Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency.

Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our previous findings of a genetic variation in the development of TD symptoms, we extended our studies to mice.

Creation of a model of bladder exstrophy in the fetal lamb.

Purpose: To our knowledge we describe the first reproducible large animal model to mimic the congenital birth defect of classic bladder exstrophy.

Materials And Methods: Eight male and 15 female fetal sheep underwent in utero surgical creation of classic bladder exstrophy. The fetus was then replaced within the amniotic sac and allowed to come to term.

Reappraisal of the role of human chorionic gonadotropin in the diagnosis and treatment of the nonpalpable testis: a 10-year experience.

Purpose: We retrospectively evaluated the ability of human chorionic gonadotropin (HCG) to make the nonpalpable cryptorchid testis become palpable and promote testicular descent.

Materials And Methods: Through surgical bookings we identified 94 patients younger than 11 years who received HCG between 1984 and 1994 for the diagnosis or treatment of a nonpalpable undescended testis. The dose of HCG was 1,500 IU/m.

Current management of bladder exstrophy.

This article describes in detail the modern management of the patient born with classic bladder exstrophy. Also, new techniques of prenatal diagnosis and pelvic fixation to secure the initial or secondary closure are discussed. Last, management of the failed closure and the bladder not suitable for closure are described and outlined.

The outcome of patients with classic bladder exstrophy in adult life.

Purpose: We determined the outcome of 20 older adult bladder exstrophy patients regarding urinary continence, sexual function, fertility and psychosocial integration.

Materials And Methods: A total of 16 men and 4 women completed an anonymous questionnaire and the charts were reviewed for medical history.

Results: Of 9 patients who void spontaneously 6 are dry for 4 hours and 3 for 2 hours.

Nitric oxide synthase and tyrosine hydroxylase are colocalized in nerves supplying the postnatal human male genitourinary organs.

Purpose: The objective of this study was to examine the distribution of nitric oxide synthase (NOS) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) in nerve fibers supplying the human neonatal male genitourinary organs.

Materials And Methods: An indirect double label immunofluorescence technique was employed on specimens obtained from infants and children at postmortem examination.

Results: Many nerve fibers immunoreactive for both NOS and TH were observed in the muscle coat of the vas deferens and the seminal vesicle, within the fibromuscular stroma of the prostate gland and at the bladder neck, and also formed perivascular plexuses in each of these organs.

Ambiguous genitalia in an elderly woman with a mosaic 45,X/46,X,dic(Y)(Q11.2) karyotype.

A 66-year-old woman presented with clitoromegaly since childhood, primary amenorrhea, no breast development, and a large right inguinal hernia. A mosaic karyotype was identified containing a predominant 45,X cell line and a cell line with 46 chromosomes, one X chromosome, and a small dicentric Y chromosome with a breakpoint in band qII.2.

The multiple reoperative bladder exstrophy closure: what affects the potential of the bladder?

Objectives: To define the possible cause of failure and the eventual potential of the bladder in 23 exstrophy patients, who underwent more than two failed prior attempts at closure.

Methods: Twenty-three patients were selected from the exstrophy data base who had two or more prior closures. Eighteen patients had undergone 2 previous closures and 5 patients 3 previous closures for either complete dehiscence or significant prolapse.

A combined vertical and horizontal pelvic osteotomy approach for primary and secondary repair of bladder exstrophy.

Purpose: We describe a new combined horizontal and vertical pelvic osteotomy procedure for bladder exstrophy.

Materials And Methods: A total of 36 patients with the bladder exstrophy complex underwent this procedure during a 3-year period (8 primary and 18 secondary bladder closures, and 6 at bladder neck reconstruction).

Results: There were no instances of dehiscence and only a minor bladder prolapse in 1 patient with cloacal exstrophy.

Alterations of yeast artificial chromosome transgenic sequences in stretched embryonic stem-cell chromatin visualized by fluorescence in situ hybridization.

Transgenic mice have been generated from embryonic stem (ES) cells carrying functional genes cloned within yeast artificial chromosomes (YACs). Information on the integrity and organization of the inserted sequences, including the number of copies and their orientation to each other, is still limited by current methods. We have applied fluorescence in situ hybridization to stretched chromatin preparations from YAC-transfected ES cells to analyze the organization and copy number of the integrated sequences.

Evolution of outcomes with the ileal hydraulic valve continent diversion: reevaluation of the Benchekroun catheterizable stoma.

Initial reports with limited follow-up suggested that the ileal hydraulic valve was a satisfactory approach to continent urinary diversion that was associated with acceptable early complication rates and uniform efficacy in achieving continence. We sought to evaluate the later outcomes of patients with this form of continent urinary diversion. An average extended follow-up of 5 years was available on 11 patients who had undergone ileal hydraulic valve diversion.

Bladder exstrophy from childhood into adult life.

Exstrophy of the bladder is rare and the incidence of bladder exstrophy is calculated to be from 1 per 30,000 to 50,000 live births with male to female ratio ranging from 1.5-5 to 1(1-4). It was found that persistence or overgrowth of the cloacal membrane on the lower anterior abdominal area, prevents normal mesenchymal ingrowth.

Characterization of transgenic mice with an increased content of chromosomal protein HMG-14 in their chromatin.

