Tubular expression of angiotensin II receptors and their regulation in IgA nephropathy

Enhanced renal expression for the renin-angiotensin system (RAS) is detected in IgA nephropathy (IgAN). Previous data showed an altered glomerular expression of angiotensin II type 1 receptor (AT1R), suggesting a regulatory response to high intrarenal angiotensin II (Ang II) concentration in IgAN. In this study, the expression and regulation of Ang II receptors were examined in human proximal tubular epithelial cells (PTEC) in IgAN. Tubular expression of AT1R and Ang II type 2 receptor (AT2R) was increased in IgAN. In vitro culture experiment showed that the upregulation of Ang II receptors was not due to the direct effect of IgA but the indirect effect after IgA deposition on human mesangial cell. When PTEC were cultured with conditioned culture medium from human mesangial cells activated with IgA, Ang II production was upregulated, leading to inflammation and apoptosis via the AT1R and AT2R, respectively. Sequential expression of Ang II receptors determined the injury of PTEC induced by mediators in the conditioned medium. The initial interaction between Ang II and AT1R activated both protein kinase C and mitogen-activated protein kinase pathways, leading to inflammatory responses. This early AT1R-dependent event was followed by upregulation of AT2R expression and continued Ang II release. The interaction between Ang II and AT2R subsequently led to expression of cleaved poly[ADP-ribose] polymerase through downregulation of the mitogen-activated protein kinase pathway. The data suggest that appropriate control of Ang II receptor activities in PTEC may ameliorate tubulointerstitial injury in IgAN.     

Impact of the number of positive lymph nodes on disease-free survival in patients with pathological stage B1 nonseminomatous germ cell tumor

PURPOSE: The prognostic significance of the number of metastatic lymph nodes detected at surgery on survival is well documented for breast and colon cancer, and it has recently been reported in bladder cancer. We tested this hypothesis in patients with pathological stage B1 nonseminomatous germ cell tumor (NSGCT). MATERIAL AND METHODS: This series included 118 patients with pathological stage B1 NSGCT (5 or fewer positive lymph nodes) at primary retroperitoneal lymph node dissection who did not receive adjuvant chemotherapy at a followup of greater than 24 months. RESULTS: Five-year disease-free survival (DFS) was 68% at a median followup of 43 months. Median followup in patients without recurrence was 67.4 months and median time to recurrence was 5.0 months. The mean and median number of positive lymph nodes was 2.0. Five-year DFS for 1 or 2 and 3 to 5 positive lymph nodes was 72% and 59%, respectively (p = 0.0847). Five-year DFS for lymph node density less or greater than 0.05 was 75% and 66%, respectively (p = 0.261). Neither the number of positive lymph nodes (continuous and categorical p = 0.201 and 0.271) or the ratio of the number of positive lymph nodes to the total number resected (continuous and categorical p = 0.415 and 0.998, respectively) predicted recurrence. CONCLUSIONS: Primary retroperitoneal lymph node dissection is curative in patients with pathological stage B1 NSGCT and DFS does not seem to be influenced by the number or the ratio of positive lymph nodes resected. This information may be helpful in limiting adjuvant chemotherapy in patients otherwise cured by surgery.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.     

Magnetic resonance imaging as a diagnostic tool for breast cancer in premenopausal women

BACKGROUND: Screening mammography has led to earlier diagnosis of breast cancer; however, the increased tissue density of young women can complicate mammographic interpretation. We hypothesized that magnetic resonance imaging (MRI) has value in detection of mammographically occult breast cancers, particularly in premenopausal women for whom the sensitivity of mammography is compromised. METHODS: Data were available for 89 women with biopsy-proven breast cancer who had undergone both mammography and breast MRI. Variables evaluated included menopausal status and radiographic findings. Data were analyzed using Fisher's Exact test; P < .05 was considered significant. RESULTS: Of the 89 women in our study, 69 were perimenopausal or postmenopausal and 20 were premenopausal at the time of diagnosis. The malignant lesion was identified on mammography and MRI for a majority of patients. One third of premenopausal women had negative mammography but positive MRI findings. CONCLUSIONS: Our findings support a role for breast MRI in supplementing conventional mammography for early detection of breast cancer in premenopausal women.     

