Ureteral metal stents: a tale or a tool?

There are four types of ureteral metal stents: self expandable, balloon expandable, covered, and thermoexpandable shape-memory. Insertion of metal stents requires expertise with transurethral and percutaneous techniques. The stricture is traversed with the aid of a guidewire via a percutaneous nephrostomy, and the stenotic segment is dilated using a high-pressure balloon catheter. The stent is then inserted over the guidewire, such that the upper end bypasses the obstruction by at least 3 to 4 cm, while the lower end extends intravesically for 0.5 to 1 cm from the ureteral orifice. If necessary, two or more stents are placed in sequence, overlapping by at least 2 to 3 cm. Metal stents were initially used for the relief of end-stage malignant disease, and their role in the treatment of benign ureteral strictures is still undefined. Patients often complain of abdominal discomfort and mild pain after stent insertion, which soon resolve spontaneously. Hematuria usually stops after a few days and does not necessitate any treatment. Mild urothelial hyperplasia in the stent lumen is common but usually regresses after 4 to 6 weeks. Many authors suggest the use of a double-pigtail catheter for the first 4 to 6 weeks to avoid narrowing of the ureteral lumen. The influence of stents on ureteral peristalsis is a major but poorly documented issue. Encrustation is a significant problem that needs to be addressed. The characteristics of both the patient and the stent influence its likelihood. Migration of coated metal stents was seen in 81% of patients at our center. Virtual endoscopy has recently been introduced as a tool for the follow-up of patients with stented ureters. Further design development is necessary to obtain the ideal ureteral metal stent. In a recent study in female pigs, paclitaxel-eluting metal stents engendered less inflammation and hyperplasia of the surrounding tissues.     

How have new sterilization techniques and new forms of polyethylene influenced wear in total joint replacement?

Polyethylene has undergone many changes over the past several decades, including changes in consolidation processes, resin types, sterilization methods, packaging, and the extent of cross-linking. We believe that new sterilization techniques and forms of polyethylene have generally improved wear performance. Polyethylene sterilized without the use of radiation has been shown to have relatively high rates of wear in vivo. Ram-extruded polyethylene sterilized via gamma irradiation in air has been the most commonly used bearing material in the past several decades. Recently, components molded and gamma-sterilized without oxygen as well as highly cross-linked material have found increased clinical use. Exposure of polyethylene to radiation, either to sterilize it or to intentionally cross-link it, has been shown to improve the wear performance of the material. Newer second-generation methods of cross-linking polyethylene include the use of vitamin E, which quenches free radicals and demonstrates promise in providing low wear and desirable mechanical properties.     

Alternative filler materials and new implant designs: what's available and what's on the horizon?

Despite ample evidence that silicone gel-filled implants do not cause systemic illness, they are still not available in the United States for widespread use. At this point, saline-filled implants are widely available for use, and assuming favorable outcomes of the relevant silicone studies, some forms of silicone gel-filled implants could be approved by the FDA and be available as soon as 2003. Other products under preliminary consideration by the FDA for eventual studies include the 150 series and the cohesive silicone gel-filled 410 series by McGhan, and the NovaGold implant by NovaMed. Assuming favorable study results, one or more could be approved by the FDA by the year 2004. Any products not yet submitted to the FDA for review of study designs by this time are not likely to be available in the United States in the next 4 or 5 years.     

Sole stenting of large and giant intracranial aneurysms with self-expanding intracranial stents—limits and complications

Background  

Intracranial aneurysms may be difficult for endovascular treatment due to size, fusiform shape, or wide neck. In such patients, intracranial stents are used to support the coils in the aneurysm sac, or they may be used as a sole stenting technique to divert the blood flow without coils. The aim of this paper is to contribute to the existing data by reviewing the risks of sole stenting of large and giant aneurysms.     

