Combining lisinopril and l-arginine slows disease progression and reduces endothelin-1 in passive Heymann nephritis

BACKGROUND: Despite angiotensin-converting enzyme (ACE) inhibition is a very powerful therapy, it may not be uniformly renoprotective in patients with proteinuric nephropathies who might refer late in the course of the disease. In accelerated passive Heymann nephritis (PHN), a severe rat model of human membranous nephropathy, with proteinuria and increased urinary excretion of endothelin-1 (ET-1), early treatment with an ACE inhibition limited proteinuria as well as the exuberant formation of renal ET-1, while late treatment reduced urinary proteins not to a significant extent. Since biologic effects and production of ET-1 within the kidney are counteracted by nitric oxide, we studied the effect of combining lisinopril and l-arginine, the natural precursor of nitric oxide, starting late in the disease. METHODS: Uninephrectomized PHN rats were divided in four groups (N = 10) and daily given orally: vehicle; 1.25 g/L l-arginine; 40 mg/L lisinopril; and l-arginine + lisinopril. Treatments started at 2 months, when rats had massive proteinuria, until 9 months. Six normal rats served as control. RESULTS: Increase in systolic blood pressure was significantly limited by l-arginine. Lisinopril alone and the combination were more effective. Renal function impairment was not affected by l-arginine, partially ameliorated by ACE inhibitor and normalized by the combined therapy. In rats given l-arginine, proteinuria levels were similar to vehicle. ACE inhibitor kept proteinuria at values comparable to pretreatment and numerically lower than vehicle. Addition of l-arginine to lisinopril was more effective, with values significantly lower than vehicle. Glomerular and tubular changes were limited by the ACE inhibitor and further ameliorated by the combined therapy. Exaggerated urinary ET-1 of PHN was reduced by 23% and 40% after l-arginine and lisinopril, respectively, and by 62% with the combination. Defective urinary excretion of cyclic guanosine monophosphate (cGMP) was partially restored by lisinopril, while normalized by the combined therapy. CONCLUSION: Combining l-arginine with ACE inhibitors would represent a novel strategy for patients with severe nephropathy not completely responsive to ACE inhibition. Restoring the nitric oxide/ET-1 balance could be of benefit in halting renal disease progression.     

Cardiovascular Health among Black and White Breast Cancer Patients Initiating Aromatase Inhibitor Therapy

The purpose of this study was to compare the cardiovascular health of Black and White breast cancer patients undergoing adjuvant treatment. Baseline data from a cohort study of Black (n = 45) and White (n = 101) breast cancer patients initiating aromatase inhibitor treatment were analyzed. Participants had a cardiovascular health assessment, including carotid intimal medial thickness measurement, donated a blood sample, and completed a questionnaire. Atherosclerotic cardiovascular disease (ASCVD) event risk scores were calculated. Compared to their White counterparts, the Black patients had a significantly higher median ASCVD risk score (p = 0.009) and had a higher number of CVD risk factors (p < 0.05). Black patients were also more likely to have hypertension, diabetes, or to be obese than the White participants. The prevalence of cardiovascular disease and cardiovascular disease risk factors among Black and White breast cancer patients is high, and racial disparities exist which may have treatment implications.     

Responsiveness and minimum important change of the Oswestry Disability Index in Italian subjects with symptomatic lumbar spondylolisthesis

Background

This study aims to investigate the responsiveness and the minimum important change of the Italian version of the Oswestry Disability Index (ODI-I) in subjects with symptomatic specific low back pain associated with lumbar spondylolisthesis (SPL).

Materials and methods

One hundred and fifty-one patients with symptomatic SPL completed the ODI-I, a 0–100 numerical rating scale (NRS), and performed the prone and supine bridge tests. The global perception of effectiveness was measured with a 7-point Likert scale. Responsiveness was assessed by distribution methods (minimum detectable change [MDC], effect size [ES], standardized response mean [SRM]) and anchor-based methods (ROC curves).

Results

The MDC was 4.23, the ES was 0.95 and the SRM was 1.25. ROC analysis revealed an area under the curve of 0.76 indicating moderate discriminating capacity. The best cut-off point for the dichotomous outcome was 7.5 (sensitivity 90.3%, specificity 56.7%). .

Conclusions

The ODI-I proved to be responsive in detecting changes after conservative treatment in subjects with lumbar SPL.

Level of evidence

II.

     

Salivary Gland Tumor: A Review of 599 Cases in a Brazilian Population

Salivary gland tumors consist of a group of heterogeneous lesions with complex clinicopathological characteristics and distinct biological behaviors. Worldwide series show a contrast in the relative incidence of salivary gland tumors, with some discrepancies in clinicopathological data. The main aim of this study was to describe demographic characteristics of 599 cases in a population from Central Brazil over a 10-year period and compare these with other epidemiological studies. Benign tumors represented 78.3% of the cases. Women were the most affected (61%) and the male:female ratio was 1:1.6. Parotid gland tumors were the most frequent (68.5% of cases) and patient age ranged from 1 to 88 years-old (median of 45 years old). The most frequent tumors were pleomorphic adenomas (68.4%) and benign tumors were significantly more frequent in the parotid (75.9%), while malignant tumors were more frequent in the minor salivary glands (40%) (P < 0.05). In conclusion, women and the parotid gland were the most affected and pleomorphic adenoma was the most frequent lesion, followed by adenoid cystic carcinoma and Warthin’s tumor.     

