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Biomedical subjects

David A Bloom

Publications and source records attributed to David A Bloom.

At least 19 recordsLinked to original sources

Edward Loughborough Keyes: an early twentieth century leader in urology.

PURPOSE: Edward Loughborough Keyes was a renowned urologist, decorated war hero, prolific writer and beloved professor. Having served as president of the American Association of Genitourinary Surgeons, the American Urological Association, the International Urological Society and the Clinical Urological Association, Keyes in large part steered the course of urology during the early twentieth century. MATERIALS AND METHODS: We reviewed letters, original publications and historical records pertaining to Doctor Keyes found in the New York Hospital archives, the American Urological Association historical record, the medical literature and the popular press. RESULTS: Edward Loughborough Keyes, Jr. received his M.D. from Columbia in 1895, and went on to hold academic positions in urology at Georgetown, the New York Polyclinic Medical School, St. Vincent's Hospital, Memorial Hospital, New York University and at the Cornell University Medical College, where he spent most of his career. He authored the premier urology textbook of his day, Urology, and published prolifically on a myriad of urological conditions. Doctor Keyes served in World War I as consultant in urology to General John J. Pershing, commander of the American Expeditionary Force. During the war he and Hugh Hampton Young led modern history's first public campaign against sexually transmitted disease, and in America he was one of the leaders of the American social hygiene movement from which contemporary sexual education evolved. He spoke Spanish and French fluently, wrote poetry and prose prolifically, and was beloved for his good humor. He died at the age of 75 in New York. CONCLUSIONS: Edward Loughborough Keyes is remembered as one of the great urologists of the early twentieth century.

History, 19th Century↗

MR angiography in the evaluation of a renovascular cause of neonatal hypertension.

Neonatal hypertension occurs in 2% of all infants and it is caused by renovascular abnormalities in 70% of these infants. The gold standard for diagnosing renovascular disease is conventional renal angiography. However, in neonates the procedure is not commonly used because of its invasive and technically challenging nature. MRI and MR angiography (MRA) are less invasive yet reliable means of detecting renovascular disease in adults. There is minimal literature on the use of MRI/MRA in neonatal hypertension. We report a neonate with hypertension secondary to a renovascular abnormality in which MRI/MRA was helpful in uncovering segmental renal artery stenosis. The infant underwent partial nephrectomy with subsequent resolution of his hypertension. Further studies are needed to validate the use of MRI/MRA in the evaluation of neonatal hypertension.

Gadolinium↗

Calciphylaxis in pediatric end-stage renal disease.

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patient's clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.

Adolescent↗

Nuclear import and export signals in control of Nrf2.

Nrf2 binds to the antioxidant response element and regulates expression and antioxidant induction of a battery of chemopreventive genes. In this study, we have identified nuclear import and export signals of Nrf2 and show that the nuclear import and export of Nrf2 is regulated by antioxidants. We demonstrate that Nrf2 contains a bipartite nuclear localization signal (NLS) and a leucine-rich nuclear export signal, which regulate Nrf2 shuttling in and out of the nucleus. Immunofluorescence and immunoblot analysis revealed that Nrf2 accumulates in the nucleus within 15 min of antioxidant treatment and is exported out of nucleus by 8 h after treatment. Nrf2 mutant lacking the NLS failed to enter the nucleus and displayed diminished expression and induction of the downstream NAD(P)H:quinone oxidoreductase 1 gene. The Nrf2 NLS sequence, when fused to green fluorescence protein, resulted in the nuclear accumulation of green fluorescence protein, indicating that this signal sequence was sufficient to direct nuclear localization of Nrf2. A nuclear export signal (NES) was characterized in the C terminus of Nrf2, the deletion of which caused Nrf2 to accumulate predominantly in the nucleus. The Nrf2 NES was sensitive to leptomycin B and could function as an independent export signal when fused to a heterologous protein. Further studies demonstrate that NES-mediated nuclear export of Nrf2 is required for degradation of Nrf2 in the cytosol. These results led to the conclusion that Nrf2 localization between cytosol and nucleus is controlled by both nuclear import and export of Nrf2, and the overall distribution of Nrf2 is probably the result from a balance between these two processes. Antioxidants change this balance in favor of nuclear accumulation of Nrf2, leading to activation of chemopreventive proteins. Once this is achieved, Nrf2 exits the nucleus for binding to INrf2 and degradation.

