A Modular Antigen Presenting Peptide/Oligonucleotide Nanostructure Platform for Inducing Potent Immune Response.

The design and development of vaccines, which can induce cellular immunity, particularly CD8+ T cells hold great importance since these cells play crucial roles against cancers and viral infections. Covalent conjugation of antigen and adjuvant molecules has been used for successful promotion of immunogenicity in subunit vaccines; however, the stimulation of the CD8+ T-cell responses by this approach has so far been limited. This study demonstrates a modular system based on noncovalent attachment of biotinylated antigen to a hybrid nanofiber system consisting of biotinylated self-assembling peptide and CpG oligodeoxynucleotides (ODN) molecules, via biotin-streptavidin interaction. These peptide/oligonucleotide hybrid nanosystems are capable of bypassing prior limitations related with inactivated or live-attenuated virus vaccines and achieve exceptionally high CD8+ T-cell responses. The nanostructures are found to trigger strong IgG response and effectively modulate cross-presentation of their antigen "cargo" through close proximity between the antigen and peptide/ODN adjuvant system. In addition, the biotinylated peptide nanofiber system is able to enhance antigen uptake and induce the maturation of antigen-presenting cells. Due to its versatility, biocompatibility, and biodegradability with a broad variety of streptavidin-linked antigens, the nanosystem shown here can be utilized as an efficient strategy for new vaccine development.

Antibiotic and hyperbaric oxygen therapy in the management of post-operative discitis.

OBJECTIVE: Despite the use of antibiotics, the management of postoperative discitis (POD) still presents a challenge. This study was designed to evaluate the effect of adjuvant hyperbaric oxygen (HBO2) therapy on the duration of antibiotic treatment. METHODS: Between 1999 and 2004, 22 patients diagnosed with POD were treated with antibiotic and HBO2 therapy. There were 14 male (63.6%) and 8 female (36.3%) patients, and their mean age at the time of surgery was 45.4 years (range, 20-59 years). Diagnosis of a POD was established on the basis of clinical, laboratory, and radiographic findings. All patients were given a 4-week course of vancomycin (1g i.v. every 12 h). Additionally, patients received HBO2 (100% O2 at 2.4 ATA for 90 min) twice daily for the initial five consecutive days, and an additional treatment (100% O2 at 2.4 ATA for 90 min daily) was given for 25 days. The duration of follow-up was 24 months. RESULTS: This treatment modality allowed infection control and healing for all 22 patients with 0% recurrence rate. HBO2 treatment was tolerated well. CONCLUSION: This series represents the first reported group of POD patients treated with antibiotic and HBO2 therapy. Our preliminary results indicate that the length of time on antibiotic therapy can be shortened with the use of HBO2 as an adjunctive treatment. Erythrocyte sedimentation rates and serum C-reactive protein levels returned to the preoperative levels earlier (within 8-30 days after the initiation of treatment) and a reasonable length of immobility was obtained (mean 12.2 days). After completion of the one-month period of antibiotic and HBO2 therapy, patients were accepted disease-free regarding pain and mobility.

Two-staged operation on C2 neoplastic lesions: anterior excision and posterior stabilization.

This retrospective study included eight consecutive cases with C2 vertebral body neoplastic lesions. The anterior retropharyngeal approach was used to remove the lesions and decompress the spinal cord. Spinal stabilization with occipitocervical plating in a second-stage operation makes the treatment more tolerable for patients. The object of this study was to determine the effectiveness of a two-stage operation strategy for these lesions. Eight patients were operated on via anterior retropharyngeal approach and then stabilized with occipitocervical plates posteriorly in a second sitting. All neck pain and all dysphagia problems resolved. Partial neurologic improvement was achieved in three out of four patients. No postoperative infection was seen. The retropharyngeal approach to the upper cervical spine and anterior foramen magnum lesions is an effective alternative to transoral surgery because of low complication rates. Neoplastic lesions in the upper cervical spine can safely and effectively be operated with this technique. The general medical status of patients with malignancies does not permit too long, time-consuming operations. Stabilization of the spine in a separate operation increases patient tolerability without any morbidity.

Multiple coronary artery aneurysms combined with abdominal aortic aneurysm.

