The continent bladder: indications and techniques for the continent catheterizable segment

PURPOSE OF REVIEW: Continent catheterizable segments are a substantial part of the urologist's armamentarium for providing bladder drainage. It is used for a myriad of indications, and there are multiple techniques currently used for its formation. Despite refinements in these techniques significant complications still occur, and there is continued advancement and ongoing investigation. This review examines the current status of the continent catheterizable segment with regard to indications for its use, techniques in its formation, discussion of complications, and ongoing and future directions in research. RECENT FINDINGS: The continent catheterizable segment is indicated when it is not feasible to use the urethra for evacuation (e.g. bladder exstrophy, neurogenic bladder, radiation injury, and marked urethral dysfunction) or to facilitate catheterization. Compliance with catheterization and irrigation regimens is essential in patient selection. Multiple methods exist for its formation, either with or without the need for bladder augmentation. Although Mitrofanoff techniques with multiple applications predominate, "hemi" augments with efferent limbs also play a significant role. Stoma placement should be performed to best facilitate catheterization. Complications relating to catheterizable segments mainly pertain to continence, stenosis, and ability to catheterize, with more significant morbidity relating to the bladder augmentation. Ongoing research to develop more physiologic tissue substitutes and less invasive techniques may hopefully be superseded by prevention of the underlying lower urinary tract pathology. SUMMARY: Catheterizable segments allow the patient to control bladder evacuation, and continue to be refined by ongoing investigations in terms of indication and technique, with attendent decreasing morbidity.     

Postoperative mortality after nontraumatic lower extremity amputation in patients with renal insufficiency

Mortality rates after lower extremity amputation are extremely high among dialysis patients. However, the impact of milder degrees of renal insufficiency on death rates after lower extremity amputation has not been carefully examined. In this study, the authors used data from the Department of Veterans Affairs' National Surgical Quality Improvement Program (NSQIP) to measure the association between renal dysfunction and 30-d mortality after nontraumatic amputation adjusted for confounders. The study population consisted of 16,994 patients undergoing their first NSQIP recorded amputation from January 1, 1994 through September 30, 2001. Thirty-five percent of all cohort patients had at least moderate renal insufficiency, and 52% of all postoperative deaths occurred in this group. Postoperative mortality was 9% in patients with moderate renal insufficiency, 15% in patients with severe renal insufficiency, and 16% in dialysis patients, compared with 6% in patients with normal or mildly reduced renal function. Renal insufficiency remained associated with death after adjustment for confounders (adjusted odds ratio [OR] 3.36, 95% confidence interval [CI] 2.75 to 4.10 [dialysis patients]; OR 2.54, CI 2.06 to 3.14 [severe renal insufficiency]; and OR 1.52, CI 1.32 to 1.76 [moderate renal insufficiency]). In conclusion, even moderate renal insufficiency is independently associated with postoperative death after lower extremity amputation. This finding highlights the need for a targeted approach to improving the care of patients with renal insufficiency undergoing lower extremity amputation.     

Limitations in the interpretation of biopsies in patients with penile squamous cell carcinoma

Surgeons often perform small or superficial penile biopsies that are difficult to classify definitely with regard to a benign or malignant nature, and if malignant, cannot always be accurately subclassified. Staging and therapeutic decisions rely on the identification, in these materials, of pathologic parameters related to prognosis. In this study, we evaluated the accuracy and completeness of pathologic information obtained from biopsies of 57 consecutive patients with squamous cell carcinoma (SSC) of the penis, and compared it with the information obtained from penectomies. Diagnostic accuracy was determined by recording discordances of critical factors in biopsies and penectomies. The evaluated parameters were as follows: cancer diagnosis, histologic type, tumor grade, depth of invasion (anatomical levels), and vascular invasion. Histologic subtypes of SCC were the following: usual 37, verruciform 11, mixed 7, pseudohyperplastic 1, and sarcomatoid 1. Grades were 1, 2, and 3 (well, moderately and poorly differentiated). Levels of invasion were lamina propria, corpus spongiosum, and corpus cavernosum in the glans; and lamina propria, dartos, and skin in the foreskin. In 2 patients with well-differentiated tumors a diagnosis of cancer could not be established in biopsy material. In 17 cases (30%) there was a biopsy-penectomy discordance of histologic types, especially of verruciform and mixed carcinomas. Biopsies failed to identify the correct histologic grade in 30% of the cases. A higher grade was usually identified in penectomy specimens. Because biopsies were superficial, the deepest point of invasion could not be determined in 91% of the cases. Vascular invasion was identified in biopsies in only 1 of 8 patients. In summary, biopsies were useful for cancer diagnosis except in 2 differentiated variants of penile squamous cell carcinoma. However, important pathologic parameters related to prognosis were missed on biopsy materials, and they were more accurately evaluated in penectomy specimens. We conclude that clinical and pathologic staging of penile cancer, at least in our material, cannot depend on biopsy information alone. Data from biopsies may be insufficient to make a decision whether to perform a groin dissection, or for prognostic evaluation in those patients in whom other treatment modalities (such as radiotherapy or chemotherapy) are being considered.     

