Reconstruction of the symphysis pubis to repair a complex midline hernia in the setting of congenital bladder exstrophy.

PURPOSE: A 40-year-old man with congenital midline defect and wide pubic symphysis diastasis secondary to bladder exstrophy presented with a massive incisional hernia resulting from complications of multiple prior abdominal repairs. Using a multi-disciplinary team of general, plastic, and urologic surgeons, we performed a complex hernia repair including creation of a pubic symphysis with rib graft for inferior fixation of mesh. METHODS: The skin graft overlying the peritoneum was excised, and the posterior rectus sheath mobilized, then re-approximated. The previously augmented bladder and urethra were mobilized into the pelvis, after which a rib graft was constructed from the 7th rib and used to create a symphysis pubis using a mortise joint. This rib graft was used to fix the inferior portion of a 20 × 25 cm porcine xenograft mesh in a retro-rectus position. With the defect closed, prior skin scars were excised and the wound closed over multiple drains. RESULTS: The patient tolerated the procedure well. His post-operative course was complicated by a vesico-cutaneous fistula and associated urinary tract and wound infections. This resolved by drainage with a urethral catheter and bilateral percutaneous nephrostomies. The patient has subsequently healed well with an intact hernia repair. The increased intra-abdominal pressure from his intact abdominal wall has been associated with increased stress urinary incontinence. CONCLUSIONS: Although a difficult operation prone to serious complications, reconstruction of the symphysis pubis is an effective means for creating an inferior border to affix mesh in complex hernia repairs associated with bladder exstrophy.

Chelation therapy in beta-thalassemia: an optimistic update.

Iron chelation therapy with desferrioxamine (DFO) has dramatically improved the outlook in beta-thalassemia. Parenteral DFO reduces tissue iron stores, prevents iron-induced organ damage, and reduces morbidity and mortality, with little serious toxicity. However, the burden of prolonged subcutaneous portable pump infusions, high cost, and patient noncompliance have prompted the development of new methods of administration and new formulations of DFO as well as oral iron chelators. Deferiprone (L1), the only oral iron chelator studied in large long-term clinical trials, is less effective and more toxic than DFO and may not adequately control iron overload; however, compliance and quality of life are improved. Combinations of two iron chelators (such as parenteral DFO plus oral L1, or 2,3-DHB; or oral L1 plus HBED) have been shown to produce additive and synergistic effects, explained by the shuttle hypothesis. Iron bound to a "shuttle"--an oral agent that mobilizes tissue iron--is exchanged in the bloodstream with a "sink"--such as parenteral DFO--and excreted via the kidneys, while the shuttle is reutilized. Combination therapy may produce enhanced iron excretion, target specific iron compartments, minimize side effects, increase treatment options, improve compliance, and facilitate individualization of therapy. Better understanding of the kinetics of iron metabolism, iron overload, and chelation should improve therapeutic strategies.

Current management of prepubertal yolk sac tumors of the testis.

Over the last 3 decades, the management of pediatric yolk sac tumors of the testis has changed significantly. These changes reflect improvement in the treatment of testicular tumors in adults and children, such as the advent of platinum-based chemotherapy regimens. They also reflect increased understanding of the biology and natural history of prepubertal yolk sac tumors of the testis as a unique disease entity.

Complete primary repair of exstrophy. Surgical technique.

The single-stage reconstructive approach to exstrophy evolved out of changes in the management of exstrophy. The success of Jeffs and others that functionally reconstructed the bladder of patients with exstrophy demonstrated that the approach was feasible and acceptable. Increased understanding of the anatomic pathology associated with exstrophy and epispadias resulted in the development of complete penile disassembly for epispadias and the extension of this technique to exstrophy as the complete primary repair technique described herein. The results using this technique are encouraging, leading to the recommendation for the procedure by other surgeons committed to the care of patients with exstrophy.

Long-term followup of the hematuria-dysuria syndrome.