Coronary artery aneurysm (CAA) is defined as coronary dilatation which exceeds the diameter of a normal adjacent segment or the diameter of the patients's largest coronary vessel by as much as 1.5 times. It is an uncommon pathology with a frequency of 1-4% in routine autopsies or coronary angiographies. Atherosclerosis plays an important role in the development of CAA, and it may be a predominant cause in the majority of patients. However, the timing of surgical intervention and the treatment options for CAA are still controversial. In this report, we present a patient who had multiple CAAs of all main coronary arteries and abdominal aortic aneurysm. Different treatment modalities and indications are also discussed.

Renal vascular changes in renal disease independent of hypertension.

INTRODUCTION: Cardiovascular disease is common in patients with renal disease, but little is known about the effect of renal disease and loss of renal function on vascular morphology. Intima proliferation of small renal arteries, which correlates with atherosclerosis in the aorta, is sometimes present in renal disease and has been shown to increase with age and hypertension. We studied the effect of chronic renal disease and renal function, independent of hypertension, on intima proliferation. METHODS: We retrospectively selected renal biopsies of subjects in whom a glomerular filtration rate (GFR) measurement with [(125)I] iothalamate had been performed. To separate the effects of renal disease and renal function, we selected biopsies from (A) normotensive controls undergoing nephrectomy because of renal carcinomas; (B) normotensive patients with renal disease and GFR > 90 ml/min; (C) normotensive patients with GFR 30-90 ml/min, and (D) hypertensive patients with a GFR < 90 ml/min. The area of the arteriolar lumen, intima, and media were measured. RESULTS: No significant changes from control subjects were observed in group B. Intima proliferation was observed when renal function declined (intima/total vessel surface ratio was 0.262 +/- 0.071 in group C, 0.192 +/- 0.032 in group A, and 0.205 +/- 0.035 in group B, P < 0.05). The intima proliferation was aggravated in patients with renal insufficiency and hypertension (0.333 +/- 0.121, P < 0.05). Media surface area was not different between groups. CONCLUSION: Renal disease with preserved GFR does not cause significant intima proliferation of small renal arteries. Loss of renal function is accompanied by intima proliferation, even in the absence of systemic hypertension.

Determination of serum bile acids routinely may prevent delay in diagnosis of total parenteral nutrition-induced cholestasis.

BACKGROUND/PURPOSE: Early diagnosis of development of cholestasis is a current major problem for patients receiving total parenteral nutrition (TPN). Conventional tests for hepatic function such as serum transaminases and alkaline phosphatase do not often reflect simultaneously histopathologic changes of the liver. The aim of this study is to find out the relationships between conventional hepatic function tests, total serum bile acid concentrations (TSBA), and the histopathologic changes in the liver during TPN administration in rats. METHODS: Forty Albino rats were divided into four experimental groups, each consisting of 10 rats, as follows: control group (C), 0.9% saline for 14 days; T7 group, TPN for 7 days; T14 group, TPN for 14 days; T7O7 group, TPN for 7 days and then 0.9% saline for the next 7 days. All solutions were administered by infusion through intraperitoneal catheter in two equal doses. During the experiment, rats also maintained on rat chow and water ad libitum. Levels of serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, and TSBA were measured. Liver was evaluated histopathologically by light microscope and then Morphological Cholestasis Index (MCI) was calculated. RESULTS: Cholestasis was present in all experimental groups except control. Levels of transaminases and alkaline phosphatase were not correlated with the histopathologic changes (P > .05), but TSBA concentrations were correlated with MCI in all groups (P< .01). TSBA concentrations and MCI in all groups also were correlated with the duration of exposure with TPN (P< .01). CONCLUSIONS: Measurement of TSBA seems to be more sensitive in early diagnosis of TPN-induced cholestasis. Therefore, periodical determination of TSBA during TPN administration can be done routinely.

The effects of acetylsalicylic acid, interferon-alpha, and vitamin E on prevention of parenteral nutrition-associated cholestasis: an experimental study.