Long-term reendothelialization of excimer laser-assisted nonocclusive anastomoses compared with conventionally sutured anastomoses in pigs

OBJECT: In contrast to conventional anastomosis methods, the excimer laser-assisted nonocclusive anastomosis (ELANA) technique involves a platinum ring and intima-adventitia apposition with a rim of medial and adventitial layers exposed to the bloodstream. The authors assessed the reendothelialization of porcine carotid arteries through ELANA compared with conventional anastomosis by using scanning electron microscopy. METHODS: In 28 pigs a bypass with one ELANA and one conventional anastomosis was made on the left common carotid artery. All patent anastomoses were evaluated intraoperatively with the aid of an ultrasonographic flowmeter and postoperatively by using scanning electron microscopy at 2 weeks, 2 months, 3 months, and 6 months thereafter. Twenty-four of 28 bypasses (48 of 56 end-to-side anastomoses) were fully patent at the time of evaluation. On scanning electron microscopic evaluation of the bypasses, all 48 patent anastomoses showed complete reendothelialization, including all 24 ELANAs in which the endothelium covered the rim and the laser-ablated edge completely. No endothelial difference was observed between conventional anastomoses and ELANAs, aside from the obvious anatomical differences like the platinum ring, which had been completely covered with endothelium. At 6 months postsurgery, remodeling of the ELANA was observed, leaving the ring covered with a layer of endothelium as the most narrow part of the anastomosis. CONCLUSIONS: In long-term experiments, ELANA allows reendothelialization comparable to that achieved with conventional anastomosis. Considering its nonocclusive and high-flow characteristics, the ELANA technique is preferable in cerebral revascularization procedures.     

Topical vascular endothelial growth factor reverses delayed wound healing secondary to angiogenesis inhibitor administration

The prevention of new blood vessel growth is an increasingly attractive strategy to limit tumor growth. However, it remains unclear whether anti-angiogenesis approaches will impair wound healing, a process thought to be angiogenesis dependent. Results of previous studies differ as to whether angiogenesis inhibitors delay wound healing. We evaluated whether endostatin at tumor-inhibiting doses delayed excisional wound closure. C57/BL6J mice were treated with endostatin or phosphate-buffered solution 3 days prior to the creation of two full-thickness wounds on the dorsum. Endostatin was administered daily until wound closure was complete. A third group received endostatin, but also had daily topical vascular endothelial growth factor applied locally to the wound. Wound area was measured daily and the wounds were analyzed for granulation tissue formation, epithelial gap, and wound vascularity. Endostatin-treated mice showed a significant delay in wound healing. Granulation tissue formation and wound vascularity were significantly decreased, but reepithelialization was not effected. Topical vascular endothelial growth factor application to wounds in endostatin-treated mice resulted in increased granulation tissue formation, increased wound vascularity, and wound closure approaching that of control mice. This study shows that the angiogenesis inhibitor endostatin delays wound healing and that topical vascular endothelial growth factor is effective in counteracting this effect.     

Acute kidney injury, mortality, length of stay, and costs in hospitalized patients

The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.     

Simple Technique for Lip and Nasolabial Fold Anesthesia for Injectable Fillers

BACKGROUND: Minimally invasive cosmetic facial surgery procedures including injectable lip fillers are more popular than ever. Many of the newer fillers are more painful to inject than previous products and require a greater level of pain control. OBJECTIVE: The objective of this article is to describe a simple method of local anesthesia infiltration for pain control when injecting filler substances into the lips and perioral and nasolabial fold areas. MATERIALS AND METHODS: The preinjection topical anesthetic preparation, the actual infiltration techniques, and the author's experience are reviewed. RESULTS: These infiltration techniques are simple to perform and provide adequate anesthesia for the painless injection of filler substances in the lips and perioral, nasolabial regions. CONCLUSION: This simple intraoral infiltration technique is well tolerated and appreciated by patients and facilitates the experience of filler injection for both the patient and the doctor.     

