The nonreplicating smallpox candidate vaccines defective vaccinia Lister (dVV-L) and modified vaccinia Ankara (MVA) elicit robust long-term protection.

Current smallpox vaccines are live vaccinia viruses that replicate in the vaccinee inducing immunity against the deadly disease smallpox. Replication resulting in virus spread within the host, however, is the major cause of severe postvaccinal adverse events. Therefore, attenuated strains such as modified vaccinia Ankara (MVA) or LC16m8 are candidates as next generation vaccines. These strains are usually grown in primary cells in which mass production is difficult and have an unknown protective potential in humans. Proven vaccine strains of defined origin and modern production techniques are therefore desirable. In this study, defective vaccinia virus (dVV) lacking a gene essential for replication (derived from the Lister vaccine in a complementing cell line) was compared with the Wyeth smallpox vaccine strain and with MVA in mouse animal models using cowpox and ectromelia virus challenge. Similar to MVA, prime-boost immunizations with defective vaccinia induced robust long-term immunity, suggesting it as a promising next generation smallpox vaccine.

Immunogenicity and safety of defective vaccinia virus lister: comparison with modified vaccinia virus Ankara.

Potent and safe vaccinia virus vectors inducing cell-mediated immunity are needed for clinical use. Replicating vaccinia viruses generally induce strong cell-mediated immunity; however, they may have severe adverse effects. As a vector for clinical use, we assessed the defective vaccinia virus system, in which deletion of an essential gene blocks viral replication, resulting in an infectious virus that does not multiply in the host. The vaccinia virus Lister/Elstree strain, used during worldwide smallpox eradication, was chosen as the parental virus. The immunogenicity and safety of the defective vaccinia virus Lister were evaluated without and with the inserted human p53 gene as a model and compared to parallel constructs based on modified vaccinia virus Ankara (MVA), the present "gold standard" of recombinant vaccinia viruses in clinical development. The defective viruses induced an efficient Th1-type immune response. Antibody and cytotoxic-T-cell responses were comparable to those induced by MVA. Safety of the defective Lister constructs could be demonstrated in vitro in cell culture as well as in vivo in immunodeficient SCID mice. Similar to MVA, the defective viruses were tolerated at doses four orders of magnitude higher than those of the wild-type Lister strain. While current nonreplicating vectors are produced mainly in primary chicken cells, defective vaccinia virus is produced in a permanent safety-tested cell line. Vaccines based on this system have the additional advantage of enhanced product safety. Therefore, a vector system was made which promises to be a valuable tool not only for immunotherapy for diseases such as cancer, human immunodeficiency virus infection, or malaria but also as a basis for a safer smallpox vaccine.

[Bardet-Biedl syndrome: aspects of nephro-urology and human genetics]. / Bardet-Biedl-Syndrom: nephrourologische und humangenetische Aspekte.

Bardet-Biedl syndrome is a genetically heterogeneous autosomal recessive complex of features in which five gene loci have been described up to now. The diagnosis of this rare syndrome is based on the main manifestations hypogonadism, age-dependent increasing obesity and reduction of renal function, age-dependent progressive retinal degeneration with blindness as well as postaxial polydactyly and mental retardation. The life expectancy is short. Problems of early diagnostics, secondary hyperparathyroidism as well as surgical reconstruction of the genitals and kidney replacement therapy are discussed.

Combination of hypospadias and maldescended testis as cardinal symptoms in gonosomal chromosome aberrations.

Intersexual genitals or distinct hypospadias in combination with maldescended testis can be caused by endocrinological as well as chromosomal abnormalities. Even in early childhood such clinical findings require specific diagnostic procedures and subsequent treatment which is often invasive but has special importance as regards the early diagnosis of gonadal tumors. We present a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadias. Cytogenetic analyses revealed a mosaic karyotype 45, X/46, X, idic (Yp) with unequal distribution of the mosaic in different tissues. In consequence of this chromosomal aberration the patient had mixed gonadal dysgenesis which is associated with an increased risk of tumor development in the aberrant gonads. The principles of pediatric, urological, cytogenetic and endocrinological diagnostics and the mode of data collection in the presented case are described and discussed. Furthermore, a protocol for preventive screening is presented, which combines urological and endocrinological investigations in males with malformations of the genito-urinary tract to minimize the risk of tumor development in the aberrant gonads.

A new suprapubic cystostomy trocar system.

We describe a newly developed suprapubic catheterization set with a defined sigmoidal, geometrically and functionally tripartite tip and grooved trocar shaft. The device was designed to enhance the handling and safety features of the current commercially available sets to promote the broader application of suprapubic catheterization.

Humoral and cell-mediated immunity to vero cell-derived influenza vaccine.