Ureteral Stenosis After Renal Transplantation—A Single-Center 10-Year Experience

Background

Kidney transplantation (KT) is the definitive treatment for ESRD. Ureteral stenosis (US) is one of the most common urologic complications and has been reported in 2.6%–15% of KTs.

Osteogenesis imperfecta in children and adolescents—new developments in diagnosis and treatment

Osteogenesis imperfecta (OI) is the most prevalent heritable bone fragility disorder in children. It has been known for three decades that the majority of individuals with OI have mutations in COL1A1 or COL1A2, the two genes coding for collagen type I alpha chains, but in the past 10 years defects in at least 17 other genes have been linked to OI. Almost all individuals with a typical OI phenotype have a mutation in one of the currently known genes. Regarding medical treatment, intravenous bisphosphonate therapy is the most widely used medical approach. This has a marked effect on vertebra in growing children and can lead to vertebral reshaping after compression fractures, but there is little effect of bisphosphonate therapy on the development of scoliosis. Bisphosphonate treatment decreases long-bone fracture rates, but such fractures are still frequent. Newer medications with anti-resorptive and bone anabolic action are being investigated in an attempt to improve on the efficacy of bisphosphonates but the safety and efficacy of these new approaches in children with OI is not yet established.     

Pathophysiology,diagnosis, and treatment of methylmalonic aciduria—recent advances and new challenges

Classical methylmalonic aciduria is a relatively rare inborn error of branched-chain amino acid metabolism, occurring in 1:50,000 to 1:80,000 newborns. Three decades after its recognition, major progress has been made in survival and prevention of neurological sequelae in affected children, if the diagnosis is made early and treatment and follow-up care are meticulous. Therapy consists of a specially formulated protein diet, carnitine supplementation, and vigorous emergency treatment during intercurrent illnesses aimed at preventing the development of catabolism. Recently the clinician has been challenged by partially unexpected long-term complications. These include chronic neurological symptoms, specifically an extrapyramidal movement disorder caused by progressive destruction of the basal ganglia, which are similar to those observed in other organic acid disorders, such as propionic aciduria or glutaric aciduria type I. Unexpected and unique is the development of chronic renal failure in a major subset of patients. As the pathophysiological basis of renal failure is still obscure, no causative treatment is available and hemodialysis may become necessary. Experience with transplantation of liver, kidney, or kidney and liver is very limited and allows as yet no conclusions. Interdisciplinary research efforts in this field should reveal new pathophysiological links and hopefully provide additional therapeutic approaches.     

KTP laser and nitinol alloy stents: Are they compatible?

BACKGROUND/OBJECTIVE: Nitinol alloy stents are in frequent use in recanalizing malignant airway stenoses. Potassium titanyl phosphate (KTP) is one of the lasers of choice in removal of obstructing airway lesions. There is a paucity of research regarding the safety of these advances working together. STUDY DESIGN/MATERIALS AND METHODS: In vitro study involving direct contact application of KTP laser with nitinol alloy stents under microscope guidance in varying gaseous environments. RESULTS: Stent damage can occur once power settings exceed one watt. Complete stent destruction occurs regardless of gaseous environment at a mere three watts of power. CONCLUSIONS: Our results suggest that KTP laser is unsafe to use in the presence of a nitinol alloy stent, regardless of the gaseous environment.     

Autophagy Regulates TGF-β Expression and Suppresses Kidney Fibrosis Induced by Unilateral Ureteral Obstruction

