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Penile and urethral anomalies are common congenital disorders with some rare variations. For example, the floppy penis is dealt with in only a few publications with a small numbers of cases. Other anomalies have not been published at all, i.e., the ectopic penis. Some anomalies become apparent immediately at birth, others remain undiscovered until adolescence. To date there is no established classification system dealing with urethral and penile anomalies. Also, no established guidelines exist for diagnosing and treating these anomalies. Surgical corrections of penile and urethral anomalies should follow standardized procedures on the one hand, but must respect the individual anatomical situation on the other. Since genital anomalies are frequently part of a syndrome, interdisciplinary approaches are advisable. The following article presents a classification of penile and urethral anomalies. Since posterior urethral valves usually affect the bladder and upper urinary tract, this disorder is not included in this review.

Recent studies involving the analysis of process measurement signals have shown that the ‘noise’ components carry potentially useful diagnostic information not only regarding the operating conditions at the point of measurement but also regarding the status of the measurement system. This is particularly true if the primary sensor itself has a wide frequency response and the unconditioned signal is analysed. At first sight, it appears that electromagnetic flowmeters are particularly suitable in this respect because they are essentially non-invasive, their method of sensing does not influence the flow regime and they have no moving parts. However, because of the spurious signals which are developed at the electrodes, the measurement signal has to be obtained by modulating the magnetic field and synchronously demodulating the electrode signal, but this eliminates virtually all the ‘noise’ components of the original signal. For this study, this difficulty was circumvented by holding the excitation of the electromagnet constant for a brief period while the electrode signal was sampled. The ‘noise’ component in the sampled data was then separated from the other components by a high pass filter and analysed to provide diagnostic information regarding both the flow regime as well as the operational status of the associated process equipment. Unfortunately, this mode of operation precludes the ability of the flowmeter to measure the actual flow rate and, in any practical implementation of the concept, it would be necessary to arrange the signal processing system so that it operates in the conventional mode for the majority of the time, but is switched for a brief period to the alternative mode during which the ‘noise’ component of the electrode signal is gathered and then analysed to provide the diagnostic information.

The signal conditioning and processing circuits of conventional electromagnetic flowmeters have been designed to provide an accurate average flowrate measurement signal, principally for the purpose of process control. One consequence of this is that the ‘noise’ and other low frequency components of the electrode signal are suppressed. Hitherto, the possibility that they may carry potentially useful information has been overlooked, but there are studies which show that information regarding the flow regime can be identified by spectral analysis of the higher frequency or ‘noise’ components of the sensor signals from some other types of flowmeters. If the entire electrode signal is analysed, using well-established signal analysis methods, diagnostic information regarding the flow regime in which the flowmeter is operating can be recovered and several distinctly different flow regimes can be identified, such as increased turbulence, swirling flow, flow pulsations and two-phase flow, all of which adversely affect the performance of the flowmeter. This paper presents the results of laboratory simulations of these flow regimes and describes a fuzzy logic method for identifying them. It also suggests a change to the conventional mode of operation and signal processing which would enable the additional functions to be implemented without involving any modification to the design or construction of the conventional flowtube. The potential benefits which arise from its application include the identification of flow regimes which adversely affect the performance of the flowmeter in its installed position and the ability to verify, on line, that the flowmeter is functioning correctly.

Maintenance of process equipment is one of the inescapable tasks associated with the operation of process plants and, until relatively recently, it was implemented either on a routine basis or after the failure of equipment. Attitudes are changing and now many organizations are adopting methods for identifying incipient faults, so that maintenance can be scheduled before there has been a failure which would lead to loss of production and spoilage of raw material. These methods include schemes in which all the measurement signals in a plant are gathered and, in addition to providing the input to the various control systems, they are compared with model-based values for individual sections throughout the entire process, so that a warning or an alarm can be raised, according to the seriousness of the observed discrepancy. Although these methods represent a considerable advance on ‘routine maintenance’ and ‘repair after failure’, their effectiveness is limited by the quality and detail of the information that is gathered. Each process measurement should be regarded as a ‘window’ through which the operation of the process can be observed. However, the majority of existing process measurement systems have been designed to provide the input signal to a process control system, for which the primary requirement is a good average value. Typically, this is obtained by filtering out all the components of the sensor signal having frequencies greater than about 5 Hz, with the result that the ‘window’ is only translucent, rather than transparent, and much of the detailed information which is available at the interface between the process and the sensor is lost. If, on the other hand, the measurement system has a wide frequency response, then much of the information that is available at the interface between the process and the sensor can be gathered and analysed to provide a clear view of the operation and status of both the process and the measurement system. This concept involves two significant departures from the conventional approach to process measurements and to the utilization of measurement information. In the first place, the measurement systems should be designed to have the widest possible frequency response, so that the maximum information regarding the measured process parameter that is present at the interface between the process and the sensor is gathered. Secondly, instead of conditioning the primary sensor signal to provide a good average value for process control, it is analysed using well established techniques to provide not only the signal for process control but also information on which predictive maintenance procedures can be based.