Titanium wound chambers for wound healing research

Standardized and reproducible animal models are crucial in medical research. Rodents are commonly used in wound healing studies since, they are easily available, affordable and simple to handle and house. However, the most significant limitation of rodent models is that the wounds heal by contraction while in humans the primary mechanisms of healing are reepithelialization and granulation tissue formation. The robust contraction results in faster wound closure that complicates the reproducibility of rodent studies in clinical trials. We have developed a titanium wound chamber for rodent wound healing research. The chamber is engineered from two pieces of titanium and is placed transcutaneously on the dorsum of a rodent. The chamber inhibits wound contraction and provides a means for controlled monitoring and sampling of the wound environment in vivo with minimal foreign body reaction. This technical report introduces two modalities utilizing the titanium chambers in rats: (1) Wound in a skin island model and, (2) Wound without skin model. Here, we demonstrate in rats how the “wound in a skin island model” slows down wound contraction and how the “wound without skin” model completely prevents the closure. The titanium wound chamber provides a reproducible standardized models for wound healing research in rodents.     

The risk of child abuse in infants and toddlers with lower extremity injuries

Purpose

The aim of this study was to assess the risk of child abuse in children younger than 18 months admitted to a pediatric trauma service with lower extremity injuries.

Methods

An Institutional Review Board-approved retrospective case series of children admitted to a regional pediatric trauma center with lower extremity injuries from 1998 to 2002 (n = 5497) was performed. Factors analyzed included age, injuries, and injury mechanism.

Results

Among 5497 trauma patients, the incidence of abuse was 104 (2%) of 4942 children 18 months or older and 175(32%) of 555 children younger than 18 months (odds ratio [OR], 21.4 ± 2.9, P < .001). There were 1252 (23%) patients with lower extremity injuries in the entire sample, and 66 of these were younger than 18 months. In the extremity trauma group, for patients 18 months or older, 16 (1%) of 1186 were abused compared with 44 (67%) of 66 patients younger than 18 months (OR, 146 ± 53, P < .001). Among all trauma patients younger than 18 months, 41 of 55 lower extremity fractures were linked to abuse, whereas 134 of 500 other injuries were caused by abuse (OR, 8.0 ± 2.6, P < .001). Among the 41 abuse-related fractures, femur fracture was the most common (22), followed by tibia fracture (14).

Conclusions

Among children 18 months or older, abuse is an uncommon cause of lower extremity trauma. In children younger than 18 months, lower extremity injuries, particularly fractures, are highly associated with child abuse. Clinicians must thoroughly investigate lower extremity injuries in this age group.     

Ascending aortic aneurysm after pediatric heart transplantation: case report of an unusual complication.

A 28-month-old boy, weighing 11 kg, with severe dilated cardiomyopathy, was transplanted on December 1995. Hypertension and supraventricular tachycardia were detected in the immediate post-operative period, with favorable outcome. After 5 months of clinically asymptomatic follow-up, a dilation in the ascending aorta was observed on routine echocardiogram. Nuclear magnetic resonance imaging (NMRI) confirmed an ascending aortic aneurysm, with a diameter of 38 mm. An operation was performed, a bovine pericardium patch was sutured with reconstruction of the aortic wall, excluding the aneurysm. Good recovery was obtained and the child was discharged on Day 7 postoperatively. A post-operative echocardiogram showed absence of the aortic aneurysm and good surgical results. Another NMRI was done 5 months later, showing an intact ascending aorta. After 64 months, the patients clinical condition was confirmed as normal by echocardiogram. Surgical treatment was successful and the positive results have been maintained.     

Surgical removal of subfoveal choroidal neovascular membranes in high myopia

· Background: A study was carried out to elucidate the anatomical and functional outcome after surgical excision of subfoveal choroidal neovascular membranes in high myopia. · Methods: Sixty-five patients with high myopia (≥6 diopters), well-defined subfoveal neovascular membranes on fluorescein angiography and preoperative visual acuity ≤20/100 were selected for surgery. A standardized surgical technique was used in all cases, by a single surgeon. The main outcomes assessed were Snellen visual acuity, surgical retinal pigment epithelium defect and postoperative perfusion of the choriocapillaris. Multifactor analysis of variance and chi-square/Fisher’s exact test statistics were used to assess the association between patients’ pre- and postoperative characteristics and outcome measures. · Results: Follow-up ranged from 6 to 48 months (mean 16 months). Mean postoperative visual acuity (0.18) was significantly better than mean preoperative visual acuity (0.09). Visual acuity improved by at least two lines in 29 eyes (45%) and was unchanged in 24 (37%). Overall, 43 eyes (66%) had visual acuity of 20/200 or better and 15 (23%), 20/60 or better. Predictive factors with a significant effect on final visual acuity were mean visual acuity, preoperative status of retinal pigment epithelium and postoperative perfusion of the choriocapillaris. Postoperative perfusion was detected in 31 (48%) of the total 65 eyes and in 12 (67%) of the 18 eyes with normal retinal pigment epithelium at baseline. The mean postoperative retinal pigment epithelium defect was 4.6 times larger than the original neovascular membrane. In selected patients, SLO macular scotometry showed areas of retained retinal sensitivity within the atrophic scar. · Conclusion: The natural history of subfoveal neovascularization in high myopia is rarely visually restorative. By contrast, surgical excision of the membranes is feasible and may restore visual acuity in selected patients. This therapeutic approach merits a formal multicenter clinical trial. Received: 27 August 1998 Revised version received: 9 November 1998 Accepted: 10 November 1998