Autophagy is an evolutionarily conserved process that cells use to degrade and recycle cellular proteins and remove damaged organelles. During the past decade, there has been a growing interest in defining the basic cellular mechanism of autophagy and its roles in health and disease. However, the functional role of autophagy in kidney fibrosis remains poorly understood. Here, using GFP-LC3 transgenic mice, we show that autophagy is induced in renal tubular epithelial cells (RTECs) of obstructed kidneys after unilateral ureteral obstruction (UUO). Deletion of LC3B (LC3^−/− mice) resulted in increased collagen deposition and increased mature profibrotic factor TGF-β levels in obstructed kidneys. Beclin 1 heterozygous (beclin 1^+/−) mice also displayed increased collagen deposition in the obstructed kidneys after UUO. We also show that TGF-β1 induces autophagy in primary mouse RTECs and human renal proximal tubular epithelial (HK-2) cells. LC3 deficiency resulted in increased levels of mature TGF-β in primary RTECs. Under conditions of TGF-β1 stimulation and autoinduction, inhibition of autolysosomal protein degradation by bafilomycin A1 increased mature TGF-β protein levels without alterations in TGF-β1 mRNA. These data suggest a novel intracellular mechanism by which mature TGF-β1 protein levels may be regulated in RTECs through autophagic degradation, which suppresses kidney fibrosis induced by UUO. The dual functions of TGF-β1, as an inducer of TGF-β1 autoinduction and an inducer of autophagy and TGF-β degradation, underscore the multifunctionality of TGF-β1.In the kidney, fibrosis is responsible for chronic progressive kidney failure, and the prevalence of CKD is increasing worldwide.^1,2 Extracellular matrix (ECM) protein production and progressive accumulation are hallmarks of renal tubulointerstitial fibrosis in progressive kidney disease. Collagens are the main components of the ECM in the kidney, and type I collagen (Col-I) is the major type associated with disease states.^3,4 The cellular mechanisms that facilitate tubulointerstitial fibrosis after injury remain incompletely defined. Recent lineage tracing or genetic fate mapping studies have strongly challenged the theory that renal tubular epithelial cells (RTECs) traverse the tubular basement membrane to become myofibroblasts in a process of epithelial-to-mesenchymal transition (EMT), but rather, that interstitial pericytes/perivascular fibroblasts are the myofibroblast progenitor cells.^5–7 It also has been proposed that profibrotic factors, such as TGF-β1, are upregulated in the tubular interstitial area on injury, leading to kidney fibrosis.⁸ TGF-β1 induces production of ECM proteins, including fibronectin and collagens, and inhibits degradation of ECM proteins mainly by matrix metalloproteinases.^9–11 Given the recent evidence that casts doubts about the role of EMT in vivo, how RTECs contribute to the development of renal tubulointerstitial fibrosis is not entirely clear.TGF-β is synthesized as a single polypeptide precursor that includes a preregion signal peptide, which is removed by proteolytic cleavage, and pro–TGF-β, containing a proregion called the latency-associated peptide and a mature TGF-β, and it converts to homodimeric pro–TGF-β through disulfide bonds.¹² After cleavage by proprotein convertases, such as furin, latency-associated peptide remains noncovalently associated with the dimeric form of mature TGF-β as the small latent complex (SLC).¹³ SLC formation occurs in the Golgi apparatus, and mature TGF-β is secreted as part of SLC and associated with latent TGF-β–binding protein to form TGF-β large latent complex, which interacts with ECM. On stimulus, the dimeric form of mature TGF-β is dissociated from large latent complex and becomes the bioactive mature TGF-β ligand, which can then bind TGF-β receptors to trigger downstream Smad-dependent or -independent signaling pathways.^12,13 Thus, the availability of mature TGF-β is the limiting factor of TGF-β activity and not TGF-β synthesis per se, because the body generates more pro–TGF-β than necessary. Whereas TGF-β/TGF-β receptor downstream signaling pathways have been extensively investigated, the regulation of TGF-β maturation and bioavailability has not been well studied but may serve as an important target for fibrotic diseases that alter TGF-β signaling.Macroautophagy, hereafter referred to as autophagy, is a fundamental cellular homeostatic process that cells use to degrade and recycle cellular proteins and remove damaged organelles. The process of autophagy involves the formation of double membrane–bound vesicles called autophagosomes that envelop and sequester cytoplasmic components, including macromolecular aggregates and cellular organelles, for bulk degradation by a lysosomal degradative pathway.¹⁴ Autophagy can be induced in response to either intracellular or extracellular factors, such as amino acid or growth factor deprivation, hypoxia, low cellular energy state, endoplasmic reticulum stress or oxidative stress, organelle damage, and pathogen infection.^15–22 To date, over 30 genes involved in autophagy have been identified in yeast, and they have been termed autophagy-related genes (Atgs). The mammalian ortholog of Atg8 is comprised of a family of proteins known as microtubule-associated protein 1 light chain 3 (LC3) that functions as a structural component in the formation of autophagosomes.²³ LC3B (herein referred to as LC3) is the best characterized form and the most widely used as an autophagic marker. The conversion of the cytosolic form of LC3 (LC3-I) to lipidated form (LC3-II) indicates autophagosome formation. In contrast to LC3, Beclin 1, encoded by the beclin 1 gene, is the mammalian ortholog of yeast Atg6 that is required for the initiation of autophagy through its interaction with Vps34. Homozygous deletion of beclin 1 (beclin 1^−/−) exhibits early embryonic lethality, whereas heterozygous deletion (beclin 1^+/−) results in increased incidence of spontaneous tumorigenesis, abnormal proliferation of mammary epithelial cells and germinal center B lymphocytes, and increased susceptibility to neurodegeneration.^24–27We previously reported that autophagy promotes intracellular degradation of Col-I induced by TGF-β1 in glomerular mesangial cells.²⁸ In the present study, we explored the functional role of autophagy in an in vivo model of progressive kidney fibrosis induced by unilateral ureteral obstruction (UUO) in autophagy-deficient LC3 null (LC3^−/−) and heterozygous (beclin 1^+/−) mice and green fluorescent protein (GFP)-LC3 transgenic mice. We also performed functional studies in primary cultured mouse RTECs and human renal proximal tubular epithelial (HK-2) cells. We hypothesized that induction of autophagy in RTECs promotes TGF-β degradation and thereby reduces TGF-β secretion and suppresses development of kidney fibrosis.     

