Correction of penile curvature using the 16-dot plication technique: a review of 132 patients

PURPOSE: We review the results of 132 cases of congenital and acquired penile curvature corrected with our 16 or 24-dot, minimal tension technique using multiple parallel plications performed under papaverine induced erection. MATERIALS AND METHODS: Chart and telephone interviews were conducted on 132 consecutive patients 16 to 79 years old who underwent penile plication between December 1995 and November 2000. Patient data as well as outcomes were analyzed. RESULTS: We were unable to contact 8 patients. Of the patients 16 had congenital penile curvature, including 4 in whom the Nesbit procedure performed elsewhere had failed, and 116 had Peyronie's disease, including 8 in whom a previous Nesbit procedure had failed. Preoperative complaints included persistent penile pain with erection for more than 1 year in 15 of 132 cases, difficult intercourse or partner discomfort in 106 and poor self-image in 11. Curvature ranged from 30 to 120 degrees. Erections were evaluated preoperatively with duplex ultrasound after intracavernous injection and self-stimulation. Of the patients 63% had good erections, 25% moderate erections requiring sildenafil and 12% poor erections requiring injection therapy. Foreskin edema necessitating subsequent circumcision and an organized hematoma requiring evacuation occurred in 1 case each. At 6 months 93% of patients reported straight erections and 7% reported almost straight but acceptable erections. Recurrence of curvature was reported by 15% of patients at a mean of 2.6 years of followup. Four patients reported worsening of erectile function after the procedure. CONCLUSIONS: Penile plication is a simple, safe method to correct congenital and acquired penile curvature. Using a minimal tension parallel plication technique, excellent durable results can be attained. This simplified repair avoids the neurovascular bundles and has a minimal to no detrimental affect on erectile function. Preoperative counseling must be given regarding penile shortening and the palpable small bumps from the nonabsorbable sutures.     

Long-term survival of autotransplanted major pelvic ganglion in the corpus cavernosum of adult rats

PURPOSE: Neurogenic impotence is a common complication after radical pelvic surgery, irradiation or perineal trauma. Neuronal transplantation is a new frontier for treating neurological disorders. We investigated whether the major pelvic ganglion can survive and become functional after being implanted into the corpus cavernosum in adult rats. MATERIALS AND METHODS: Adult male rats (13) were divided into 3 groups and sacrificed at 3 time points, namely 30 (4), 60 (5) and 90 (4) days. All rats underwent excision of the right major pelvic ganglion and left cavernous nerve. The right ganglion was implanted into the right crus of the penis. Electrostimulation was applied to the left major pelvic ganglion and cavernous nerve (1.5 mA.) and right crus (10 mA.) at sacrifice. The crural region and left ganglion were then excised for immunostaining of neuronal nitric oxide synthase (nNOS), protein gene product 9.5 and growth associated protein 43. Image analysis was used to calculate the area stained in pixels. Electron microscopy of the implanted area was performed to assess neuronal survival. RESULTS: Although the degree varied, all neuronal implants survived after transplantation. The response to electrostimulation was insufficient to produce erection. No difference was noted among the areas of nNOS staining when specimens from the 3 time points were compared. The area of expression of nNOS, protein gene product 9.5 and growth associated protein 43 was larger in the implanted area than in the surrounding cavernous tissue. Under electron microscopy most surviving implants showed normal ultrastructure, although areas of fibrotic replacement were seen in several implants. CONCLUSIONS: Our results show that the autotransplanted major pelvic ganglion expresses nNOS, protein gene product 9.5 and growth associated protein 43, and survived up to 90 days after implantation into the corpus cavernosum. Further studies with fetal neuronal tissue seem warranted.     

