Adolescent varicocele.

The evaluation and management of adolescents with varicoceles continue to evolve. Current recommendations for repair are based on the findings of impaired testicular growth or spermatogenesis; however, with early evaluation and selective treatment, clinicians should be able to reduce the potential for future fertility problems significantly in adolescents with varicoceles.

BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.

BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH helicase family. BACH1 binds directly to the BRCT repeats of BRCA1. A BACH1 derivative, bearing a mutation in a residue that was essential for catalytic function in other helicases, interfered with normal double-strand break repair in a manner that was dependent on its BRCA1 binding function. Thus, BACH1/BRCA1 complex formation contributes to a key BRCA1 activity. In addition, germline BACH1 mutations affecting the helicase domain were detected in two early-onset breast cancer patients and not in 200 matched controls. Thus, it is conceivable that, like BRCA1, BACH1 is a target of germline cancer-inducing mutations.

Varicocele in adolescence induces left and right testicular volume loss.

OBJECTIVE: To determine the effect of a palpable left-sided varicocele (which in adolescent patients can adversely affect left testicular volume) on right testicular volume with progressive Tanner development and increasing varicocele grade. PATIENTS AND METHODS: The right and left testicular volumes were measured with a standard orchidometer in 70 control patients (mean age 14.6 years, SD 2.2) with no palpable testicular abnormality and in 434 (mean age 14.3 years, SD 2.3) with a palpable left-sided varicocele. Patients with bilateral and right-sided varicoceles were excluded from the study. RESULTS: There was no significant difference between the left and right testicular volumes in the control patients. The testicular volumes of patients with a grade I varicocele were similar to those in control patients. Patients with a grade II varicocele had a significantly smaller left testis than the controls at Tanner stages 4 and 5 (P < or = 0.05). Patients with a grade III varicocele had a significantly smaller left testis than controls at each Tanner stage (P < or = 0.05) and significantly smaller right testis than controls at Tanner stages 4 and 5 (P < or = 0.05). CONCLUSION: The presence of a grade I varicocele in adolescence appears to have no effect on normal testicular growth. Some patients with a grade II varicocele are at risk of left testicular volume loss with time and should have their testicular volume measured annually. Patients with grade III varicocele are at risk of bilateral testicular volume loss; a careful evaluation and early surgical intervention are recommended in this group of patients.

Granulocyte/macrophage-colony stimulating factor produced by recombinant avian poxviruses enriches the regional lymph nodes with antigen-presenting cells and acts as an immunoadjuvant.

Recombinant avian poxviruses [fowlpox and canarypox (ALVAC)], restricted for replication in nonavian cell substrates and expressing granulocyte/macrophage-colony stimulating factor (avipox-GM-CSF), were evaluated for their ability to enrich an immunization site with antigen-presenting cells (APCs) and, in turn, function as biological vaccine adjuvants. Avipox-GM-CSF administered as a single s.c. injection significantly enhanced the percentage and absolute number of APCs in the regional lymph nodes that drain the injection site. Both the magnitude and duration of the cellular and phenotypic increases within the lymph nodes induced by the avipox-GM-CSF viruses were significantly (P < 0.05) greater than those measured in mice treated with four daily injections of recombinant GM-CSF protein. Temporal studies revealed that the APC enrichment of regional lymph nodes was sustained for 21-28 days after injection of the recombinant avipox virus expressing GM-CSF and, moreover, three injections of the recombinant virus could be given without any appreciable loss of in vivo bioactivity. Mice expressing human carcinoembryonic antigen (CEA) as a transgene (CEA.Tg) developed CEA-specific humoral and cell-mediated immunity after being immunized with avipox-CEA. The coadministration of recombinant avipox viruses expressing CEA and GM-CSF significantly enhanced CEA-specific host immunity with an accompanying immunotherapeutic response in tumor-bearing CEA.Tg mice. The optimal use of avipox-GM-CSF, in terms of dose and dose schedule, especially when used with different immunogens, remains to be determined. Nonetheless, the present findings demonstrate: (a) the effective delivery of GM-CSF to an immunization site using a recombinant avian poxvirus; (b) the compatibility of delivering an antigen and GM-CSF in replication-defective viruses to enhance antigen-specific immunity; and (c) the combined use of recombinant avipox viruses expressing CEA and GM-CSF to generate antitumor immunity directed at a self tumor antigen.