Angioplasty and stents in coronary artery disease: a systematic review and meta‐analysis

Objectives—To undertake a systematic review of the clinical effectiveness of routine percutaneous transluminal coronary angioplasty (PTCA) plus stenting vs PTCA alone.

Data sources—MEDLINE; EMBASE; Science Citation Index; The Cochrane Library; cardiovascular journals and conference proceedings; Internet resources (including industry supported web pages); and reference lists of included studies and relevant reviews.

Review methods—Study selection included published and unpublished randomized controlled trials (RCTs) comparing the use of coronary stents to PTCA. Outcome measures assessed included death, acute myocardial infarction (AMI), event rate (such as major cardiac adverse events (MACE) or other composite measures), and binary restenosis (BR). Data extraction and quality assessment were conducted according to internationally recognized methods. Data synthesis included meta‐analysis of assessed outcomes, reported as odds ratios (ORs).

Results—Fifty RCTs involving 16?500 patients met the inclusion criteria (39 full articles, 11 abstracts). Of these, 23 studies compared stenting with PTCA in patients with non‐specific coronary artery disease (CAD), 11 compared stents with PTCA following AMI, 8 included patients with small coronary arteries and 8 included patients whose vessels had chronic total occlusion. There were no differences in rates of death or AMI. There were reductions in the rates of MACE (death, AMI or revascularization) with stents compared to PTCA (at 6 months, for non‐specific group OR: 1.64, 95% CI 1.44–1.87; for AMI group OR: 2.36, 95% CI 1.92–2.89; for small vessel group OR: 1.38, 95% CI 1.10–1.74; at 12 months, for non‐specific group OR: 1.31, 95% CI 1.11–1.55; for AMI OR: 2.26, 95% CI 1.47–3.46). Reporting of combined major adverse cardiac events was inconsistent across studies. Most events were revascularizations that may have been partly driven by protocol‐required angiograms. Stents reduced BR rates at angiogram at 6 months compared to PTCA in all groups.

