 who were also treated with brachytherapy. Medical history, use and response to chemotherapy and brachytherapy, operative records, renal function, pathological results, survival, and techniques for partial and repeat nephrectomy and brachytherapy were reviewed. RESULTS: We treated 8 boys and 15 girls, of whom 21 who presented with synchronous bilateral Wilms tumor underwent primary chemotherapy followed by secondary partial nephrectomy. A total of 44 partial nephrectomies were performed and brachytherapy was done in 7 patients. Ten children have normal renal function and no disease, 10 are dead and 2 have metastatic disease. Anaplasia was the most significant factor associated with an unfavorable outcome (p = 0.003). Of the patients who were cured 60% had a positive response to initial chemotherapy compared with only 25% who had an unfavorable outcome (p = 0.09). No significant differences were noted with respect to gender, age at presentation, highest local tumor stage at presentation or initial nephrectomy. No patient treated with brachytherapy had local recurrence. CONCLUSIONS: Preoperative chemotherapy followed by nephron sparing surgery is indicated in patients with bilateral Wilms tumor, while in those with diffuse anaplasia nephron sparing surgery is contraindicated. Brachytherapy should be considered for treating local disease involving chemoresistant tumors.

Brachytherapy↗
PubMed2000

The outcome of stopping prophylactic antibiotics in older children with vesicoureteral reflux.

PURPOSE: Accepted management of vesicoureteral reflux includes surgical correction or prophylactic antibiotics with the hope for resolution as the child grows. The physician must consider surgery when reflux does not resolve despite uneventful years on prophylactic antibiotics. An alternative is cessation of the antibiotics. We report on the outcome of children taken off antibiotics with persistent reflux. MATERIALS AND METHODS: During a 14-year period 51 children with documented reflux were taken off antibiotic prophylaxis. Selection criteria included children who were old enough to verbalize the symptoms of a urinary tract infection, and had normal voiding patterns, a minor history of infections and minimal or no renal scarring. Routine followup included nuclear cystography and renal sonography. RESULTS: A total of 40 girls and 11 boys maintained on antibiotics for a mean of 4.8 years were taken off prophylaxis and followed for an average of 3.7 years. Mean patient age when prophylactic antibiotics were stopped was 8.6 years. Reflux resolved in 10 children (19.6%). A urinary tract infection developed in 5 girls and 1 boy (11.8%) (mean age 11) an average of 2.3 years (range 4 months to 9.4 years) after antibiotic discontinuation. One child had symptoms consistent with cystitis and 5 had febrile urinary tract infections. All were treated with oral antibiotics and 5 had subsequent operations. No new renal scars developed. CONCLUSIONS: The majority of children did well following cessation of antibiotic prophylaxis despite persistent vesicoureteral reflux. Cessation of antibiotic prophylaxis is a reasonable option in a highly select patient population with reflux.

Adolescent↗
PubMed2000

Testicular volume does not predict germ cell count in patients with cryptorchidism.

PURPOSE: A germ cell count of less than 0.2 germ cell per tubule on the prepubertal biopsy of cryptorchid testes predicts abnormal spermiograms and decreased fertility in adulthood, and may be used to select patients for post-orchiopexy hormonal therapy. Testicular volume directly correlates with testicular function and spermiogenesis. We determined whether testicular volume would predict the total germ cell count accurately enough to replace testicular biopsy in the modern management of cryptorchidism. MATERIALS AND METHODS: At our hospital 723 patients younger than 9 years with cryptorchidism (unilateral in 619 and bilateral in 104) underwent orchiopexy and bilateral testicular biopsies. These patients had not undergone groin surgery or hormonal therapy previously and had at least 50 tubules in each testicular biopsy. Testicular volume and position, patient age and germ cell counts were analyzed. The generalized estimating equation was used to determine whether a correlation existed between testicular volume and germ cell count. RESULTS: The generalized estimating equation demonstrated a direct correlation between testicular volume and germ cell count. However, germ cell counts predicted from testicular volume varied widely within the 95% confidence intervals. Testes with less than 0.2 germ cell per tubule cannot be reliably distinguished from those with greater than 0.2 germ cell per tubule. CONCLUSIONS: Testicular volume does not accurately predict the germ cell count in patients with undescended testes, cannot be used to select patients for post-orchiopexy hormonal therapy and cannot replace testicular biopsy in the modern management of cryptorchidism.