PURPOSE: The hematuria-dysuria syndrome is the most common reported complication of gastrocystoplasty. We reviewed our cases of gastrocystoplasty to determine the long-term incidence and significance of the syndrome. MATERIALS AND METHODS: We performed a retrospective study of 78 patients who underwent gastrocystoplasty at our institution between July 1989 and October 1994. A total of 72 of the 78 cases were evaluated within the last year to elicit symptoms of the hematuria-dysuria syndrome. RESULTS: Spina bifida and bladder exstrophy were the most common diagnoses of patients undergoing gastrocystoplasty. There were 3 (4%) patients who required medications on a continuous basis to control symptoms of the hematuria-dysuria syndrome. However, using broad criteria 17 (24%) patients would be categorized as having the syndrome. Of these patients 9 did not require any medications and 4 occasionally took medications to control symptoms. A significant increase in the incidence of the hematuria-dysuria syndrome was detected in those cases with a sensate compared to those with an insensate urethra. CONCLUSIONS: The hematuria-dysuria syndrome is a clinically significant problem at long-term followup in a small percentage of patients treated with gastrocystoplasty. The lowest incidence is in those children with an insensate urethra who are continent. When symptoms occur they are easily treated in the majority of cases. We believe that gastrocystoplasty remains a viable option in the armamentarium of bladder augmentation.

Effect of transfusional iron overload on immune response.

Increased susceptibility to infectious disease is observed in persons with transfusion-dependent thalassemia and iron overload who experience increased exposure to pathogens and chronic immune stimulation. An abnormal low CD8(+) T (LT8) immune phenotype defines a subgroup of patients. The CD8(+) T cell immunophenotype is stable despite continued blood transfusion and is independent of age. CD8(+) T cells, but not CD4(+) T cells, were modulated during intravenous chelation with deferoxamine. Return to characteristic pretreatment levels of CD8 was observed in both the low and the normal groups, suggesting the possibility of a set point. Proliferative response to mitogens and antigens was increased by chelation. Because CD8(+) T cells are important in immune response to infectious disease, these studies suggest that intrinsic CD8(+) T cell subset differences may be a critical factor in determining susceptibility to infection independent of transfusional iron overload or alloantigen exposure.

Complete primary repair of exstrophy.

PURPOSE: The surgical correction of bladder exstrophy to achieve continence with voiding remains a challenging problem for the urologist. Since 1989 we have performed complete primary repair for exstrophy based on the concept that the primary defect of bladder and cloacal exstrophy is anterior herniation. Thus, the bladder and urethra must be treated as a single unit to move them posteriorly into the pelvis. We present this technique. MATERIALS AND METHODS: From 1989 to 1997, 18 patients with bladder exstrophy and 6 with cloacal exstrophy underwent complete primary repair of exstrophy. This procedure was done on day 1 of life in 18 patients. Mean followup is 44 months (range 4 months to 8 years). RESULTS: At a median followup of 48 months 4 boys and 4 girls have volitional voiding after complete primary repair of bladder exstrophy, 21 patients have continent intervals and 2 boys void with continent intervals after complete primary repair of cloacal exstrophy. No patient has had a loss of renal function in this series. Postoperative complications included urethrocutaneous fistula formation in 2 cases. No patient had primary closure dehiscence. CONCLUSIONS: The rate of urinary continence achieved with complete primary repair compares favorably to that of staged repair for exstrophy. Complete primary repair also minimizes the number of surgical procedures required to achieve urinary continence and potentiates bladder neck function that permits bladder cycling in year 1 of life. The complication rates of these techniques are significantly lower than those reported in previous series of primary closure of exstrophy.

Complete primary closure of bladder exstrophy. Epispadias and bladder exstrophy repair.

Bladder exstrophy remains one of the most challenging problems in pediatric urology. Recent efforts have focused on primary reconstruction rather than urinary diversion to treat exstrophy. Complete primary closure appears to offer improved continence and decreases the number of surgical procedures required to treat exstrophy.

Laparoscopic and histologic evaluation of the inguinal vanishing testis.