Conclusion—We found no differences in mortality or AMI, but the studies were not powered to identify changes in these endpoints. Coronary stenting is associated with reduced restenosis and combined adverse cardiac events, primarily revascularizations. However, the frequency of revascularization may have been distorted by protocol‐dictated angiography.     

Safety and Efficacy of Ureteroscopic Lithotripsy for Ureteral Calculi Under Sedoanalgesia – A Prospective Study

Objective: To establish the safety and efficacy of ureteroscopic lithotripsy (URSL) under sedoanalgesia. Patients and methods: This study was conducted at Department of Urology (Banaras Hindu University, India) among 124 patients with ureteral stones, between July 2000 and August 2003. Majority of the patients (59.68%) presented with lower ureteric calculi, 24.19% presented with upper ureteric calculi and 16.13% had middle ureteric calculi. All patients were given injection diclofenac sodium (75 mg) promethazine hydrochloride (12.5 mg) deep intramuscular 30 minutes the before procedure. Injection midazolam 0.03 mg/kg body weight slowly given intravenously immediately before the procedure for achieving sedation. Injection fentanyl 50 mcg intravenously given slowly just before introducing the ureteroscope into ureter for achieving intravenous analgesia. Patients were observed for few hours after completion of procedure and oral questions were asked as per proforma, which included tolerance, intensity of pain and percentage of pain experienced by the patients. Patients were discharged thereafter. Results: 87.10% of patients opined that the procedure was acceptable. Only 4.84% opined this procedure was painful. According to present pain intensity score (PPI) in this study 79.03 patients experienced only mild pain, 11.29% cases rated procedure as discomforting, 6.45 rated procedure as distressing and only 3.23% rated as horrible procedure. As per visual analogue scale for assessment of pain 80.65 of cases rated only 20% pain score (in a scale of 0–100). 9.68% cases rated 30% and 6.45% rated 50%. Only two patients in middle ureteric group rated 100% pain. Overall success rate in fragmenting stone was 91.94, where as for lower ureteric calculi it was 97.30%; for upper and, middle ureteric calculi it was 86.66% and 80%, respectively. Conclusion: Ureteroscopic lithotripsy can be performed on day care basis under sedoanalgesia which is fairly tolerated by the patients with unremarkable complications and difficulty.     

A new technique combining both polypropylene and vaginal wall sling procedures: can it minimize the risk of urethral and vaginal erosion occurring with synthetic materials?

We describe a new technique combining in situ vaginal wall and polypropylene mesh slings that may decrease potential erosive complications caused by synthetic materials. A folded mucosal patch harboring the polypropylene mesh was placed between mid-urethra and bladder neck. Using this technique, 12 consecutive women (age range 44–66 years) were operated. Preoperative evaluation included a detailed history, pelvic examination, stress test, cystourethroscopy, basic urodynamic evaluation (cystometry, Valsalva leak point pressure measurement), and urine culture. Based on these evaluations, three, seven, and two patients had type I, II, and III stress urinary incontinence, respectively. A paraurethral cyst excision was carried out in one patient and anterior colporrhaphy in four patients during the same operation. No ischemia or sloughing at the operation site occurred in any case. Pelvic examination was repeated in all patients after 3 and 6 months of follow-up and symptoms were determined after 12 months of follow-up in eight patients by telephone interview. Average follow-up was 10 months (range: 6–14 months). None of the patients were incontinent, or complained of sexual dysfunction or erosive complications after 1 year. Since there are two distinct barriers between the sling and both urethra and vagina, our technique covers all advantages of a sling procedure with synthetic materials and avoids the risk of urethral and vaginal erosion. The other advantage of this technique is the concomitant utilization of the vaginal wall as sling material.     