Child↗
PubMed2000

The anatomical approach to inguinal orchiopexy.

PURPOSE: Achieving a scrotally positioned testis with no iatrogenic atrophy is the primary goal of the surgical treatment of cryptorchidism. The success rate is associated with preoperative testicular position and the technique used. Our success rate with inguinal orchiopexy for abdominal testis is higher than those previously published and may be due to our anatomical approach to retroperitoneal dissection. We review the relevant anatomy and discuss the surgical technique of inguinal orchiopexy. MATERIALS AND METHODS: We researched and reviewed the relevant technical and anatomical literature on inguinal orchiopexy, and describe the anatomical approach to orchiopexy in detail. RESULTS: An understanding of the retroperitoneal fascial layers is the key to understanding surgery of the retroperitoneum. Dividing the internal spermatic fascia is required for the surgeon to separate the processus vaginalis from the vas and vessels. CONCLUSIONS: The average age of children undergoing cryptorchid surgery has decreased dramatically during the last 40 years. In such young patients extensive mobilization of the vas and vessels may be accomplished through a relatively small incision. We believe that our success rate with inguinal orchiopexy for abdominal testis is associated with our anatomical approach to retroperitoneal dissection.

Cryptorchidism↗
PubMed1999

Synthesis and antimicrobial activity of 4H-4-oxoquinolizine derivatives: consequences of structural modification at the C-8 position.

The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MRSA. Preliminary studies indicated that oxoquinolizines possess distinct activity and toxicity profiles as compared with their parent quinolones. In order to develop a potent antibacterial agent with the desired spectrum of activity, good tolerability, and balanced pharmacokinetic profile, we synthesized and evaluated a series of oxoquinolizines with various substituents at the C-8 position. Most compounds tested in this study demonstrated better activity against Gram-positive bacteria than ciprofloxacin and exhibited good susceptibility against ciprofloxacin- and methicillin-resistant S. aureus. While maintaining potent in vitro activity, several compounds showed improved in vivo efficacy over ABT-719 as indicated by the mouse protection test. As an example, the oral ED(50) values for the cis-3-amino-4-methylpiperidine analogue 3ss against S. aureus NCTC 10649M, S. pneumoniae ATCC 6303, and E. coli JUHL were 0. 8, 2.0, and 1.4 mg/kg, compared to 3.0, 10.0, and 8.3 mg/kg for ABT-719. The current study revealed that the steric and electronic environment, conformation, and absolute stereochemistry of the C-8 group are very important to the antibacterial profiles. Structural modifications of the C-8 group provide a useful means to improve the antibacterial activities, physicochemical properties, and pharmacokinetic profiles. Manipulation of the C-8 group also allows us to generate analogues with the desired spectrum of activity, such as analogues that are selective against respiratory pathogens.

Animals↗
PubMed1999

Telomerase repressor sequences on chromosome 3 and induction of permanent growth arrest in human breast cancer cells.

