Long-term follow-up of total penile reconstruction with sensate osteocutaneous free fibula flap in 18 biological male patients

Surgical reconstruction of the penis is challenging because of the many cosmetic and functional (e.g., sexual intercourse and voiding) requirements that must be addressed. Since the free sensate osteocutaneous fibula flap was first described for total penile reconstruction in 1993 it has been widely accepted, with its advantages and minimal shortcomings. In this article, the authors present the longest follow-up of biologically male patients with free fibular phalloplasties. Since 1994, 18 biologically male patients with total penile losses for various reasons were treated with free sensate osteocutaneous fibula flaps. All patients were included in the study. The ages of the patients ranged between 20 and 26 years (mean, 22.2 years). The average follow-up period was 5.4 years (range, 1 to 9 years). Patient satisfaction was evaluated by a questionnaire regarding both quality of orgasm and daily activities. Conventional radiographic imaging, magnetic resonance imaging, and bone mineral densitometry were performed to evaluate the fate of the bony component of the flap. Also, sensibility was evaluated by bulbocavernous reflex and penile somatosensory evoked potentials testing in nine patients. Six patients married, and five of them had six children. Most patients and their partners reported pleasurable sexual intercourse and orgasm. Conventional radiographs of the fibular bone in neophalluses showed robust, calcified bone structure without any evidence of bone resorption or fracture. The magnetic resonance images showed the cortical substance and spongiosum of the bone marrow, which are characteristic signs of bone viability. After intravenous injection of gadolinium, the neophallus bone showed uptake of contrast medium. Viability of neophallus bone was shown even at 9-year follow-up (the longest follow-up in the literature). Dual energy x-ray absorptiometry measurements of the penile bone grafts showed that fibular components in the penis had bone mineral density values that were close to but lower than those of intact fibula in the same subjects. These results were considered as evidence of viability of bone grafts. Neural integrity was found between the nerves of the neophallus and the residual penile bodies by both bulbocavernous reflex and penile somatosensory evoked potentials tests. In conclusion, free sensate fibula flap phalloplasty provides the cosmetic and functional requirements that an ideal penis should have. All results put an end to the discussion that the fibular component of the neophallus could resorb. Constitution of neural integrity is important in terms of pleasurable sexual intercourse. The authors believe the free sensate osteocutaneous fibula flap should be considered as the standard in penile reconstruction.     

Experimental studies on bacterial product cantastim derived from Pseudomonas aeruginosa. VI. Protection in tolerant mice

Endotoxin tolerance is defined as a hyporesponsiveness state to a second stimulation with lipopolysaccharide (LPS). This refractory state is primarily associated with an attenuated cytokine production. Whether this down-regulation of cytokine production results in an increased susceptibility to infection remains a matter of controversy. The aim of this study was to investigate the resistance of tolerant mice to a subsequent bacterial infection and the role of bacterial immunomodulator CANTASTIM (CS) in this experimental model. We have shown that the LPS-tolerant mice (intraperitoneally inoculated with LPS Salmonella typhimurium 10 microg/mouse, daily for two days) were protected against a challenge with Pseudomonas aeruginosa (LD 100) administered 24 h later. On the contrary, when the animals were challenged 1 h after the last LPS injection, they did not survive. However if these animals were pre-treated with CS 3 days before LPS treatment, they became resistant to a subsequent bacterial challenge. More interestingly, if the treatment with LPS was substituted with CS (same schedule, route of administration and doses) there was a significant increase in the survival of mice challenged with Pseudomonas aeruginosa after either 1 h or 24 h. In this case, the increase in the rate of survival was correlated with an enhanced production of IL-10 in the peritoneal cavities of CS treated mice as compared to LPS treated mice.     

Complementary expression patterns of retinoid acid-synthesizing and -metabolizing enzymes in pre-natal mouse inner ear structures

Retinoic acid (RA) plays a pivotal role in patterning and differentiation of the embryonic inner ear. Despite its documented effects during embryonic development, the cellular sites that synthesize or metabolize RA in the inner ear have yet to be determined. Here we describe the distribution of three synthesizing enzymes, retinaldehyde dehydrogenases 1, 2 and 3 (RALDH1, RALDH2 and RALDH3) and two catabolizing enzymes (CYP26A1 and CYP26B1) in the mouse inner ear at embryonic day 18.5 when active cell differentiation is underway. Two detection methods, radioactive and non-radioactive in situ hybridization, were employed to elucidate the tissue distribution and cellular localization of these enzymes, respectively. All of the five enzymes examined, with the exception of CYP26A1, were expressed in both vestibular and cochlear end organs. While expression of the three RALDHs was observed in various cell types, CYP26B1 expression was found only in supporting cells of the vestibular and cochlear end organs. In the cochlea, expression domains of RALDH1-3 and CYP26B1 were complementary to one another. These results reveal specific tissue- and cellular expression patterns of RA synthesizing and catabolizing enzymes in the pre-natal inner ear, and suggest that a precise control of RA concentrations in various cell types of the inner ear is achieved by the balance between RALDHs and CYP26B1 activities.     