Glanuloplasty and in situ tubularization of the urethral plate: long-term followup.

PURPOSE: We update our experience with glanuloplasty and in situ tubularization of the urethral plate for hypospadias repair first described in 1995, and report its indications and long-term results. MATERIALS AND METHODS: We evaluated the surgical results of glanuloplasty and in situ tubularization of the urethral plate for hypospadias repair in 308 patients. RESULTS: Overall cosmetic results were excellent. The overall complication rate for both series was 9.7%, and complications consisted of a urethral fistula in 9.1% and a urethral diverticulum in 0.6%. However, in our recent series the complication rate decreased to 1.7% for distal repairs and 7.7% for mid shaft hypospadias repair. CONCLUSIONS: Glanuloplasty with in situ tubularization of the urethral plate is an excellent technique for the majority of boys with distal and mid shaft hypospadias, producing a pleasing cosmetic appearance with a low complication rate.

Comparative studies of the effects of recombinant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen- presenting cells in regional lymph nodes.

Repeated subcutaneous (s.c.) injections of recombinant granulocyte-macrophage colony-stimulating factor (recGM-CSF) for 4-5 days can enrich an immunization site with antigen-presenting cells (APC), which has been correlated with improved immune responses in experimental and clinical studies. A recombinant vaccinia virus encoding the GM-CSF gene (rV-GM-CSF) has been developed and can generate specific antitumour immunity in a whole tumour cell vaccine. In the present study, we examined whether rV-GM-CSF could produce and release GM-CSF locally which, in turn, might enrich a site of immunization for APC as previously shown for recGM-CSF. S.c. injection of rV-GM-CSF significantly (P<0.05) enhanced the percentage and overall number of APC, measured by class II expression levels, in the regional lymph nodes that drain the injection site. Dose- and temporal-dependent studies showed class II expression levels in the draining lymph nodes were maximally enhanced 5-7 days after a single injection of 10(7)plaque-forming units (pfu) of rV-GM-CSF. Flow cytometry revealed that the increase in class II expression resulted from (i) a higher class II expression level on CD19(+)B cells and (ii) an increase in the number of CD11c(+)/class II(+)professional APC within the draining lymph nodes. Moreover, isolation of lymph nodes from rV-GM-CSF-treated mice revealed their capacity to support higher levels of antigen-specific T cell proliferation and allospecific cytotoxic responses. A comparison between a single injection of rV-GM-CSF and a 4-day course of recGM-CSF revealed comparable changes in class II expression and functional T cell assays. GM-CSF can be delivered in a recombinant poxvirus, and the local production of the cytokine results in cellular and phenotypic changes that are similar to those of recGM-CSF. The ability to utilize rV-GM-CSF as a single inoculum may be more compatible with traditional immunization strategies.

Paediatric urinary tract infection and the necessity of complete urological imaging.

OBJECTIVE: To evaluate voiding cysto-urethrography (VCUG) in assessing children with urinary tract infection (UTI) when renal/bladder ultrasonography and renal scintigraphy show no abnormality. PATIENTS AND METHODS: A total of 468 renal scintigrams taken in children for an indication of UTI between January 1996 and December 1998 were reviewed. The renal and bladder ultrasonograms of those children with a normal renal scan were then reviewed. Children with both normal renal scans and normal ultrasonography were then evaluated for the frequency and grade of vesico-ureteric reflux (VUR) on VCUG. RESULTS: Of the 468 patients, 453 (97%) had complete imaging studies; 152 of the children evaluated had normal renal scans, of whom 101 had a normal renal ultrasonogram. Twenty-three (23%) children with both a normal renal scan and renal/bladder ultrasonogram showed VUR on VCUG, of whom 14 had bilateral VUR and 13 grade III or higher VUR. CONCLUSION: This study indicates that about 23% of patients may have significant VUR despite both a normal renal scan and ultrasonogram. Therefore, VCUG remains important in evaluating and managing children with UTI.