BACKGROUND: Activation of the enzyme telomerase, which has been associated with cellular immortality, may constitute a key step in the development of human cancer. Telomerase is repressed in most normal human somatic cells. This study was conducted, using a genetic complementation approach, with the aim of identifying and mapping the genes responsible for repressing telomerase and, simultaneously, to establish the effect of experimentally induced telomerase repression on human tumor cell growth. METHODS: Individual human chromosomes isolated from normal diploid cells and tagged with bacterial antibiotic resistance genes (for later selection) were introduced into cells of the human breast carcinoma cell line 21NT by means of microcell transfer. Selected hybrid clones were screened for telomerase activity by use of the polymerase chain reaction-based telomere repeat amplification protocol (TRAP) assay, and the proliferative fate of the hybrid clones was determined. Regions of the introduced chromosomes associated with telomerase repression were mapped using segregant hybrids and a deletion analysis that employed microsatellite DNA markers. RESULTS: Strong repression of telomerase was observed following transfer of human chromosome 3 into 21NT cells but not after transfer of chromosomes 8, 12, or 20. The vast majority of hybrid clones with repressed telomerase entered permanent growth arrest after 10-18 population doublings. Deletion analysis of nonrepressed segregant monochromosome 3 hybrids indicated two regions on the short arm of chromosome 3 (3p21.3-p22 and 3p12-21.1) where telomerase regulator genes may be located. CONCLUSIONS: Telomerase in human breast cancer cells is efficiently repressed by a gene or genes on normal human chromosome 3p, and this repression is associated with permanent growth arrest of the tumor cells.

Adult↗
PubMed1999

False-positive pregnancy test associated with gonadoblastoma.

Gonadoblastomas are known to be hormonally active tumors that occur in streak or dysgenetic gonads of patients with intersex abnormalities. Several reports document their ability to produce beta-human chorionic gonadotropin (HCG), but none have documented an elevated peripheral serum beta-HCG. We report on the case of a patient with pure gonadal dysgenesis with XY karyotype who was found to have an elevated peripheral serum beta-HCG after a positive pregnancy test. Knowledge of gonadoblastoma's potential to elevate serum beta-HCG levels may prevent unnecessary searches for other causes.

Adolescent↗
PubMed1999

BCL10 is rarely mutated in human prostate carcinoma, small-cell lung cancer, head and neck tumours, renal carcinoma and sarcomas. MPT Collaborators, St George's Hospital Collaborators.

We have used single-strand conformation polymorphism (SSCP) analysis to screen for mutations in the BCL10 gene in 81 primary prostate carcinomas, 20 squamous cell cancers of the head and neck, 15 small-cell lung cancer cell lines, 24 renal carcinoma cell lines and 13 sarcoma cell lines. We failed to find evidence of somatically acquired mutations of the BCL10 gene suggesting that BCL10 does not play a major role in the development of these malignancies.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus.

The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Here we have investigated the functional domains of the proteins. The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species, and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences. Deletion of the SNH domain results in a more active transcriptional activator, suggesting that this domain acts as an inhibitor of the activation domain. The C-terminal SSX domain present in SYT-SSX translocation protein contributes a transcriptional repressor domain to the protein. Thus, the fusion protein has transcriptional activating and repressing domains. We demonstrate that the human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with SYT and SYT-SSX proteins in vitro. This interaction may provide an explanation of how the SYT protein activates gene transcription.

Amino Acid Sequence↗
PubMed1999

Comparison of calcaneal ultrasound and DXA in young women.

PURPOSE: The purpose of the study was to assess quantitative ultrasound (QUS) parameters in collegiate female gymnasts, a population whose training incorporates high-impact loading, which is particularly osteogenic, and to determine the discriminative capacity of this relatively new radiation-free technique compared with bone densitometry in a young healthy population. METHODS: We studied 19 collegiate gymnasts and 23 healthy controls undergoing regular weight-bearing activity, matched for age (gymnasts 19.2 +/- 1.2, controls 19.9 +/- 1.6 yr) and body weight (gymnasts 56.7 +/- 3.7, controls 57.7 +/- 7.8 kg). QUS parameters of the calcaneus (broadband ultrasound attenuation (BUA), bone velocity (BV), and speed of sound (SOS)) were measured by a Walker Sonix UBA 575+. Bone mineral density (BMD; g x cm(-2)) of the lumbar spine, hip (femoral neck, trochanter, Ward's triangle) and whole body was assessed by dual energy x-ray absorptiometry (DXA, Hologic QDR 1000/W). Data analysis included unpaired two-tailed Student's t-tests, analysis of variance, Pearson product-moment, and Spearman rank-order correlations. RESULTS: Regional and whole body BMD of gymnasts was greater than controls (P < 0.001), with the difference being 7-28%. Average QUS parameters of the right and left calcaneus were also higher (P < 0.001) in the gymnasts. BUA, BV, and SOS were significantly (P < 0.001) correlated to each bone site with r = 0.54-0.79. Analysis of receiver operating characteristic (ROC) curves indicated no significant difference in sensitivity and specificity for QUS and DXA measures. CONCLUSIONS: These results indicate that QUS parameters of the calcaneus are higher in young women gymnasts compared to individuals who undergo regular weight-bearing activity and that QUS parameters are able to discriminate between these two groups in a similar manner as does regional and whole body BMD.