A review of 35 cases of asymmetric crying facies

A review of 35 cases of asymmetric crying facies: Congenital asymmetric crying facies (ACF) is caused by congenital hypoplasia or agenesis of the depressor anguli oris muscle (DAOM) on one side of the mouth. It is well known that this anomaly is frequently associated with cardiovascular, head and neck, musculoskeletal, respiratory, gastrointestinal, central nervous system, and genitourinary anomalies. In this article we report 35 ACF patients (28 children and 7 adults) and found additional abnormalities in 16 of them (i.e. 45%). The abnormalities were cerebral and cerebellar atrophy, mega-cisterna magna, mental motor retardation, convulsions, corpus callosum dysgenesis, cranial bone defect, dermoid cyst, spina bifida occulta, hypertelorism, micrognatia, retrognatia, hemangioma on the lower lip, short frenulum, cleft palate, low-set ears, preauricular tag, mild facial hypoplasia, sternal cleft, congenital heart defect, renal hypoplasia, vesicoureteral reflux, hypertrophic osteoarthropathy, congenital joint contractures, congenital hip dislocation, polydactyly, and umbilical and inguinal hernia. Besides these, one infant was born to a diabetic mother, and had atrial septal defect and the four other children had 4p deletion, Klinefelter syndrome, isolated CD4 deficiency and Treacher-Collins like facial appearance, respectively Although many of these abnormalities were reported in association with ACF, cerebellar atrophy, sternal cleft, cranial bone defect, infant of diabetic mother, 4p deletion, Klinefelter syndrome, isolated CD4 deficiency and Treacher-Collins like facial appearance were not previously published.     

Effect of regular training on plasma thiols,malondialdehyde and carnitine concentrations in young soccer players

Physical activity is known to induce oxidative stress in individuals subjected to intense exercise. Contrarily, there are enzymatic and nonenzymatic defence systems against oxygen radicals in aerobic organisms. Sulphydryl groups such as thiol and glutathione (GSH) can be given as an example to non-enzymatic low molecular weight antioxidants. Carnitine may be related to the performance enhancement in high intensity intermittent exercises and might probably improve the aerobic capacity by stimulating lipid oxidation in muscle cells during long term exercise. But, the effects caused by this supplement during physical activity have not been fully described in the literature. The aim of the study was to compare plasma thiols (PSH), malondialdehyde (MDA) and carnitine levels and maximal oxygen uptake (VO2(max)) of the soccers under regular training with the values of the healthy controls. Our results demonstrates that soccers seem to be under less oxidative stress, as their MDA levels were significantly lower (P < 0.001) when compared with the control group while their PSH levels were significantly elevated (P < 0.001), during resting condition. In addition, the plasma carnitine concentrations of the soccer group yields lower values while the VO2(max) yields a higher value when compared with the control group. The differences between the soccer and the control groups are significant (for both, P < 0.001). The present research reveals the fact that regular soccer training shows beneficial effect on decreasing of lipid peroxidation levels. Furthermore; the sportsmen who are under intense training programs have low plasma carnitine values which do not cause negative effect on their sportive performance.     

Acute effect of hemodialysis on serum levels of the proinflammatory cytokines

Chronic inflammation is a common feature of end-stage renal disease, which carries a heightened risk of atherosclerosis and other co-morbid conditions. Dialysis treatment per se can bring additional risk factors for inflammation, such as increased risk of local graft and fistula infections, impure dialysate or bio-incompatible membranes. Our study was designed to determine whether a hemodialysis session leads to an acute substantial alteration in the plasma levels of the proinflammatory cytokines interleukin (IL)-6, IL-1beta and tumor necrosis factor (TNF)-alpha, the T-lymphocyte activation factor soluble IL-2 receptor (sIL-2R), and an inflammation mediator and chemotactic granulocyte factor, IL-8, in end-stage renal disease patients receiving chronic intermittent HD. In this study, 21 (12 male/nine female) patients undergoing chronic hemodialysis were enrolled. The acute effect of a hemodialysis session on serum cytokine concentrations was assessed by comparison of pre-hemodialysis and post-hemodialysis determinations. Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha levels were determined with chemiluminescence enzyme immunometric assays. A significant difference was not observed for IL-1beta, IL-6, TNF-alpha, and sIL-2R concentrations in pre-hemodialysis and post-hemodialysis specimens (p>0.05). Serum median (25th-75th percentiles) IL-8 concentration was 69.4 (34.9-110.3) pg/ml before hemodialysis, and decreased to 31.5 (18.0-78.8) pg/ml following hemodialysis (p: 0.006). Clearance of IL-8 increased by 0.47+/-0.08 pg/ml for each unit increase in pre-dialysis IL-8 (p<0.001) and decreased by 5.63+/-2.59 pg/ml for each unit increase in pre-dialysis urea mmol/l (p<0.05). In conclusion, the results of our study demonstrate that a hemodialysis session markedly decreases IL-8 concentration, which is significantly affected by pre-dialysis concentrations, indicating that removal of IL-8 is a concentration gradient-dependent action, but does not change the serum levels of IL-1beta, sIL-2R, IL-6, and TNF-alpha, underlining importance of the structural characteristics of the molecules.