A candidate trivalent influenza whole virus vaccine produced in a continuous mammalian cell line (Vero), and analogous commercially available egg-derived vaccines, were compared for their ability to induce humoral and cell-mediated immunity in Balb/c mice. Substantial haemagglutination-inhibition titre and high levels of influenza virus-specific IgG were found in all groups of immunized mice, irrespective of the vaccine formulation. The IgG responses were predominantly of IgG1 and IgG2a/2b isotypes. Virus-specific secretory IgA antibodies were detected only in mice immunized intranasally with a live virus, derived either from Vero cells or eggs. T-cell proliferative responses and T-helper 1 type cytokine release was significantly higher in mice immunized with Vero cell-derived influenza vaccine compared to egg-derived vaccine formulations. We have demonstrated that the immunogenicity of the trivalent Vero cell-derived whole influenza virus vaccine was comparable to that of the equivalent egg-derived vaccine, with respect to humoral immune response and was superior with respect to cellular response.

Humoral and cellular immunity induced by antigens adjuvanted with colloidal iron hydroxide.

The immunopotentiating activities of colloidal iron hydroxide, a novel, experimental mineral adjuvant, and of aluminium hydroxide. the licensed adjuvant for human vaccines, were compared. Our studies revealed that colloidal iron hydroxide and aluminium hydroxide behaved comparably with respect to supporting induction of an antibody response to tetanus toxoid. Furthermore, mice immunized with both, the experimental vaccine (tick-borne encephalitis virus (TBEV) antigen adsorbed to colloidal iron hydroxide) or with a commercially available TBEV vaccine (adjuvanted with aluminium hydroxide), developed long-lasting antibody responses which protected the animals from TBEV infection even one year after vaccination. The use of colloidal iron hydroxide as adjuvant had the additional advantage to reproducibly support induction of HIV-1 envelope-specific cytotoxic T lymphocytes (CTL), when used as adjuvant for a HIV-1 env-carrying recombinant fowlpox virus and being applied via the subcutaneous route. Aluminium hydroxide was much less active in this respect. Non-adjuvanted recombinant fowlpox elicited CTLs only when given intravenously or intraperitoneally, vaccination routes considered not to be suitable for routine use in humans. Further studies to evaluate the use of colloidal iron as possible alternative and/or supplement for routinely used mineral adjuvants may therefore be warranted.

[Urinary incontinence in neurogenic defects and urogenital anomalies in childhood]. / Harninkontinenz bei neurogenen Defekten und Urogenitalanomalien im Kindesalter.

Dysraphic defects may cause neurogenic incontinence in childhood. Constipation and encopresis are often associated. Depending on the involved segment of the spinal cord hyperreflexia or atonia of the detrusor is observed. Similar findings, without anatomic correlation, can be seen in occult-neurogenic voiding dysfunctions. Therapeutic means aim at preservation of kidney function and the best possible continence. If the symptoms cannot be treated by anticholinergic drugs in a low-capacity, hypertonic bladder, augmentation by bowel segments or continent urinary diversion (e.g. Mainz I pouch) is performed. In the last years modalities of clean intermittent self-catheterization in high-capacity, atonic bladders could be enhanced by the development of new atraumatic catheter systems. Urogenital malformation e.g. proximal epispadias and exstrophic bladder can cause incontinence as well. Recently, new therapeutic concepts were introduced. Ectopic ureter (extraurethral incontinence) in girls or posterior urethral valves in boys as a reason for incontinence must not be forgotten.

An experimental prime-boost regimen leading to HIV type 1-specific mucosal and systemic immunity in BALB/c mice.

Induction of mucosal as well as systemic immunity to HIV-1 is considered to have high priority in current concepts of future AIDS vaccines. Here we show that the desired immune responses can be elicited by an experimental prime-boost regimen consisting of mucosal (intragastric) application of a recombinant vaccinia virus carrying the HIV-1 env gene (vSC25), followed by parenteral (intradermal) immunization with the recombinant HIV-1 glycoprotein 160 (rgp160). Following intragastric immunization of mice with vSC25 in combination with the mucosal adjuvant cholera toxin (CT), HIV-1 env-specific IgA was secreted by B cells of Peyer's patches and the lamina propria. Moreover, mucosal (intragastric and intranasal) application of vSC25 (both in presence or absence of CT) induced a long-lasting, HIV-1 env-specific systemic cytotoxic T cell response. Subsequent intradermal boosters with rgp160 led to HIV-1-specific T cell memory and serum antibodies.

[Undescended testis and hypospadia in sex chromosomal aberrations]. / Maldescensus testis und Hypospadie bei Aberration der Geschlechtschromosomen.

If hermaphrodite genitals are present in the patient or a higher degree of hypospadia is shown with maldescensus testis, a chromosomal disorder must be considered as one potential cause of the anomaly. The case report of a child with cryptorchidism on the right, inguinal testis on the left and penoscrotal hypospadia is presented as an example. A mosaic karyotype 45, X/46, X, idic (Yp) was diagnosed in this patient after chromosomal analysis. The cell line with the isodicentric Y chromosome could be demonstrated in about 90% of the lymphocytes, but only in 7% of the fibroblasts of the preputium. A derivative Y could not be detected in interphase nuclei in the buccal mucosa, i.e. only the cell line with monosomy X was presented. There was thus chromosomal mosaicism with unequal tissue involvement and a high potential for malignant transformation. Guidelines of pediatric urological, cytogenetic and endocrinological investigations and the diagnostic procedures are described and discussed. A prevention protocol for patients with comparable gonosomal mosaicism is presented.