Spectacle-induced nasal dermochalasis—a new entity

The nasal skin is supported by a cartilaginous and bony framework. Due to the loose attachments between the skin and the underlying nasal bones, the radix skin is more mobile compared to the distal part of the nose. This, for example, affords simple primary closure of small skin defects, a process that is more demanding at the distal area overlying the cartilaginous framework. In this paper, we show that when continuous external load cycling force is applied over the radix skin, the combination of proximal skin mobility and distal anchoring may result in significant stretching of the radix skin. Three patients with excess radix skin due to prolonged external stretching by heavy spectacles are presented. We suggest calling this entity spectacle-induced nasal dermochalasis. To the best of our knowledge, although spectacles are the most prevalent medical aid used worldwide, this clinical entity has never been described before in the English literature.     

Preparation and physicochemical properties of scaffold materials of heterogeneous deproteinized bone

Objective:To prepare and observe the physicochemical properties of scaffold materials of heterogeneous deproteinized tissue-engineered bone. Methods: Deproteinized bone was made through a series of physicochemical treatments in pig ribs and analyzed with histological observation, scanning electron microscopy, infrared spectrum, X-ray diffraction and energy dispersive analysis, Kjeldahl determination and mechanics analysis. Results: Interstitial collagen fiber was positive and mucin was negative in deproteinized bone, but, both were positive in fresh bone. Deproteinized bone maintained natural pore network. Its pore size was 472.51μm±7.02μm and the porosity was 78.15%±6.45%. The results of infrared spectrum showed that collagen was present in deproteinized bone. Both fresh and deproteinized bone had curve of hydroxyapatite. The Ca/P ratios were 1.71±0. 95 and 1. 68±0. 76 ( P > 0. 05 ), and the protein contents were 26.6%±2.23% and 19.1%±2.14% (P < 0.05) in fresh and deproteinized bone, respectively. There was no significant difference of destruction load under compression and maximal destruction load between fresh and deproteinized bone (P > 0. 05). The elastic modulus was higher in deproteinized bone than that in fresh bone (P < 0.05). Conclusions:Physicochemical properties and mechanic strength of deproteinized tissue-engineered bone meet the demands of ideal scaffold materials. But, its immunogenicity should be observed through further experiments for its clinical applications.     

How are wear-related problems diagnosed and what forms of surveillance are necessary?

Prospective, randomized clinical wear studies have shown significant wear reduction when highly cross-linked, e-beamed, melted polyethylene was compared with conventional polyethylene sterilized by gamma irradiation in air. More complete assessment of wear-induced osteolysis in the general total hip arthroplasty patient population must rely on registries with follow-up of large populations of patients through radiographic evaluation of wear-related factors, such as suboptimal placement of the implant components, osteolytic defects, and aseptic loosening. Follow-up radiographs should be obtained in the early postoperative period and at 1, 5, and 10 years postoperatively, and then every 1 to 5 years, thereafter depending on radiographic findings of osteolysis and its progression. When pathologic findings are present, further examinations, such as oblique Judet views and magnetic resonance imaging (MRI) with artifact minimization should be considered to provide a better determination of the extent of the osteolysis. Because conventional radiographs underestimate the prevalence and extent of osteolysis in many instances, diagnosis and surveillance should be performed with radiographic edge detection, spiral computed tomography (CT), MRI, radiostereometric analysis, and quantitation of wear and osteolysis, including bone and soft-tissue lesions. Helical CT has demonstrated excellent specificity in identifying and quantifying the extent of osteolysis. MRI can more accurately localize both osseous and soft-tissue particulate disease, and detect granuloma and compression on adjacent nerves and vessels.     

Differences in erect sitting and natural sitting spinal alignment—insights into a new paradigm and implications in deformity correction

Background Context

Sitting spinal alignment is increasingly recognized as a factor influencing strategy for deformity correction. Considering that most individuals sit for longer hours in a “slumped” rather than in an erect posture, greater understanding of the natural sitting posture is warranted.