Reported here is the successful multi-staged repair of a rare case of complete penoscrotal transposition with ectopic penis. The need to evaluate for associated anomalies is discussed.

We report our efforts to create an ideal continent urinary catheterizable stoma.Our approach includes the creation of a continent stoma using a preputial penile island skin flap in male patients and a preputial clitoral island skin flap in female patients. The flaps are transposed suprapubically, tubularized and implanted in a nonrefluxing manner into the bladder or other urinary reservoir.From 1994 to April 1995 the technique was performed in 14 male patients 4 months to 42 years old and 7 female patients 4 to 14 years old. Early results were satisfactory at 2 to 12 months of follow up (mean 6).This technique could be an alternative to other methods of urinary continent diversion.

To establish the so-called positive screening instead of the current opportunistic screening for cervical cancer.The program of positive screening covered all female persons aged 30-49 years living in the Branicevo District. All women were sent an invitation to participate in the screening and those who responded had Papanicolaou smear test done on the results of which further diagnostic procedures would be determined.The invitation to examination was responded by 11,200 (48.70%) out of 23,000 women invited. The costs of organized screening per capita amounted to Republic of Serbia dinar (RSD) 380.00 (EUR 4.75). 954 patients in total underwent colposcopy and conization, resulting in RSD total costs of 11,926,373.70 (149,079.00 EUR). Assuming the same incidence rate among the population that did not respond to the invitation, the number of women that would have such an intervention would be increased by 893.One-year screening programme is more effective than 3-year programme (180 lives saved compared to 113), but more expensive. This is our cost-effectiveness analysis (CEA) relevant opinion, but not for adoption in practice.

Background: Fecal incontinence is common in children with anorectal anomalies or spina bifida. If it is possible to achieve fecal control, patients are given a large volume of enema once a day. Retrograde enemas are often unpleasant in children, particularly in adolescents. Malone procedure of antegrade appendicostomy achieves antegrade colonic irrigation. Material and Methods: From 1996 to 2003 Malone antegrade appendicostomy was performed in 10 patients with fecal incontinence. The patients were aged from 5 to 24 years. In 4 patients fecal incontinence was due to an anorectal anomaly, and in 6 patients spina bifida. Preoperatively, all patients were given a clysma to control fecal incontinence. The patients, who remained clean with regular usage of the clysma for 24 hours or longer, fulfilled the criterion for the formation of continent appendicostomy. In 9 patients the cecal appendix was used to create a stoma, while in another one a lateral tubularized cecal flap was applied. In 3 patients a continent conduit was also done due to urinary incontinence. The follow-up period was from 1 to 8 years. A patient was reoperated due to stenosis of the stomal aperture, while another one has not been using the stoma because of social reasons. Conclusion: Continent appendicostomy is a simple surgery, which is effective in the control of fecal incontinence in most children. It is indicated only in patients in whom the rerograde clysma successfully cleans the colon and if patient and parents are motivated to use it. Possible complications, among which stenosis is the most frequent, can be solved with a reoperation.

Penile and urethral anomalies are common congenital disorders with some rare variations. For example, the floppy penis is dealt with in only a few publications with a small numbers of cases. Other anomalies have not been published at all, i.e., the ectopic penis. Some anomalies become apparent immediately at birth, others remain undiscovered until adolescence. To date there is no established classification system dealing with urethral and penile anomalies. Also, no established guidelines exist for diagnosing and treating these anomalies. Surgical corrections of penile and urethral anomalies should follow standardized procedures on the one hand, but must respect the individual anatomical situation on the other. Since genital anomalies are frequently part of a syndrome, interdisciplinary approaches are advisable. The following article presents a classification of penile and urethral anomalies. Since posterior urethral valves usually affect the bladder and upper urinary tract, this disorder is not included in this review.