Portable colposcopy in low-resource settings

Screening for cervical dysplasia is an important public health effort worldwide. In unscreened populations, the incidence of cervical cancer ranges between 2 and 4% of the adult female population, whereas less than 0.1% of the screened population of Caucasian women has cervical cancer in the United States. In developing countries, cervical cytology is difficult to implement successfully because of the cost, cultural constraints, limited access to pathology services, etc. Bypassing cytology and going directly to colposcopy has been successfully implemented as a screening strategy for dysplasia in low resource settings. In this article we describe the development and utilization of a portable binocular colposcope that does not require electricity.     

Antithymocyte globulin is associated with complement deposition in cardiac transplant biopsies

Polyclonal antithymocyte globulin preparations contain antibodies with reactivity to endothelial cells. Therefore, we investigated whether treatment with this reagent caused complement deposition in human cardiac transplants. Frozen tissue was available from endomyocardial biopsies of 75 patients, who were transplanted between April 1995 and April 2000. Nine of these patients were converted from cyclosporin A (CsA) to horse antithymocyte globulin (ATGAM) in the first month after transplantation. All of the biopsies were stained by immunofluorescence for C4d as evidence of activation of the classical pathway of complement. In addition, biopsies from patients treated with ATGAM and control patients were stained for deposition of horse immunoglobulin (Ig)G. All nine patients who received ATGAM had deposition of horse IgG and C4d. Two color stains demonstrated that the horse IgG colocalized with the C4d staining. No staining for horse IgG or C4d was evident in biopsies obtained before ATGAM treatment. Likewise, no staining for horse IgG was detected in seven control patients who had C4d staining. Most patients treated with ATGAM had no histologic evidence of rejection, but did have myocyte damage and macrophage infiltration. Thus prophylactic treatment with ATGAM is associated with the deposition of horse IgG and activation of complement in the transplant.     

Novel plant pathogenesis-related protein family involved in food allergy

BACKGROUND: Members belonging to 9 different families of plant pathogenesis-related (PR) proteins have been identified as pollen and food allergens. However, no PR-1 protein, a family widely distributed throughout the plant kingdom, has been involved so far in allergic reactions. On the other hand, melon ranges among the most relevant fruits causing food allergy in some countries, but the majority of its allergens remain still unidentified. OBJECTIVE: We sought to identify melon allergens related to plant PR proteins. METHODS: A serum pool or individual sera from 17 patients with allergy to melon confirmed by means of double-blind, placebo-controlled food challenge were used to detect IgE binding proteins of extracts from melon pulp and juice. Cuc m 3 was isolated from melon juice by reverse-phase HPLC and characterized by means of N-terminal amino acid sequencing of internal peptides, matrix-assisted laser desorption/ionization mass spectrometry analysis, direct and inhibition ELISA assays, and skin prick tests. RESULTS: Cuc m 3 was a minor component of the melon juice, with a molecular weight of 16,097 d and a blocked N-terminus. N-terminal amino acid sequences of 3 different peptides derived from endo-Lys C digestion (overall 41 residues) showed more than 60% of sequence identity with PR-1 proteins from grape and cucumber. Cuc m 3 bound IgE from 12 of 17 sera from patients allergic to melon and inhibited approximately 40% and 70% of the IgE binding to melon pulp and juice extracts, respectively. Positive skin prick test responses to purified Cuc m 3 were found in 2 of 14 allergic patients. CONCLUSION: A new melon allergen belonging to the PR-1 protein family has been isolated and characterized. It is the first evidence of the involvement of this plant protein family in food allergy.     

Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients

Pneumocystis infection in humans was originally described in 1942. The organism was initially thought to be a protozoan, but more recent data suggest that it is more closely related to the fungi. Patients with cellular immune deficiencies are at risk for the development of symptomatic Pneumocystis infection. Populations at risk also include patients with hematologic and nonhematologic malignancies, hematopoietic stem cell transplant recipients, solid-organ recipients, and patients receiving immunosuppressive therapies for connective tissue disorders and vasculitides. Trimethoprim-sulfamethoxazole is the agent of choice for prophylaxis against Pneumocystis unless a clear contraindication is identified. Other options include pentamidine, dapsone, dapsone-pyrimethamine, and atovaquone. The risk for PCP varies based on individual immune defects, regional differences, and immunosuppressive regimens. Prophylactic strategies must be linked to an ongoing assessment of the patient's risk for disease.     

Safe and reliable sound threshold measures with direct vibration of the ossicular chain

OBJECTIVES: The aim of the study was to evaluate the safety and feasibility of piezoelectric malleus vibration audiometer (MVA), which presents micromechanical vibrations to the umbo membranae tympani. STUDY DESIGN: Phase I study performed in a tertiary referral center (University Hospital). METHODS: The coupling rod of the MVA was moved slowly through the outer ear canal toward the eardrum with a micromanipulator. Coupling was completed when the rod tip touched the umbo membranae tympani. Basic audiologic measures of sound threshold obtained with direct stimulation of the malleus are presented. We used MANOVA (multivariate repeated measures ANOVA) to investigate the repeatability of MVA thresholds from one day to the other and when decoupling and retracting the coupling rod 2 mm off the umbo. We also selected the MANOVA to test for unwanted bone-conduction threshold shifts after MVA application. We assessed normality of the data by quantile-quantile plots of the residuals. RESULTS: Twenty-eight male and 10 female subjects with normal hearing, 22.2 to 34.6 years old (median age, 27.2 yr) underwent an examination. Thirty-six subjects underwent MVA, because 2 of the 38 subjects who volunteered for the study have not undergone the procedure due to the external auditory canal anatomy preventing application of the MVA. The results show that it is possible to safely and reliably measure thresholds of direct vibration of the ossicular chain. Using pure tone audiograms, no pure tone bone- and/or air-conduction threshold shifts occurred after the procedure. None of the subjects reported any other ear-related symptoms such as vertigo, tinnitus, or dizziness. Geometric mean vibratory displacements at threshold ranged from 0.55 nm at 250 Hz to 0.03 nm at 6 kHz. MANOVA demonstrated a repeatability of MVA thresholds. CONCLUSION: Malleus vibration audiometry will not allow exact linkage of actual implantable hearing aid. But the present study demonstrates that MVA can provide an audiometric tool for assessing ossicular function and integrity prior to implantation of an electronic hearing amplifier.     

Regression of HPV-positive tumors treated with a new Listeria monocytogenes vaccine

BACKGROUND: Human papillomavirus (HPV) has been implicated in the pathogenesis of 15% to 23% of head and neck squamous cell carcinomas as well as most oropharyngeal carcinomas. The viral oncoproteins E6 and E7 are expressed in HPV-positive tumor cells and therefore provide ideal targets for tumor immunotherapy. Because of its unique ability to induce a cellular immune response, the intracellular bacteria Listeria monocytogenes has been studied as a potential HPV-positive tumor vaccine. OBJECTIVE: To present a new recombinant strain of L monocytogenes that is effective in treating HPV-positive tumors in a murine model. DESIGN: A new recombinant L monocytogenes vaccine, Lm-ActA-E7, was designed by transforming an attenuated Listeria strain with an E7 expression cassette. The cassette consists of the HPV-16 E7 sequence fused to the Listeria protein ActA. The resultant strain of bacteria secretes E7 antigen as a fusion protein with ActA. METHODS: Tumors were established in C57BL/6 mice with a syngeneic HPV-positive cell line prior to treatment with vaccine. INTERVENTION: The Lm-ActA-E7 vaccine was administered intraperitoneally to the mice 5 days after tumors were established. A booster dose was administered 7 days after the first dose. Tumor progression was measured in 2 dimensions periodically after the vaccination. RESULTS: In C57BL/6 mice, the administration of Lm-ActA-E7 caused the complete regression of HPV-positive tumors in 6 of 8 mice tested. A cytotoxic T-lymphocyte assay revealed that administration of the vaccine caused the generation of cytotoxic T cells specific for E7. CONCLUSION: Our results demonstrate the ability of a new Listeria-based vaccine to generate a specific antitumor T-cell response and cause the regression of HPV-positive tumors in a murine model.