Barbu Gociman

Effects of Dietary Sodium and Genetic Background on Angiotensinogen and Renin in Mouse

Elements of a renin-angiotensin system expressed along the entire nephron, including angiotensinogen secreted by proximal tubule and renin expressed in connecting tubule, may participate in the regulation of sodium reabsorption at multiple sites of the nephron. The response of this tubular renin-angiotensin system to stepwise changes in dietary sodium was investigated in 2 mouse strains, the sodium-sensitive inbred C57BL/6 and the sodium-resistant CD1 outbred. Plasma angiotensinogen was not affected by sodium regimen, whereas plasma renin increased 2-fold under low sodium. In both strains, the variation in urinary parameters did not parallel the changes observed in plasma. Angiotensinogen and renin excretion were significantly higher under high sodium than under low sodium. Water deprivation, by contrast, induced significant activation in the tubular expression of angiotensinogen and renin. C57BL/6 exhibited significantly higher urinary excretion of angiotensinogen than did CD1 animals under both conditions of sodium intake. The extent to which these urinary parameters reflect systemic or tubular responses to challenges of sodium homeostasis may depend on the relative contribution of sodium restriction and volume depletion.

Overexpression of mouse angiotensinogen in renal proximal tubule causes salt-sensitive hypertension in mice.

BACKGROUND The role of proximal tubule (PT) angiotensinogen (AGT) in modulating blood pressure has previously been examined using mice expressing PT human AGT and human renin, or rat AGT. These animals are hypertensive; however, the question remains whether alterations in mouse PT AGT alone affects arterial pressure. METHODS Mouse AGT cDNA was knocked-in to the endogenous kidney androgen protein (KAP) gene using an internal ribosomal entry site (IRES)-based strategy. RESULTS The KAP-mAGT animals showed kidney-specific KAP-AGT mRNA expression; renal in situ hybridization detected KAP-AGT mRNA only in PT. Urinary AGT was markedly increased in KAP-mAGT mice. On a high Na diet, radiotelemetric arterial pressure showed a systolic pressure elevation; no significant difference in arterial pressure was observed on a normal diet. Plasma renin concentration (PRC) was reduced in KAP-mAGT animals given a high Na diet, but was not different between mouse lines during normal Na intake. Plasma AGT concentration was not altered by overexpression of PT mouse AGT. CONCLUSIONS In summary, PT overexpression of mouse AGT leads to salt-sensitive hypertension without recruitment of the systemic renin-angiotensin system.

Minimally invasive strip craniectomy for sagittal synostosis.

Abstract The most common approaches used today for the correction of sagittal synostosis involve large craniectomies and extensive cranial vault remodeling. Although these techniques ultimately yield very good cosmetic results, they have significant drawbacks. They are lengthy, expensive, associated with significant blood loss, universally require transfusions, and often result in prolonged hospitalization. We present here our 5-year experience with correction of sagittal synostosis using the recently described minimally invasive strip craniectomy followed by postoperative cranial vault helmet molding. During this period, we treated a total of 97 children with nonsyndromic single-suture synostosis. The first 46 of 67 children treated for sagittal synostosis had at least 1 year of postoperative follow-up and were included in the analysis. There were 33 boys and 13 girls. Patients’ mean age at surgery was 3.1 months, and the mean weight was 6.1 kg. The mean operative time was 75 minutes. The estimated blood loss during the procedure was 56 mL. Eight patients received blood transfusions during surgery (17.4%) and 3 patients received after surgery (6.5%). There were no significant postoperative complications. The mean hospitalization was 2.2 days. Excellent aesthetic outcomes were noted in all patients. The change in cranial index from a preoperative value of 0.7 to 0.8 postoperatively was virtually stabilized 3 months after the surgical intervention. Significantly better correction rates were observed in the youngest patients. Because of its excellent attributes, minimally invasive strip craniectomy followed by postoperative helmet molding is likely to become the preferred treatment modality for the correction of sagittal synostosis.

Endoscopic-assisted correction of metopic synostosis.

AbstractOur 6-year experience with correction of metopic synostosis using a minimally invasive endoscopic-assisted technique followed by postoperative cranial vault helmet molding is presented. In addition, a simple, objective method for quantification of the frontal vault contour is described.A total of 16 patients, 13 males and 3 females, with nonsyndromic, single-suture synostosis were included in the study. Patient age at operation averaged 2.9 months and the mean weight was 6 kg. The mean operative time was 79 minutes. The estimated blood loss during the procedure was 82.8 mL. Three patients required blood transfusions (18.7%). There were no significant postoperative complications. The mean hospitalization was 1.6 days. The average surgical cost, including the helmets, was

Surgical Excision of Non-Melanoma Skin Cancer in an Elderly Veteran's Affairs Population.

12,400, in contrast to

Response to genetic manipulations of liver angiotensinogen in the physiological range

33,000 charged for the equivalent open procedure.Very good esthetic results, judged by physical examination and photograph comparison, were obtained in all patients. No relapses were noted. Objectively, the outcome of the operative repair was evaluated using laser scanning. For quantification of the distortion and the postoperative level of correction, the metopic angle was defined and used. This angle changed from preoperative value of 104.9 degrees to 111.3 degrees at 3 months (P = 1.59E−06) and to 114.9 degrees at 1 year postoperatively (P = 2.51E−09).Due to its promising attributes, minimally invasive strip craniectomy emerges as an ideal modality for correction of metopic synostosis. Furthermore, the metopic angle should provide clinicians with an objective measure of the frontal cranial vault deformity and its correction.