Active Transport, Cell Nucleus↗

Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants.

The antioxidant response element (ARE) and Nrf2 are known to regulate the expression and coordinated induction of genes encoding detoxifying enzymes including NAD(P)H:quinone oxidoreductase1 (NQO1) in response to antioxidants. In this report, we demonstrate that overexpression of the transcription factor Bach1 in Hep-G2 cells negatively regulated NQO1 gene expression and induction in response to antioxidant t-BHQ. Bandshift and supershift assays revealed that Bach1 binds to the ARE as a heterodimer with small Maf proteins but not as a homodimer or heterodimer with Nrf2. The transfection and ChIP assays revealed that Bach1 and Nrf2 competed with each other to regulate ARE-mediated gene expression. Heme, a negative regulator of Bach1 relieved the Bach1 repression of NQO1 gene expression in transfected cells. The transcription of Bach1 and Nrf2 did not change in response to t-BHQ. Immunofluorescence assays and Western blot analysis revealed that both Bach1 and Nrf2 localized in the cytoplasm and nucleus of the untreated cells. The treatment of cells with t-BHQ resulted in the nuclear accumulation of both Bach1 and Nrf2. Interestingly, the t-BHQ-induced nuclear accumulation of Bach1 was significantly delayed over that of Nrf2. These results led to the conclusion that a balance of Nrf2 versus Bach1 inside the nucleus influences up- or down-regulation of ARE-mediated gene expression. The results further suggest that antioxidant-induced delayed accumulation of Bach1 contributes to the down-regulation of ARE-regulated genes, presumably to reduce the antioxidant enzymes to normal levels.

Antioxidants↗

Bladder exstrophy in the newborn: a snapshot of contemporary practice patterns.

OBJECTIVES: To use a large nationwide database to investigate and describe practice patterns in the contemporary management of bladder exstrophy. METHODS: The Healthcare Cost and Utilization Project Nationwide Inpatient Sample (1988 to 2000) was queried to identify infants with bladder exstrophy hospitalized during the first week after birth. Admission and disposition patterns, resource utilization and length of stay, surgical repair trends, and factors associated with in-hospital death were analyzed. RESULTS: We identified 426 hospital admissions of newborns with exstrophy. Most patients (75%) were transferred in from, or out to, other facilities; this was a fundamental feature of early exstrophy care. Racial differences were evident, with Hispanics less likely to be transferred (19% versus 60%, P = 0.001). Among newborns who were not transferred, many (46%) were discharged without bladder surgery. Surgical repair was usually done in a hospital other than the birth hospital; the mean hospital charges for surgery were 75,742 dollars. Of the 5 patients who died after repair, all had undergone surgery at "low-volume" hospitals. The length of stay did not change significantly during the study period, helping to keep resource utilization high in this population. CONCLUSIONS: The results of this study provide a "snapshot" of bladder exstrophy practice patterns during the newborn period between 1988 and 2000. Additional research should investigate whether newborns with exstrophy are receiving optimal care, including appropriate timing of surgery, equitable transfers to tertiary centers, and reconstruction at centers with adequate volume and experience.

Bladder Exstrophy↗

Patient-reported sexual function after oral mucosa graft urethroplasty for hypospadias.