Metabolic and genetic determinants of HDL metabolism and hepatic lipase activity in normolipidemic females.

The metabolic and genetic determinants of HDL cholesterol (HDL-C) levels and HDL turnover were studied in 36 normolipidemic female subjects on a whole-food low-fat metabolic diet. Lipid, lipoprotein, and apolipoprotein levels, lipoprotein size, and apolipoprotein turnover parameters were determined, as were genetic variation at one site in the hepatic lipase promoter and six sites in the apolipoprotein AI/CIII/AIV gene cluster. Menopause had no significant effect on HDL-C or turnover. Stepwise multiple regression analysis revealed that HDL-C was most strongly correlated with HDL size, apolipoprotein A-II (apoA-II), and apolipoprotein A-I (apoA-I) levels, which together could account for 90% of the variation in HDL-C. HDL size was inversely correlated with triglycerides, body mass index, and hepatic lipase activity, which together accounted for 82% of the variation in HDL size. The hepatic lipase promoter genotype had a strong effect on hepatic lipase activity and could account for 38% of the variation in hepatic lipase activity. The apoA-I transport rate (AI-TR) was the major determinant of apoA-I levels, but AI-TR was not associated with six common genetic polymorphism in the apoAI/CIII/AIV gene cluster.A simplified model of HDL metabolism is proposed, in which A-I and apoA-II levels combined with triglycerides, and hepatic lipase activity could account for 80% of the variation in HDL-C.

Induction of protective host immunity to carcinoembryonic antigen (CEA), a self-antigen in CEA transgenic mice, by immunizing with a recombinant vaccinia-CEA virus.

Human carcinoembryonic antigen (CEA) is a well-characterized oncofetal glycoprotein whose overexpression by human carcinomas has been a target for cancer immunotherapy. Transgenic mice that express CEA as a self-antigen with a tissue distribution similar to that of humans have been developed. This study investigates: (a) the responsiveness of the CEA transgenic (CEA.Tg) mice to endogenous CEA or CEA administered as a whole protein in adjuvant; and (b) whether the presentation of CEA as a recombinant vaccinia virus could generate CEA-specific host immunity. By and large, the CEA.Tg mice were unresponsive to CEA, as shown by the lack of detectable CEA-specific serum antibodies and the inability to prime an in vitro splenic T-cell response to CEA. Furthermore, the administration of whole CEA protein in adjuvant to CEA.Tg mice failed to elicit either anti-CEA IgG titers or CEA-specific T-cell responses. Only weak anti-CEA IgM antibody titers were found in those mice. In contrast, CEA.Tg mice immunized with recombinant vaccinia virus expressing CEA generated relatively strong anti-CEA IgG antibody titers and demonstrated evidence of immunoglobulin class switching. These mice also developed T(H)1-type CEA-specific CD4+ responses and CEA peptide-specific cytotoxicity. The ability to generate CEA-specific host immunity correlated with protection of the CEA.Tg mice against a challenge with CEA-expressing tumor cells. Protection against tumor growth was accomplished with no apparent immune response directed at CEA-positive normal tissue. The results demonstrate the ability to generate an effective antitumor immune response to a tumor self-antigen by immunization with a recombinant vaccinia virus. CEA.Tg mice should be an excellent experimental model to study the effects of more aggressive immunization schemes directed at established tumors with the possible development of accompanying autoimmune responses involving normal tissues.

Manometric study of paranasal sinus mucoceles.