Neonatal Ear Molding: Timing and Technique

Background: Non–melanoma skin cancer (NMSC) is the most common malignancy in the United States. Recommended treatment for NMSC remains surgical excision following a positive biopsy. Evidence of complete spontaneous regression of residual NMSC exists in the case of small lesions macroscopically removed by shave biopsy, but with a positive microscopic margin. The present study investigates the rate at which residual tumor is present at subsequent excisional biopsy, with the aim to assess if recommendation to forgo surgical excision can be made. Methods: A total of 233 shave biopsies of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) were performed during a 5-year period. All specimens included in the study were less than 2 cm in diameter, were macroscopically removed by shave biopsy, and had a positive initial microscopic margin. Results: On subsequent surgical excisional biopsy, 42% of BCC specimens were negative for residual tumor, 38% had residual tumor, but the tumor was completely contained in the excised specimen, and 20% of the specimens had positive margin residual tumor. For SCC specimens, 73% were negative for residual tumor, 21% had residual tumor, but the tumor was completely contained in the excised specimen, and 6% of the specimens had positive margin residual tumor. Conclusions: Although reduction of residual tumor at reexcision is noted with both BCC and even more so with SCC, the rate at which this occurs is not sufficient that a general recommendation to forgo surgical excision can be made.

The metopic angle: a novel assessment tool of the trigonocephalic frontal deformity and its correction.

AbstractGenetic variation in the human angiotensinogen gene (AGT) influences plasma AGT concentration and susceptibility to essential hypertension by a mechanism that remains to be clarified. When one or two additional copies of the gene were inserted by gene titration (by homologous recombination with gap-repair at the AGT locus), both plasma AGT and arterial pressure were elevated in the physiological range in the mouse. The causal dependency between plasma AGT and blood pressure and the relative contribution of the various tissues that express AGT to these two phenotypic parameters remained to be determined. To address these issues, we generated a transgenic mouse with overexpression of the mouse AGT gene restricted to the liver. The transgene was examined in two contrasted genetic backgrounds, the sodium-sensitive C57BL/6J and the sodium-resistant A/J. Transgenic and control male animals underwent continuous cardiovascular monitoring by telemetry for 14 days while under a standard sodium diet (0.2%). Moderate but significant increases in plasma AGT (40%, p = 0.01) and systolic blood pressure (4-6 mmHg, p ranging from 0.01 to <0.001) were observed in the sodium-sensitive background, but not in the sodium-resistant animals. Statistical analysis of a large number of consecutive, repeated measurements of blood pressure afforded power to detect small effects in the physiological range by use of advanced mixed models of analysis of variances and covariances. Although plasma renin activity was increased in the sodium-sensitive background, it did not reach statistical significance. These observations underline a potential contribution of systemic AGT to the mechanism of AGT-mediated hypertension, but the significance of sodium sensitivity in the genetic background suggests participation of the kidney in expression of the elevated blood pressure phenotype, a matter that will warrant further studies. They also highlight the challenge of identifying the contribution of individual genes in complex inheritance, as their effects are modulated by other genetic and environmental determinants.

Distraction Osteogenesis Technique for the Treatment of Nonsyndromic Sagittal Synostosis.

The incidence of auricular deformities is believed to be ∼11.5 per 10 000 births, excluding children with microtia. Although not life-threatening, auricular deformities can cause undue distress for patients and their families. Although surgical procedures have traditionally been used to reconstruct congenital auricular deformities, ear molding has been gaining acceptance as an efficacious, noninvasive alternative for the treatment of newborns with ear deformations. We present the successful correction of bilateral Stahl’s ear deformity in a newborn through a straightforward, nonsurgical method implemented on the first day of life. The aim of this report is to make pediatric practitioners aware of an effective and simple molding technique appropriate for correction of congenital auricular anomalies. In addition, it stresses the importance of very early initiation of ear cartilage molding for achieving the desired outcome.

Abstract: The Use of Bilateral Paraspinous Muscle Flaps and Bilateral Composite Latissimus Dorsi and Gluteus Maximus Flaps for Closure of Lumbosacral Myelomeningcele Defects in Infants

Abstract While metopic synostosis is typically a straightforward clinical diagnosis, there is no standard objective measurement that can be easily used in the preoperative evaluation and in the subsequent postoperative follow-up. Despite the fact that multiple methods have been previously described, they either lack well-defined landmark points, do not specifically address the frontal vault deformity, or are too cumbersome to be used routinely for clinical applications. We describe the metopic angle as an objective and dependable method for evaluation of the frontal vault contour. Using the STARscanner Laser Data Acquisition System, a portable, noninvasive diagnostic modality, the metopic angle was defined. This angle was used to track postoperative changes and was compared with preoperative values in patients who underwent minimally invasive strip craniectomy for metopic synostosis. To further ensure its validity, the angle was also measured in age-matched control subjects. The metopic angle changed from a preoperative value of 104.9 degrees to 111.3 degrees at 3 months (P = 1.59E−06) and to 114.9 at 1 year postoperatively (P = 2.51E−09) in patients who underwent endoscopic-assisted strip craniectomies for metopic synostosis. The resulting postoperative values were comparable to those obtained in age-matched control subjects with normal cranial vaults. The metopic angle measurement is a rapid, noninvasive, reproducible method for objective measurement of both preoperative deformity and postoperative correction of the frontal bone contour in metopic synostosis.