Nephrogenic adenoma in children. Case report and review of literature.

Nephrogenic adenoma in children is an extremely rare kind of tumor (22 cases have been described to date). We report and discuss here the case of a 7-year-old girl, taking into account the findings described in medical literature. In contrast to nephrogenic adenomas in adults, who present with this tumor in the entire ureteral tract, it has been observed exclusively in the bladder in children so far. The most frequent predisposing factors for the development of this tumor are extensive surgical injury such as ureter reimplantation or long-term stimuli on the urothelium caused by a foreign body. Diagnosis primarily includes sonography of the urinary tract and cystoscopy. Transurethral resection is regarded as the treatment of choice. Owing to the frequency of persistence, control cystoscopies after primary therapy are necessary.

Urological aspects of Munchausen's syndrome.

Munchausen's syndrome (MHS) is classed among the self-manipulated disease but is frequently not recognized as such. Patients suffering from MHS successfully obtain repeated invasive diagnostic management by the permanent presentation of various symptoms especially in the surgical branches of medicine. In urology, the 'hemorrhagic type', the 'abdominal type' and the 'neurological type' are predominant. In the course of his 'history' the MHS patient shows definite organic lesions as a result of numerous artificial and iatrogenic procedures. Consequently, diagnosis gets more and more difficult. In the majority of cases psychotherapy ends after few psychiatric interviews in the initial stage of therapy. Increasing somatic lesions are predominant.

Long-term results of internal urethrotomy.

PURPOSE: A retrospective analysis was done of long-term results of internal urethrotomy to evaluate risk factors of stricture recurrence. MATERIALS AND METHODS: Followup studies were performed of 937 patients with urethral strictures treated with internal urethrotomy. Of the patients 357 were treated at Mainz University between 1977 and 1989 (mean followup 4.6 years) and 580 were treated at Bonn University between 1974 and 1986 (mean followup 3.2 years). RESULTS: Strictures recurred in 96 of 357 (26.9%) and 260 of 580 (44.8%) patients, respectively. Risk factors for recurrence were etiology (post-transurethral resection and inflammation), stricture longer than 1 cm. and postoperative catheter drainage for longer than 3 days. CONCLUSIONS: Urethroplasty should be considered in patients at high risk for stricture recurrence and with more than 1 treatment failure after urethrotomy.

Noise emission zones in an automobile sheet-metal pressing plant, a 25-year follow-up study at three locations in the plant.

The Volvo plant at Olofström, Sweden is engaged in the pressing and assembling of sheet-metal components for automobiles. During the past 25 years, determined efforts have been made to introduce less noisy methods of production and to limit the levels of noise emission in three large workshops at the plant. Noise levels were mapped with the aid of stationary noise measurements. The results are expressed in terms of noise emission zones and presented as noise contour maps. The investigations were made on four occasions between 1967 and 1991. Following the comparative area calculations of the noise emission zones, it was deduced that the noise levels had been significantly reduced, despite an increased production. The results show that noise reduction measures applied to the presses. An increase in automation in sheet-metal handling, improved quality in the pressing of components and changes in the range of products have contributed to the reduction of noise levels at the plant.

Allostimulated lymphocytes inhibit replication of HIV type 1.

Previous reports demonstrated that alloantigen- or xenoantigen-specific antibodies displayed neutralizing activity toward human or simian immunodeficiency viruses. In the present article we have addressed the question of alloantigen-induced cell-mediated anti-HIV activity. We show that allostimulation resulted in a lymphocyte population (largely of the CD8-positive phenotype) with the capacity to inhibit HIV-1 replication in PHA blasts of homologous and, unexpectedly, also autologous origin. The allostimulated effector cells exerted their activity via a noncytolytic mechanism. Experiments in which direct cell-to-cell contact between allostimulated effectors and HIV-1-infected PHA blasts was prevented by a semipermeable membrane indicated that soluble mediators were involved in inhibition of HIV-1 replication. As such allostimulated effectors not only would have the capacity to prevent viral replication in allogeneic HIV-1-infected cells (known to play an important role in HIV-1 transmission in vivo), but also might inhibit HIV-1 growth in autologous lymphocytes, the concept of an AIDS vaccine containing both HIV-1 antigens and alloantigens warrants further consideration.

Lich-Gregoir anti-reflux procedure; indications and results with 283 vesicoureteral units.

While reflux is not the cause of the ascension of microorganisms into the urinary bladder, it enables bacteria to reach the kidney and fosters pyelonephritis, persistent infections and nephropathy with all related consequences. The efficiency of the Lich-Gregoir antireflux procedure must be judged by its results. The criterion of success in operations upon 225 children (283 vesicoureteral units) is the procedure's positive effect on renal growth and physical development of the patients by controlling pyelonephritis and the elimination of recurrent supravesical infections in more than 98 per cent of children operated upon.