OBJECTIVES: Visual inspection of the spermatic cord vessels and vas deferens during laparoscopy now frequently determines further treatment. We set out to explore the implications of atretic spermatic cord vessels and vas deferens entering the inguinal ring, a finding noted on laparoscopic examination in some patients with a nonpalpable testis, and that we refer to as the inguinal vanishing testis. METHODS: We reviewed our series of 35 patients with nonpalpable testes with regard to the laparoscopic, surgical, and histopathologic findings of the involved gonadal structures. RESULTS: We noted atretic vessels and vas deferens entering the inguinal ring in 14 patients in this series. All 14 patients underwent open inguinal exploration. Histopathologic findings revealed fibrosis and hemosiderin deposits alone in 13 patients. One specimen had a microscopic focus of residual seminiferous tubules. No specimen contained dysgenetic gonadal tissue. CONCLUSIONS: We submit that patients with inguinal vanishing testes do not need to undergo inguinal exploration to remove residual testicular tissue. Only rarely will viable seminiferous tubules be found, so the risk of malignant degeneration is remote. The histopathologic findings suggest that the inguinal vanishing testis occurs secondary to a vascular accident in utero or in the neonatal period.

Antiretroviral effects of deoxyhypusyl hydroxylase inhibitors: a hypusine-dependent host cell mechanism for replication of human immunodeficiency virus type 1 (HIV-1).

The HIV-1 protein Rev, critical for translation of incompletely spliced retroviral mRNAs encoding capsid elements, requires a host cell protein termed "eukaryotic initiation factor 5A" (eIF-5A). This is the only protein containing hypusine, a lysine-derived hydroxylated residue that determines its proposed bioactivity, the translation of a subset of cellular mRNAs controlling G1-to-S transit of the cell cycle. We postulated that inhibiting the hypusine-forming deoxyhypusyl hydroxylase (DOHH) should, by depleting eukaryotic initiation factor 5A, compromise Rev function and thus reduce HIV-1 multiplication. We now report that the alpha-hydroxypyridones, specifically mimosine, a natural product, and deferiprone, an experimental drug, inhibited deoxyhypusyl hydroxylase in T-lymphocytic and promonocytic cell lines and, in a concentration-dependent manner, suppressed replication of HIV-1. However, the alpha-hydroxypyridones did not affect the formation of unspliced or multiply spliced HIV-1 transcripts. Rather, these agents caused Rev-dependent incompletely spliced HIV-1 mRNA such as gag, but not cellular "housekeeping" mRNAs, to disappear from polysomes. Consequently, alpha-hydroxypyridone-mediated depletion of eIF-5A decreased biosynthesis of structural HIV-1 protein encoded by gag, measured as p24, whereas the induced formation of cellular protein like tumor necrosis factor alpha remained unaffected. By interfering with the translation of incompletely spliced retroviral mRNAs, these compounds restrict HIV-1 to the early, nongenerative phase of its reproductive cycle. In the inducibly HIV-1 expressing T-cell line ACH-2, the deoxyhypusyl hydroxylase inhibitors triggered extensive apoptosis, particularly of cells that actively produce HIV-1. Selective suppression of retroviral protein biosynthesis and preferential apoptosis of retrovirally infected cells by alpha-hydroxypyridones point to a novel mode of antiretroviral action.

Newborn exstrophy closure and epispadias repair.

Over the last 150 years, bladder exstrophy has undergone a transition from a primarily nonsurgically treated disease to a disease treated by urinary diversion or staged repair and now, possibly, primary newborn reconstruction. Our enthusiasm for primary reconstruction arises because of its potential to simplify the management of this disorder and optimize the return of normal bladder function for these patients. As with most new concepts, the evolution of our primary reconstruction techniques could not have been achieved without the prior efforts of others. Other surgeons such as H.H. Young and J. Ansell have shown us the possibility of achieving urinary continence with primary newborn exstrophy closure without sacrificing renal function, but the results have been inconsistent in the past. Staged reconstruction for bladder exstrophy demonstrates the possibility to achieve consistent successful rates of continence in these patients. However, multiple surgical procedures are required to attain this success. The preliminary results of our series of primary bladder exstrophy closures has encouraged us to perform it for all neonates referred to our institution with bladder exstrophy as well as to use it as part of staged reconstructive efforts for patients who have undergone primary surgical procedures for exstrophy elsewhere. We are hopeful and optimistic that newborn primary exstrophy closure performed as described herein will produce consistent rates of urinary continence and allow normal voiding function as well.

Epidemiological features of testicular teratoma in a prepubertal population.