Kongenitale Harnrohendivertikel sind sowohl bei Kindern als auch bei Erwachsenen selten [2, 4, 8]. Zu den erworbenen Formen zahlen auch Harnrohrendivertikel, die postoperativ entstehen und zu den bekannten Komplikationen nach dem Harnrohrenaufbau bei den Hypospadien gehoren [1, 6, 7]. Das Harnrohrendivertikel manifestiert sich mit ventraler Aussackung der Neoharnrohre bei der Miktion (Abb. 1), abgeschwachtem Harnstrahl, und Palmurie. Harnwegsinfekte und Harnrohrensteine konnen sekundar auftreten [4, 8].

Recently, we reported that cells from the sponge Suberites domuncula respond to ethylene with an increase in intracellular Ca(2+) level [Ca(2+)](i), and with an upregulation of the expression of (at least) two genes, a Ca(2+)/calmodulin-dependent protein kinase and the potential ethylene-responsive gene, termed SDSNZERR (A. Krasko, H.C. Schröder, S. Perovic, R. Steffen, M. Kruse, W. Reichert, I.M. Müller, W.E.G. Müller, J. Biol. Chem. 274 (1999)). Here, we describe for the first time that also mammalian (3T3) cells respond to ethylene, generated by ethephon, with an immediate and transient, strong increase in [Ca(2+)](i). Next, the promoter for the sponge SDSNZERR gene was isolated from S. domuncula. It was found that the SDSNZERR gene is positioned adjacent to the SNZ-related gene (SNZ-proximal open reading frame) (SDSNO) and linked, as in Saccharomyces cerevisiae, in a head-to-head manner. Until now, neither homologues nor orthologues of these two genes have been identified in higher metazoan phyla. The full-length genes share a bidirectional promoter. 3T3 cells were transfected with this promoter; the activity of the SDSNZERR promoter was strong and twice as high as that of the SV40 promoter, while the SDSNO promoter was less active. Surprisingly, the activity of the SDSNZERR promoter could not be modulated by ethylene or salicylic acid while it is strongly upregulated, by 4-fold, under serum-starved conditions. It is concluded that the modulation of the level of [Ca(2+)](i) by ethylene in mammalian cells is not correlated with an upregulation of the ethylene-responsive gene SDSNZERR. The data indicate that in mammalian cells, the activity of the SDSNZERR promoter is associated with the repression of serum-mediated growth arrest.

Flupirtine is a triaminopyridine analogue which has been successfully applied in clinics as a non-opiate analgesic drug. Previously we described that flupirtine acts like an N-methyl-D-aspartate (NMDA) receptor antagonist in neuronal cells both in vitro and in vivo. Here we show that flupirtine displays its anti-apoptotic effect also in hNT (human Ntera/D1) neurons. hNT neurons were induced to apoptosis applying glutamate (Glu; at concentrationsor = 1 mM) or NMDA (or = 1 mM). During Glu/NMDA-mediated apoptosis the levels of the intracellular anti-apoptotic agents Bc1-2 and glutathione dropped by more than 50%. Flupirtine completely abolished this reduction of Bc1-2 and glutathione level at a concentration of 10 microM. In the presence of 3 microM flupirtine a6-fold increase of the Bc1-2 (B-cell leukemia/lymphoma-2) level was observed in hNT neurons. At the same concentration, the intracellular level of glutathione increased to 200%. We conclude that the Glu/NMDA-mediated neuronal cell death in vitro is controlled at least partially by Bc1-2 and glutathione. Neuronal cell death by Glu or NMDA in vitro can be overcome applying the drug flupirtine which is in clinical use.

Incubation of highly enriched neurons from rat cerebral cortex with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 18 h results in fragmentation of DNA at internucleosomal linkers, a feature of apoptosis. We report that neurons respond to exposure to gp120 with an increased release of arachidonic acid via activation of phospholipase A2. This process is not inhibited by antagonists of the N-methyl-D-aspartate (NMDA) receptor channels. To investigate the influence of arachidonic acid on the sensitivity of NMDA receptor towards its against, low concentrations of NMDA were coadministered with arachidonic acid. Under these conditions the NMDA-mediated cytotoxicity was enhanced. We conclude that gp120 causes an activation of phospholipase A2, resulting in an increased release of arachidonic acid which in turn sensitizes the NMDA receptor. Two compounds were found to act cytoprotectively against the deleterious effect caused by gp120 on neurons: Memantine [1-amino-3,5-dimethyladamantane] and Flupirtine [2-amino-3-ethoxycarbonylamino-6-(4-fluoro-benzyl-amino)-pyridine maleate]. Both compounds have been found to display a potent cytoprotective effect on neurons treated with the excitatory amino acid NMDA or with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. The NMDA antagonist Memantine, a drug currently used in the therapy of spasticity and Parkinson's disease, prevented the effects of gp120 at micromolar concentrations. Flupirtine was previously found to be a centrally acting, nonopiate analgesic agent which additionally possesses anticonvulsant and muscle-relaxant activity at doses similar to those producing analgesia. The cytoprotective effect of Flupirtine in vitro was significant (above 10 microM). Considering the fact that both Memantine and Flupirtine display almost no clinical side effects, these drugs may prove useful both in preventing primary infection of brain cells with the HIV virus, as well as in treating the neurological disorders often associated with the immunodeficiency syndrome such as AIDS-related dementia.