The utility of capsule endoscopy and its role for diagnosing pathology in the gastrointestinal tract

BACKGROUND: Capsule endoscopy (CE) is a new device that enables visualization of areas of the small bowel that were previously inaccessible through other noninvasive procedures. The purpose of this study is to evaluate this new diagnostic tool and its efficacy in finding occult GI tract pathology. METHODS: A single-institution retrospective review was completed on patients undergoing CE from January 2002 to September 2004. Data evaluated included indications for CE, results of previous studies, CE findings, and complications of the CE study. RESULTS: A total of 702 CE studies in 652 patients were performed during the study period. Suspicious GI bleeding presenting as anemia, guaiac positive stools, or history of gross bleeding were the most common reasons to perform CE (75.8%). Other indications included abdominal pain (11.5%), diarrhea (3.1%), or others (9.5%). In studies performed for GI bleeding (N = 532), a source was found in 49.3% of CE studies. Arteriovenous malformation (AVM) was the most common reported finding (43.9%), followed by ulcer (24.1%), colon or gastric pathology (14.1%), mass/tumor (9.1%), and stricture (6.9%). Patients with abdominal pain (n = 81) had findings 46.9% of the time including edema/ulcer (47.4%), stricture (10.5%), mass/tumor (26.3%), gastric pathology (10.5%), AVM (2.6%), or sprue (2.6%). Patients with diarrhea (n = 22) had findings 45.5% of the time including edema/ulcer (75%), mass/tumor (12.5%), or sprue (12.5%). A total of 66 patients underwent operative exploration after a CE study at this institution either because of the observed findings or for other reasons. There were 12 (1.7%) CE studies in which the capsule was retained and required surgical removal. Pathology at the retention site included benign strictures or adhesions (n = 9, 75%), Crohn's stricture (n = 1, 8.3%) carcinoid tumor (n = 1, 8.3%), and villous adenoma (n = 1, 8.3%). CONCLUSIONS: CE is an accurate study to locate abnormalities in the GI tract that may have either been missed by previous diagnostic studies or cannot be observed through other non-invasive means. When used for diagnostic challenges such as GI bleeding with no apparent source, CE can be helpful in guiding surgical decisions in patients and thus should be integrated as part of the diagnostic workup.     

Clinical diagnosis of vertebrobasilar insufficiency: resident's case problem

STUDY DESIGN: Resident's case problem. BACKGROUND: Vertigo and visual disturbances are common symptoms associated with vertebrobasilar insufficiency (VBI), but the physical examination procedures to verify the existence of VBI have not been validated in the literature. The objective of this resident's case problem is to demonstrate how a patient's complaint of vertigo and visual disturbances, combined with positive clinical examination findings, can be a potential medical screening tool for VBI. DIAGNOSIS: The patient in this report was initially referred to physical therapy for neck pain. However, the patient's chief concerns identified during the history were (1) vertigo, (2) visual disturbances, (3) headache, and (4) right shoulder region pain. Clinical VBI tests were performed, whereby the patient's vertigo and visual disturbances were reproduced with cervical spine extension. The patient was sent back to the referring physician to be evaluated for possible VBI. Diagnostic imaging tests were ordered. Carotid ultrasound revealed 80% to 90% stenosis in the proximal left internal carotid artery, and magnetic resonance angiography of the extracerebral vessels showed greater than 90% stenosis of the left internal carotid artery. DISCUSSION: VBI may be present in patients with subjective reports of vertigo and visual disturbances that are reproduced with VBI physical examination procedures.