OBJECTIVES: To evaluate sexual function after oral mucosa graft urethroplasty (OMGU) for hypospadias. Few long-term patient-reported data are available regarding sexual function after surgery for hypospadias. METHODS: We identified patients aged 18 years or older at the time of this survey who had undergone OMGU for hypospadias between 1992 and 2003. We evaluated sexual function and satisfaction using the 15-item International Index of Erectile Function (IIEF-15). RESULTS: Of the 16 adult patients, we located 14, of whom 11 (79%) participated. Previous hypospadias repair had failed in all 11 before OMGU. The median age at OMGU was 17.5 years. The median follow-up time was 4.7 years. Of the 10 sexually active patients, the mean score on the IIEF-15 was 64.6 +/- 11.9 (maximal possible score 75). Erectile function was excellent, with all 10 able to achieve an erection most or all of the time (mean erection domain score 26.8 +/- 6.1). All 10 experienced sensation of orgasm most or all the time, although 1 never ejaculated and 2 ejaculated rarely (mean orgasm domain score 8.9 +/- 1.8). All 10 reported that they were moderately (n = 6) or very (n = 4) satisfied with their overall sex life (mean satisfaction domain score 8.3 +/- 1.9). Neither occurrence of post-OMGU complications nor satisfaction with penile appearance was significantly associated with the IIEF-15 scores or overall sexual satisfaction. CONCLUSIONS: Long-term sexual function and satisfaction was excellent in these patients after OMGU for hypospadias. Adolescent boys and men with failed hypospadias repairs, as well as parents of boys with hypospadias, can be counseled that most patients who undergo OMGU are likely to have satisfactory sexual function as adults.

Adolescent↗

A syndrome of hypoplastic sinuses, hydrocephalus, bronchiectasis, and hypogammaglobulinemia with functional antibody deficiency in twin girls.

BACKGROUND: A variety of syndromes are known to be associated with immune deficiency, some as a major part of the syndrome and some as an occasional finding. OBJECTIVES: To report a newly defined syndrome of hydrocephalus, hypoplastic sinuses, cartilaginous webbing of the bronchi, bronchiectasis, and hypogammaglobulinemia with functional antibody deficiency in identical twin girls. METHODS: Spirometry, radiography, computed tomography (CT), bronchoscopy, and laboratory tests were performed for diagnosis. RESULTS: A girl (twin A) was evaluated at the age of 7 years for chronic cough and wheeze that worsened with exercise. Hydrocephalus had been diagnosed a year before evaluation. She was treated for cough variant asthma and was lost to follow-up until the age of 10 years. The cough had worsened progressively, and dyspnea was now apparent. Spirometry was consistent with reversible airway obstruction. A chest radiograph was suggestive of bronchiectasis. A chest CT scan showed bilateral upper lobe bronchiectasis. Hypogammaglobulinemia and functional antibody deficiency were noted. A CT scan of the sinuses revealed aplasia or severe hypoplasia of all the paranasal sinuses. Bronchoscopy revealed a grossly abnormal bronchial structure and atrophic-appearing bronchial mucosa. Twin B also had a history of hydrocephalus. Although she had no respiratory symptoms, chest CT revealed bronchiectasis, and she had obstruction on spirometry. Laboratory analysis revealed hypogammaglobulinemia and functional antibody deficiency. She became symptomatic 2 years after twin A. CONCLUSIONS: This is a newly reported syndrome of hydrocephalus, absent sinuses, abnormalities of the bronchi, and functional antibody deficiency, which initially presented as cough and wheeze.

Agammaglobulinemia↗

Thomas Annandale and the first report of successful orchiopexy.

PURPOSE: We investigate the surgeon and factors behind the first report of successful orchiopexy. MATERIALS AND METHODS: We reviewed the first reports of orchiopexy, and the work and writings concerning Thomas Annandale and the time in which he practiced. RESULTS: Annandale was a surgeon in Edinburgh, Scotland, in the late 19th century. In 1877 he successfully brought down an ectopic testicle in a 3-year-old boy. This first reported successful orchiopexy was due in large part to Lister's antiseptic technique. CONCLUSIONS: Annandale performed the first successful orchiopexy by integrating the surgical and antiseptic ideas of his predecessors and contemporaries.

Cryptorchidism↗

Long-term patient reported outcome and satisfaction after oral mucosa graft urethroplasty for hypospadias.