A paranasal sinus mucocele is a chronic cystlike lesion characterized by slowly progressive remodeling and expansion of the surrounding osseous walls. If left untreated, it may cause significant facial deformity, ophthalmic disturbances, and, in the worst instance, intracranial complications. According to a review of the literature, there is a long-held view that positive pressure exists within paranasal sinus mucoceles; however, to our knowledge, pressure measurements have not been recorded in humans. In this study, pressure measurements were taken of 4 paranasal sinus mucoceles by means of an 18-gauge needle probe and an amplified pressure transducer. The average value was +15 cm H2O with a range of +4 to +39 cm H2O. This study confirms the long-standing assumption that positive pressure exists within paranasal sinus mucoceles. The magnitude of the pressure was comparable to that which was found to be associated with bone resorption in several previously published studies. Further studies are needed to determine whether positive pressure and osseous remodeling are causally related in this condition.

Color Doppler ultrasound evaluation of the acute scrotum.

Color Doppler ultrasound has been reported to be useful in ruling out testicular torsion in children. Some investigators, however, have continued to report false-positive and false-negative studies. Herein we review our institution's experience over the past 6 years. From January 1990 to December 1996, over 300 boys 21 years of age or less underwent color Doppler ultrasound for testicular pain and/or swelling. Presentation, ultrasound diagnosis, operative findings (where applicable), and subsequent course were assessed. Complete data was available for 243 boys (average age 10.36 years, range 1 day to 21 years). Fourteen boys were explored without imaging based on strong clinical findings and short duration of pain. Of these, 13 had torsion and 1 had epididymitis. Torsion was ruled out by ultrasound in 182 with 100% specificity verified on follow-up. Forty-five diagnoses of torsion by ultrasound were confirmed operatively. Two patients with equivocal scans also were explored: one had torsion, whereas the other had a torsed appendix. Ultrasonic findings are characterized. Additionally, two cases of false-negative ultrasound from outside institutions are discussed. In conclusion, color Doppler ultrasound can identify reliably those children with an acute scrotum who require exploration and exclude those children without testis torsion who would otherwise undergo needless surgery.

The acute scrotum.

Every boy with acute onset scrotal pain and swelling requires an immediate evaluation. Our protocol (Fig. 6) for the evaluation of these children is based on the history and physical examination combined with the selective use of imaging studies. When used appropriately, this protocol facilitates the rapid identification of children with torsion and minimizes the number of unnecessary scrotal explorations. When the duration of the pain is brief, and history and physical examination suggest that torsion is the most likely diagnosis, urgent surgical exploration without additional imaging studies is recommended. When it is not possible to definitely diagnose or exclude the diagnosis of testicular torsion, or when the duration of pain is greater than 12 hours, then diagnostic imaging can provide significant information. Color Doppler sonography is, in the authors' opinion, preferable to nuclear imaging for the evaluation of children with acute scrotums. When normal or increased blood flow is present, scrotal exploration is not required. When the study demonstrates decreased blood flow or does not provide a definite diagnosis, scrotal exploration is recommended. The authors recommend this approach because less than one third of these children have testicular torsion, and if routine scrotal exploration is performed for all boys with acute scrotums, a significant number of unnecessary surgical procedures will result.

Phylogenetic relationships in the Papilionoideae (family Leguminosae) based on nucleotide sequences of cpDNA (rbcL) and ncDNA (ITS 1 and 2).

Sequences of cpDNA (rbcL) were determined for 94 species and of ncDNA [ITS 1 + 2 regions (internal transcribed spacer) of rDNA] for 75 species representing mainly the papilionoid tribes Sophoreae, Thermopsideae Podalyrieae, Liparieae, Crotalarieae, and Genisteae. Sequence data were used to reconstruct the underlying molecular phylogeny. Several clusters and furcations were identical in the rbcL and ITS trees of the Papilionoideae, indicating that a reticulate evolution due to past hybridization of members from different tribes and genera is unlikely: The Sophoreae (especially Styphnolobium japonicum (syn. Sophora japonica) and Sophora secundiflora) are positioned at the base of the papilionoid tree, whereas some other Sophora species (Sophora davidii, flavescens, jaubertii, microphylla) are closely related to Thermopsideae/Podalyrieae. The Thermopsideae/Podylyrieae cluster (including Liparieae) shares ancestry with the Crotalarieae and Genisteae. Argyrolobium (African taxa) and Melolobium cluster between Crotalarieae and Genisteae. In the Genisteae three clusters are apparent: the monophyletic genus Lupinus, the Cytisus-, and the Genista-group. According to this analysis, the Cytisus-complex includes Cytisus, Lembotropis, Chamaecytisus, Spartocytisus, and Calicotome. The Genista-group consists of Genista, Teline, and Chamaespartium sagittale. Other genera (e.g., Adenocarpus, Argyrocytisus, Cytisophyllum, Erinacea, Laburnum, Petteria, Retama, Spartium, and Ulex) could not be attributed unequivocally to the Cytisus or Genista complex.