PURPOSE: Prepubertal teratomas of the testis are rare benign tumors. Knowledge of the epidemiology of testicular teratomas and associated alpha-fetoprotein (AFP) levels could assist in planning treatment for prepubertal patients suspected of having teratoma of the testis. MATERIALS AND METHODS: We evaluated data on testicular teratoma from the Prepubertal Testis Tumor Registry of the Section on Urology of the American Academy of Pediatrics. RESULTS: Median patient age at presentation was 13 months. Teratomas occurred equally in the right and left testes. Most patients presented with a scrotal mass. Preoperative AFP levels were elevated in 20 of the 34 patients and postoperative levels were elevated in 9 of 10. Most patients were treated with radical orchiectomy and no metastatic disease was reported. CONCLUSIONS: Data in the registry confirm the benign nature of this tumor. Normal AFP levels should not be expected in infants with teratoma.

Serum ferritin iron, a new test, measures human body iron stores unconfounded by inflammation.

Serum ferritin protein is an acute phase reactant. We hypothesized that serum ferritin protein generated in response to an inflammatory process would have much less iron (Fe) in it than would "normal" ferritin protein, and therefore measuring serum ferritin iron would assess human body iron status unconfounded by inflammation. BASIC METHODS: We measured serum ferritin iron in 140 clinical samples obtained from the serum banks of Bronx VA Medical Center Hematology and Nutrition Laboratory (Bronx, NY), the CDC Nutritional Biochemistry serum sample bank (Atlanta, GA), and the sample bank from patients with thalassemia and iron overload treated at New York Hospital (New York, NY). Each was analyzed for three conventional criteria of iron status: serum iron, percentage of transferrin saturation and ferritin protein. In addition, tests for inflammation were also performed: C-reactive protein, WBC and transaminases. Seventy-seven patients' sera from 140 screened met each of three consistent criteria for stages of iron status. Serum ferritin was immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose and separated from other iron-containing proteins, digested with 0.2 ml of 3N nitric acid and analyzed for iron content by atomic absorption spectroscopy. RESULTS: Serum ferritin iron ranged in normal controls from 10 ng to 35 ng Fe/ml. The patients with iron deficiency (4/4) and those in negative iron balance (5/6) had values < or = 10 ng. Positive iron balance (8/9) and iron overload (22/22) values were > 35 ng/ml, in contrast to 11/19 with inflammation. Seventeen of twenty-two with overload had values > 100 ng/ml while only 1/19 with inflammation had such a value. Ferritin iron in ferritin protein was > 15% by weight in 14/22 with iron overload but in 0/19 with inflammation. IMPLICATIONS OF THE WORK: Serum ferritin iron is a simple, direct measure of iron stores that we propose, in conjunction with measuring serum ferritin protein, as a minimally invasive screening procedure for accurately assessing the whole range of human body iron status, unconfounded by inflammation.

Renal pathology in patients with primary hyperaldosteronism secondary to an adrenal cortical adenoma.

OBJECTIVES: The cause of persistent hypertension following the removal of an aldosterone-producing adrenal adenoma is unknown. The purpose of this study was to determine whether this occurrence is due to existing renal histopathologic damage. METHODS: Thirty-two patients with primary hyperaldosteronism due to an aldosterone-secreting adrenal cortical adenoma underwent open renal biopsy at the time of unilateral adrenalectomy. Biopsy results were correlated with the duration and severity of hypertension before and after surgery. RESULTS: Nineteen patients were cured of their hypertension postoperatively, whereas 13 patients had persistent diastolic hypertension. Statistical analysis of these two groups revealed no difference when renal histopathologic variables, preoperative severity of hypertension, or preoperative duration of hypertension were compared. CONCLUSIONS: Persistent hypertension in these patients does not appear to be due to renal histopathologic changes; coexisting essential hypertension is a more likely cause.

Trophozoite elimination in a rat model of Pneumocystis carinii pneumonia by clinically achievable plasma deferoxamine concentrations.

In a rat model of Pneumocystis carinii pneumonia, a 3-week infusion of deferoxamine producing concentrations in plasma of > or = 1.5 micrograms m-1 eliminated the trophozoite life cycle stage. Since this concentration is well below that routinely achieved in patients treated for iron overload, deferoxamine has promise as a therapy for AIDS-associated P.carinii pneumonia.