Absorptiometry, Photon↗
PubMed1999

Photogenotoxicity of fluoroquinolones in Chinese hamster V79 cells: dependency on active topoisomerase II.

The Chinese hamster V79 lung cell in vitro micronucleus assay was adapted to detect and quantify phototoxicity and photogenotoxicity of fluoroquinolones. Using this assay, the quinolones were ranked in terms of decreasing phototoxicity: clinafloxacin >> lomefloxacin, sparfloxacin >> trovafloxacin, nalidixic acid, ofloxacin, ciprofloxacin > enoxacin, norfloxacin. This rank order agrees well with published studies utilizing various other phototoxicity models and establishes this approach as a fast and sensitive way to characterize the phototoxic potential of quinolones. Nearly complete inhibition of phototoxicity was observed if the cells were pretreated for as little as 1 min with 10-20 mM sodium azide prior to the addition of quinolone. An identical azide effect was seen in unirradiated quinolone- and etoposide-treated cells. These findings are consistent with a model in which sodium azide renders DNA topoisomerase II catalytically inactive. In this state, topoisomerase II cannot initiate DNA strand cleavage and the DNA/topoisomerase complex becomes insensitive to quinolones and other topoisomerase II inhibitors. The fact that azide reduces both UV-dependent and UV-independent toxicity and clastogenicity strongly suggests a common mechanism of toxicity dependent on the formation of topoisomerase-induced DNA double-strand breaks.

Animals↗
PubMed1999

Lack of association of anabolic hormone status and muscle strength with regional and whole body bone mineral density in healthy men aged 60-79 years.

This study investigated the capacity of muscle strength and anabolic hormone status to predict regional and whole body bone mineral density (BMD) in older men. Fifty-two healthy men aged 60-79 years served as subjects. BMD of the lumbar spine, proximal femur, upper and lower limbs, and whole body was assessed by dual X-ray absorptiometry. Dynamic muscle strength for several upper and lower body muscle groups was determined by the one-repetition maximum and isometric grip strength by dynamometry. Anabolic hormone status was assessed by the ratio of testosterone (T) to sex hormone binding globulin (SHBG), given as the free androgen index (FAI), and the ratio of insulin-like growth factor I (IGF-I) to IGF binding protein-3 (IGFBP-3). Age was associated with declines in dynamic strength and the log FAI. In stepwise regression analysis, only body mass was an independent predictor of whole body and upper limb BMD (R2 = 0.13), and hip adductor strength predicted the Ward's triangle (R2 = 0.14). For lumbar spine BMD, triceps extensor strength was significantly correlated (r = 0.36, p < 0.01), while no strength or hormonal variable was associated with the femoral neck, trochanter, or lower limb. The lack of association between muscle strength and BMD was generally unaltered after controlling for hormone status and body mass. There was no difference in BMD when analyzed by tertiles of log FAI or IGF-I/IGFBP-3 or by tertiles of muscle strength. These results suggest that in healthy community-dwelling men in the seventh and eighth decade, muscle strength and hormonal status are not significant contributors to regional or whole body BMD.

Aged↗