Long-term effect of ovariectomy and simulated birth trauma on the lower urinary tract of female rats

PURPOSE: Using an animal model we studied the long-term effects of ovariectomy and simulated birth trauma in the development of apoptosis as well as the urodynamic, histological and ultrastructural findings 9 months after such procedures. MATERIALS AND METHODS: A total of 24 pregnant Sprague-Dawley female rats were used. Immediately after delivery 14 animals underwent vaginal ballooning and ovariectomy, while the remaining 10 served as controls. At 9 months the animals underwent urodynamic evaluation, which included the urethral pressure profile. The rats were then sacrificed and urogenital tissue was obtained for immunostaining using terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling, histomorphometry evaluation and electron microscopy. RESULTS: Immunostaining demonstrated a significant increase in the apoptotic index in the urethra of castrated/ballooning rats with a predominance in the submucosa layer. Maximum urethral closure pressure was significantly lower in that group, although there was no correlation of apoptosis with maximum urethral closure pressure measurement. Urodynamic evaluation revealed only discrete alterations in cystometric parameters. Morphometric evaluation showed increased connective tissue in the vagina. Electron microscopy of urethral smooth muscle demonstrated altered cellular shape, increased intercellular space with collagen deposition and some degeneration of the mitochondria. CONCLUSIONS: Apoptosis in the urethra occurs 9 months after castration and simulated birth trauma. However, this finding was not seen in the muscle layers or in other urogenital tissues. Some ultrastructural changes also occurred that may explain some symptoms that women have after vaginal childbirth and menopause.     

Reactions of purines-containing butenolides with L-cysteine or N-acetyl-L-cysteine as model biological nucleophiles: a potent mechanism-based inhibitor of ribonucleotide reductase caused apoptosis in breast carcinoma MCF7 cells

Thiols are the most reactive nucleophilic reagents among the biological models investigated. The reactivity of butenolides 1a-c, 2-4, and 6-8 toward L-cysteine, a model biological nucleophile, was studied spectrophotometrically. The rates of the reactions were measured and correlated with antitumour activity of these molecules. N-Acetylcysteine addition product 5, resulting from the treatment of butenolide 4 with glutathione precursor, N-acetyl-L-cysteine, was isolated. Unlike purine-containing gamma-(Z)-ethylidene-2,3-dimethoxybutenolides 1a-c, 4, 6, and 7, adduct 5 and butenolides 10-12 did not exhibit inhibitory activity against murine leukemias (L1210 and P388), breast carcinoma (MCF7), and human T-lymphoblasts (Molt4/C8 and CEM/0) cell lines. As such, the biological activity of purine-containing butenolides can be attributed to their adenine moiety as a recognition site as well as their reactivity towards the cysteine residues of functional proteins forming covalent bond via reverse Michael type addition. Adenine-containing phosphonothioanhydride derivative 8 was also synthesised. Its reaction with N-acetyl-L-cysteine produced N,S-diacetylcysteine and thiophosphonate 9. Compound 9 did not exhibit anticancer activity; yet its precursor 8 displayed the most pronounced inhibition on all the examined malignant tumour cell lines. In the presence of L-cysteine, cytotoxicity of 4 and 8 was decreased, whereas glutathione addition more influenced on the cytotoxicity of 8. It was found that adenine-containing phosphonothioanhydride 8 functions as a significant irreversible inactivator of the Escherichia coli ribonucleoside diphosphate reductase. After treatment of MCF7 cells with compound 8, fluorescence microscopy demonstrated the presence of nucleus shrinkage or segmentation. This apoptotic morphology, however, was not pronounced in the presence of glutathione or dithiotheritol.     

Cellular tumor vaccines administered after T cell-depleted allogeneic bone marrow transplantation induce effective anti-tumor immune responses

In allogeneic hematopoietic stem cell (HSC) transplantation, graft vs. tumor (GVT) activity contributes to the cancer cure. It is closely associated with graft vs. host disease (GVHD), an immune response initiated by transplanted donor T-cell responses against host minor histocompatibility antigens (mHAgs). GVHD is prevented by T-cell depletion of the donor graft, but T-cell depletion also abrogates curative GVT. We wished to test the hypothesis that cellular tumor vaccines administered after T cell-depleted HSC transplant can induce significant GVT effects, despite the absence of transplanted mature donor T cells. In this investigation, a murine model of major histocompatibility complex (MHC)-matched, mHAg-mismatched allogeneic HSC transplant was studied. T cell-depleted or normal T cell-containing grafts were given to myeloablated recipients. Following reconstitution the recipients were vaccinated with tumor vaccines. GVT responses were measured in vitro by T-cell function assays and flow cytometry, and in vivo by tumor burden or survival. Post-transplant tumor vaccines induced effective anti-tumor responses in recipients of T cell-depleted transplants, producing cytolytic and cytokine responses, reduced tumor burden and prolonged survival. Recipients of T cell-depleted transplants that still have significant thymic function may be suitable subjects for post-transplant vaccine therapy.     

Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

Purpose The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [¹²³I]FP-CIT.Methods [¹²³I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [¹²³I]FP-CIT scans with bone metabolism and perfusion scans obtained with ^99mTc-DPD and ^99mTc-tetrofosmin, respectively. As these tracers do not pass the blood–brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [¹²³I]FP-CIT scans with images of brain perfusion obtained with ^99mTc-HMPAO.Results Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V₃) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (t test, two-tailed, p<0.0001). Cortical V₃ values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [¹²³I]FP-CIT accumulation.Conclusion The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [¹²³I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinsons and Huntingtons disease, may be feasible using SPECT radioligands and small animal imaging systems.     

Neonatal disseminated methicillin-resistant Staphylococcus aureus presenting as orbital cellulitis

Orbital cellulitis and abscess are known complications of ethmoiditis in children, but they are very rare in the newborn. The authors report a case of orbital abscess caused by methicillin-resistant Staphylococcus aureus (MRSA) in a four-week-old neonate born four weeks prematurely.     

Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background  

HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation.     

In vivo feasibility of image-guided transvaginal focused ultrasound therapy for the treatment of intracavitary fibroids

OBJECTIVE: To determine the feasibility of uterine tissue ablation in vivo using a transvaginal focused ultrasound applicator guided by ultrasound imaging. DESIGN: Randomized in vivo animal study. SETTING: Academic research environment. ANIMAL(S): Healthy anesthetized sheep. INTERVENTION(S): Uterine treatment location was determined using a computerized targeting system. Five sonications 10 seconds in duration and averaging 2,000 W/cm(2) of focal ultrasound intensity were applied in each animal's uterus. Animals were euthanized either immediately or 2, 7, or 30 days post-treatment. MAIN OUTCOME MEASURE(S): Gross and microscopic analysis of the dissected uterus was used to quantitatively and qualitatively determine the ablated region and treatment side effects. RESULT(S): Treatments resulted in coagulative necrosis. Histopathological analysis showed that over 7 days, inflammatory cells appeared and smooth muscle bundles regenerated. By day 30, treated tissues healed and scar tissue formed. None of the animals showed abnormal behavior or medical problems. Complications in three animals were damage to the vaginal wall and colon, possibly due to inadequate applicator cooling and an empty bladder during treatment. CONCLUSION(S): Transvaginal image-guided high-intensity focused ultrasound has potential for treating uterine fibroids. Further safety testing of this treatment will prepare it for human use.     

The channel architecture of aquaporin 0 at a 2.2-A resolution

We determined the x-ray structure of bovine aquaporin 0 (AQP0) to a resolution of 2.2 A. The structure of this eukaryotic, integral membrane protein suggests that the selectivity of AQP0 for water transport is based on the identity and location of signature amino acid residues that are hallmarks of the water-selective arm of the AQP family of proteins. Furthermore, the channel lumen is narrowed only by two, quasi-2-fold related tyrosine side chains that might account for reduced water conductance relative to other AQPs. The channel is functionally open to the passage of water because there are eight discreet water molecules within the channel. Comparison of this structure with the recent electron-diffraction structure of the junctional form of sheep AQP0 at pH 6.0 that was interpreted as closed shows no global change in the structure of AQP0 and only small changes in side-chain positions. We observed no structural change to the channel or the molecule as a whole at pH 10, which could be interpreted as the postulated pH-gating mechanism of AQP0-mediated water transport at pH >6.5. Contrary to the electron-diffraction structure, the comparison shows no evidence of channel gating induced by association of the extracellular domains of AQP0 at pH 6.0. Our structure aids the analysis of the interaction of the extracellular domains and the possibility of a cell-cell adhesion role for AQP0. In addition, our structure illustrates the basis for formation of certain types of cataracts that are the result of mutations.