Chromosomal protein HMG-14 is a ubiquitous nuclear protein that may modulate the chromatin structure of transcriptionally active genes. To gain insights into the cellular function of the HMG-14 protein, we generated two transgenic mouse lines carrying either two or six copies of the human HMG-14 gene. The transgenic mice express human HMG-14 mRNA and protein in all tissues examined at a level reflecting the increased gene dosage, suggesting that the HMG14 transgene contains all the control regions necessary for regulated gene expression.

Prevalence and repair of inguinal hernias in children with bladder exstrophy.

Purpose: We delineated the prevalence, recurrence rates and optimal treatment of inguinal hernia in the exstrophy population.

Materials And Methods: Of 181 children with exstrophy followed at our hospital inguinal hernias developed in 121 (66.8%).

Applications of osteotomy in the cloacal exstrophy patient.

During the last 18 years we treated 22 patients with cloacal exstrophy of whom 13 were referred for further treatment after initial treatment elsewhere. One patient underwent cystectomy with ileal conduit urinary diversion soon after birth and 9 of the remaining 21 underwent initial closure without osteotomy. Of these 9 patients significant complications developed in 8 (89%) after bladder closure, including dehiscence in 6 (1 underwent 2 unsuccessful closures), a vesicocutaneous fistula and postoperative ventral hernia in 1, and bladder prolapse in 1.

Submucosal bladder neck injections of glutaraldehyde cross-linked bovine collagen for the treatment of urinary incontinence in patients with the exstrophy/epispadias complex.

During the last 7 years 19 patients underwent 33 transurethral injections of glutaraldehyde cross-linked bovine collagen into the bladder neck for stress incontinence. Of the 15 patients 14 have classic bladder exstrophy, 3 have complete male epispadias and 2 have cloacal exstrophy. The procedure was performed after a Young-Dees-Leadbetter bladder neck reconstruction in 15 patients and before it in 4.

Reanalysis of dose-response data from the Iraqi methylmercury poisoning episode.

Applying a hockey stick parametric dose-response model to data on late or retarded development in Iraqi children exposed in utero to methylmercury, with mercury (Hg) exposure characterized by the peak Hg concentration in mothers' hair during pregnancy, Cox et al. calculated the "best statistical estimate" of the threshold for health effects as 10 ppm Hg in hair with a 95% range of uncertainty of between 0 and 13.6 ppm.

Considering pharmacokinetic and mechanistic information in cancer risk assessments for environmental contaminants: examples with vinyl chloride and trichloroethylene.

Risk assessments for vinyl chloride (VC) and trichloroethylene (TCE) are presented as examples of approaches for incorporating chemical-specific pharmacokinetic and mechanistic information into a more scientifically plausible cancer risk assessment. For VC, the evidence regarding mode of action includes direct reaction of a metabolite with DNA, resulting in DNA adducts and mistranscription, and cross-species target-tissue correspondence of a rare tumor type. Risk estimates for human exposure to VC predicted with a physiologically-based pharmacokinetic (PBPK) model and the linearized multistage (LMS) model were lower than those currently used in environmental decision-making by a factor of 30 to 50, and were more consistent with human epidemiological data.

The Cantwell-Ransley epispadias repair in exstrophy and epispadias: lessons learned.

Objectives: We evaluated our experience with the Cantwell-Ransley epispadias repair to determine the lessons that have been learned with the increased experience and follow-up.

Methods: A total of 75 boys (60 with bladder exstrophy and 15 with complete epispadias) underwent a Cantwell-Ransley epispadias repair at our institute in the last 6 years. Primary repair was performed in 58 boys (45 with exstrophy and 13 with epispadias), and secondary repair was performed after prior failed closure in 17 boys (12 at the secondary exstrophy closure, 3 with exstrophy, and 2 with complete epispadias).

Criteria for the prenatal diagnosis of classic bladder exstrophy.

Objective: To define ultrasonographic criteria for the prenatal diagnosis of classic bladder exstrophy.

Methods: Forty-three prenatal ultrasound scans were studied from 25 pregnancies in which live delivery of an infant with classic bladder exstrophy occurred. The diagnosis of bladder exstrophy could be made retrospectively in 29 prenatal studies from 17 pregnancies.

Initial management of the patient with newly diagnosed diabetes.

A family physician is often the one who makes an initial diagnosis of diabetes. The physician must consider the impact of this diagnosis on both the patient and the patient's family members. Outpatient management is less costly and less traumatic for the patient than inpatient care.

YAC transgenics and the study of genetics and human disease.

Advances in yeast artificial chromosome (YAC) technologies over the past decade have enabled the precise identification and manipulation of large genomic regions (>100 kb) of DNA. Introduction of YACs into the mouse germline has now been accomplished through transfection of mouse embryonic stem cells as well as through pronuclear microinjection, allowing the efficient transfer defined genomic loci into mice. YAC transgenics will have a profound impact on the development of transgenic mice as bioreactors and as models of human disease, and on the functional analysis of higher order genomic structure.

Early identification and management of hearing impairment.

Early detection and treatment of hearing loss can prevent a lifetime of difficulties. Severe sensorineural hearing loss is present in approximately one in 1,000 newborns. Many newborns have mild to moderate hearing loss, either conductive or sensorineural, that interferes with normal functioning.