In the present study is is reported that the methanolic Hypericum extract LI 160 (Jarsin 300) exerts no protective effect against N-methyl-D-aspartate (NMDA-) or gp120- (from the HIV virus) induced cytotoxicity. Moreover, it is established that Hypericum extract causes no activation of arachidonic acid release from neurons activated by gp120; hence it displays no sensitization effect on the NMDA receptor channel. The main outcome of this study is the finding that Hypericum extract causes a 50% inhibition (IC50 value) of serotonin uptake by rat synaptosomes at a concentration of 6.2 microglml. Therefore it is concluded that the antidepressant activity of Hypericum extract is due to an inhibition of serotonin uptake by postsynaptic receptors. Future studies might focus on the effect of Hypericum extract on serotonin binding to neurons, serotonin storage in granules, the rate of synthesis of serotonin, and on the activity of monoamine oxidase.

Previous irradiation could induce changes in the cell-sensitivity to additional cytotoxic agents. In this study we examined whether the sensitivity to additional cytotoxic agents was affected in cells irradiated with multiple fractions of gamma rays if these agents were given at the time when the lesions induced in DNA by radiation have already been repaired. Human cervix carcinoma HeLa cells were irradiated daily with 0.5 Gy of gamma rays five times a week for 6 weeks. When the fractionation regimen was completed, that is when the cells had accumulated the total dose of 15 Gy of gamma rays, the sensitivity of these cells to gamma rays, UV light, cis-dichlorodiammineplatinum (II) (cis-DDP), methotrexate (MTX), and hydroxyurea (HU) was examined and compared to control cells. Results revealed that preirradiated cells did not change sensitivity to gamma rays and UV light, but that they increased the resistance to cis-DDP, and MTX (especially for higher concentrations of MTX), and increased sensitivity to HU (for lower concentrations of HU). The increased resistance to cis-DDP was also measurable up to 30 days after the last dose of gamma rays. The results indicate that preirradiation of HeLa cells with multiple fractions of gamma rays could change their sensitivity to additional cytotoxic agents, and that this is a relatively long-lasting effect. Our results suggest that caution is needed in medical application of radiation combined with chemical treatment.

Der Zusammenhang der paratestikularen Missbildungen mit dem Kryptorchismus stellt ein Problem dar, das erst in den letzten Jahren im Mittelpunkt der Interesse geruckt worden ist. Mit Ausnahme von einigen vereinzelten Fallen, wurden in der bisherigen Literatur nur zwei prospektive Studien veroffentlicht (1,2). Unsere Studie ist eigentlich parallel und unabhangig von der Studie von Heath et al. zustandegekommen.

Two new bromopyrrole alkaloids, damipipecolin (1) and damituricin (2), have been isolated from the Mediterranean sponge Axinella damicornis, and their structures established through spectroscopic methods. Compounds 1 and 2 extend the structural variety of the so far known pyrrole alkaloids; in these compounds, the 4-bromopyrrole 2-carboxylic acid is directly condensed with a non-protein cyclic alpha-amino acid, the (2R, 4R)-trans-4-hydroxypipecolic acid and (2R, 4R)-cis-N,N'-dimethyl-4-hydroxyproline (D-turicine) in 1 and 2, respectively. Compounds 1 and 2 were found to display a modulating effect of the serotonin receptor activity in vitro.

The Mediterranean sponge Axinella verrucosa has been investigated for its alkaloid composition and has been found to produce a complex mixture of bromopyrrole alkaloids. Along with the previously isolated compounds 5-18, four novel alkaloids of this class, compounds 1-4, have been isolated, and their structures established through spectroscopic methods. Compounds 1-4 were found to display neuroprotective activity against the agonists serotonin and glutamate in vitro.

The isolation and characterization of the known pyrrole alkaloid agelongine ( 6 ) and of the new natural product daminin ( 7 ), the bromine-free analogue of 6 , from a specimen of the marine sponge Axinella damicornis is described. Compound 7 showed significant neuroprotective properties. Moreover, for the supply of sufficient material for future medicinal investigations, a short total synthesis of 7 was developed.