Electrosurgery for routine pediatric penile procedures.

PURPOSE: Traditional teaching in urology has been to avoid electrosurgical devices in penile surgical procedures. In the last several years cutting current has been routinely used on the penis for making skin incisions, degloving, creating Byars flaps and destroying skin bridges. The purpose of this study was to determine the complications and final outcomes of electro-surgery. MATERIALS AND METHODS: A 5-year retrospective chart review was done to determine the complications and final outcomes of exclusively using electrical current to perform pediatric penile procedures. RESULTS: Electrosurgery was used to perform the entire surgical dissection in 346 patients, including circumcision in 124, repeat circumcision in 68, penoscrotal fusion/chordee repair in 127 and skin bridge procedures in 27. All patients had a satisfactory cosmetic result. After correction of penoscrotal fusion, separation at the scrotal suture line in 2 patients healed secondarily without sequelae. There was no hematoma, tissue necrosis or skin sloughing and all surgery was performed on an outpatient basis. CONCLUSIONS: Electrosurgery can be used safely and effectively for routine penile procedures, providing a bloodless operative field and excellent cosmetic results.

Chronic maxillary atelectasis.

Chronic maxillary atelectasis is a descriptive term that refers to a persistent decrease in the sinus volume of the maxilla from inward bowing of the antral walls. Case reports with comparable clinical presentations have appeared sporadically in the literature; however, this disorder has remained poorly defined. The purpose of this study is to provide a formal definition of this condition by the establishment of diagnostic and staging criteria. A 10-year case analysis identified 22 adults, and a review of the literature revealed another 25. The average age at presentation in our study was 38.3 years. Most patients were symptomatic, and some presented with diplopia and hypoglobus. Inward bowing of the antral wall(s) and persistent opacification on computed tomography made the diagnosis. Chronic maxillary atelectasis was separated into three stages according to the degree of wall deformation. While most patients were symptomatic, a past history of absent or mild symptoms referable to the nose and sinuses was encountered more often in those patients with osseous wall deformation (p = .041). Mild or absent symptoms at the time of diagnosis should not be considered a negative risk factor for the development of facial deformity, especially if the sinus has features consistent with complete pneumatization. A middle meatal antrostomy appears to relatively safely correct the sinus problem, while orbital floor reconstruction for hypoglobus, found in stage III of the disease, can be accomplished effectively via a transconjunctival approach using a combination of bone allograft and porous polyethylene sheets.

Manometric study of complete ostial occlusion in chronic maxillary atelectasis.

The effect of complete ostial occlusion on static pressure within the human maxillary sinus has not been previously studied. In this study, a novel way to directly determine maxillary sinus pressure is described. Maxillary sinus pressures were measured in five patients with chronic maxillary atelectasis (CMA); these values were compared to values obtained from the contralateral side and from patients with chronic sinusitis. Measurements were made by introducing an 18-gauge needle probe through the membranous fontanel of the maxillary sinus and recording the pressure value with an amplified, pressure-sensitive transducer. The average value recorded in five patients with atelectasis of the maxillary sinus and complete ostial occlusion was -8.4 +/- 2.6 cm H20 (mean +/- standard deviation). Static pressure measurements of the contralateral antrum were isobaric, as were measurements found in patients with chronic sinusitis. This study reports for the first time the sinus pressure of completely occluded maxillary ostia in patients with CMA. These results may improve our understanding of the development of ostial occlusion and its role in the pathogenesis of CMA and sinusitis.