PURPOSE: There is a paucity of long-term patient reported outcome data on surgery for hypospadias. We sought to evaluate genitourinary function and satisfaction after oral mucosa graft urethroplasty (OMGU) for hypospadias. MATERIALS AND METHODS: We identified 65 patients who had undergone OMGU at our institution between 1992 and 2003, and surveyed these patients to evaluate oral health, urinary function and satisfaction with outcomes. RESULTS: We located 51 patients who had undergone OMGU, of whom 43 (84%) agreed to participate in the study. Median followup was 6.9 years. Mean study age was 15.1 years. Of the patients 47% had severe hypospadias with failed previous repair and 42% had severe hypospadias with previous first stage surgery. Oral complaints were rare and primarily cosmetic. No patient whose oral harvest was limited to the cheek (vs lip) had cosmetic complaints. Urinary spray and stream deviation were reported by 11 patients (26%) and 12 patients (28%), respectively. American Urological Association symptom scores were generally low (mean 5.6 +/- 6.0, range 0 to 21) but 7 patients (16%) had moderate symptoms and 2 (5%) had severe symptoms. Of the patients 60% were mostly satisfied or better with urinary function. Although satisfaction with penile appearance varied (51% of patients were satisfied), most patients (84%) were satisfied with the overall hypospadias care. Urinary symptom scores were significantly worse among patients who had post-OMGU complications (p = 0.004). Of these patients 38% had moderate or severe urinary symptoms, while 95% of patients without complications had mild symptoms (p = 0.01). CONCLUSIONS: Many patients report good long-term outcomes of OMGU, although a subset of patients has significant urinary and cosmetic complaints that are more prevalent in association with surgical complications.

Adolescent↗

The increasing incidence of congenital penile anomalies in the United States.

PURPOSE: Epidemiologic studies have suggested that the incidence of congenital penile anomalies (CPA), particularly hypospadias, is increasing. This phenomenon has significant biological and socioeconomic implications. We sought further confirmation of the reported trends using a large national database. MATERIALS AND METHODS: The Nationwide Inpatient Sample is a 20% sample of United States hospitals containing data on 5 to 7 million hospital inpatient stays per year. We identified male newborns, used ICD-9 codes to identify newborns with CPA, determined nationally weighted incidence over time and performed multivariate analyses to identify factors associated with CPA. RESULTS: Of the 4.84 million male newborns in the Nationwide Inpatient Sample we identified 37,577 with CPA (weighted incidence rate 7.8/1000 newborns). The weighted incidence increased from 7.0/1000 newborns in 1988 to 1991 to 8.3/1000 in 1997 to 2000 (p <0.0001). The most common diagnosis was hypospadias (68.3%), followed by chordee (8.6%) and hypospadias plus chordee (5%). Unspecified genital or penile anomalies were reported for 14% of the cases. The highest incidence of CPA was in white newborns (9.2/1000), followed by black newborns (7.5/1000), Asians (5.0/1000) and Hispanics (4.7/1000) (p <0.0001). Socioeconomic status (SES) was strongly associated with CPA, with CPA odds 19% higher for the highest SES category versus the lowest (OR 1.18, 95% CI 1.16-1.20). Increasing incidence of CPA over time was observed even after adjusting for race/ethnicity, geographic region, insurance status and SES. CONCLUSIONS: These nationally representative, weighted analyses reveal a significant increase in the incidence of CPA, with striking variation by race, region and SES. Further research into potential causes, as well as the observed disparities in incidence, is needed.

Chi-Square Distribution↗

Defining the role of magnetic resonance imaging in unifocal bone lesions of langerhans cell histiocytosis.

Localized Langerhans cell histiocytosis (LCH) of bone often presents as a diagnostic challenge. Magnetic resonance imaging (MRI) is frequently used to better delineate most solitary bony lesions. The authors present two cases that illustrate and better define the role of MRI in the evaluation of solitary bone lesions of LCH. In a 3-year-old boy with left-sided hip pain, MRI showed a focal lesion involving the proximal left femur with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. A tumor was suspected because of the overall imaging characteristics and increased uptake on three-phase nuclear scintigraphy. In a 6-year-old boy with right thigh pain, MRI showed a fluid-containing lesion in the mid-diaphysis of the right femur, suggestive of chronic osteomyelitis and Brodie abscess. MRI was instrumental in showing the extent of the lesions in both cases; however, the final diagnosis of LCH was achieved only with histopathologic confirmation, illustrating the limited diagnostic power of this imaging tool.

Bone Diseases↗