BACKGROUND: Cholestasis is one of the major complications of parenteral nutrition. The purpose of this experimental study was to detect the effects of acetylsalicylic acid (ASA), vitamin E (Vit E), and interferon-alpha (IFN-alpha) on prevention of parenteral nutrition-associated cholestasis. METHODS: Ten experimental groups, each consisting of 10 4-week-old Wistar albino rats, were formed: control 10- and 20-day groups (C10 and C20), parenteral nutrition-only 10- and 20-day groups (T10 and T20), ASA-supplemented parenteral nutrition 10- and 20-day groups (TA10 and TA20), Vit E-supplemented parenteral nutrition 10- and 20-day groups (TE10 and TE20), and IFN-alpha-supplemented 10- and 20-day groups (TF10 and TF20). Acetylsalicylic acid, Vit E, and IFN-alpha were administered in the parenteral nutrition solution through an intraperitoneal route. At the end of the study, serum total bile acids, serum aspartate and alanine aminotransferases, and alkaline phosphatase were measured biochemically. In addition, the histopathologic findings of cholestasis were evaluated by using a morphologic portal inflammation index. RESULTS: Although the difference in the serum levels of transferases and alkaline phosphatase was not significant among all groups (p > 0.05), it was significant in total bile acid levels (p < 0.05). There was also a significant correlation between the histopathologic changes of the liver and serum total bile acid concentrations (p < 0.05). Portal inflammation in varying degrees was seen in all experimental groups, but not in the control groups. Serum total bile acid concentrations in parenteral nutrition groups receiving ASA were significantly lower than those in the parenteral nutrition-only group (p < 0.01). Although Vit E-supplemented parenteral nutrition was effective in preventing the development of cholestasis in the 10-day group (p < 0.05), it was not effective in the 20-day group when compared with incidence of cholestasis in the parenteral nutrition-only group (p > 0.05). Conversely, IFN-alpha-supplemented parenteral nutrition had no effect on cholestasis in the 10-day group (p > 0.05) but lowered cholestasis in the 20-day group when compared with incidence the parenteral nutrition-only group (p < 0.05). CONCLUSION: Our results indicate that acetylsalicylic acid may be beneficial in preventing, and (alpha-interferon in treating, parenteral nutrition-associated cholestasis.

Aluminum in total parenteral nutrition solutions produces portal inflammation in rats.

BACKGROUND: Aluminum contaminates parenteral nutrition solutions and accumulates in bone and liver of patients receiving total parenteral nutrition therapy. Although previous reports have shown that parenteral administration of aluminum in pharmacologic doses to rats results in the production of elevated total serum bile acid concentrations alone or in combination with decreased bile flow, they have failed to demonstrate any abnormalities in the histologic appearance of liver tissue. The effects of aluminum in total parenteral nutrition and of aluminum chloride on total serum bile acid concentrations, aluminum contents of the liver, and histopathologic changes in the liver were studied in rats. METHODS: The aluminum concentrations in the aluminum chloride solution and total parenteral nutrition formula were equal (300 microg/l). They were given intraperitoneally as follows: control group, 0.9% saline for 14 days; T7 group, total parenteral nutrition for 7 days; A7 group, aluminum chloride for 7 days; A14 group, aluminum chloride for 14 days; T7A7 group, total parenteral nutrition for 7 days and aluminum chloride for the next 7 days; and T7O7 group, total parenteral nutrition for 7 days and 0.9% saline for the next 7 days. Volumes of 0.9% saline, aluminum chloride, and total parenteral nutrition given to rats were equal. During the experiment, rats were maintained on rat chow and water ad libitum. Serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and bile acid concentrations and aluminum content of the liver were measured. The liver was evaluated histopathologically by light microscope, and a morphologic portal inflammation index was calculated. RESULTS: Portal inflammation was present in all groups except the control group. The morphologic portal inflammation correlated with hepatic aluminum accumulation in all groups and was the highest in the T7A7 group. Levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase did not correlate with the histopathologic findings, but serum bile acid concentrations correlated with morphologic portal inflammation and hepatic aluminum accumulation in all groups. Hepatic aluminum accumulation also correlated with the duration of exposure to total parenteral nutrition and aluminum chloride concentration. CONCLUSION: Aluminum in contaminating doses, not in pharmacologic doses, accumulates in the liver and can produce hepatobiliary dysfunction characterized by portal inflammation detectable in histologic examination of liver tissue.

Blood transfusion requirements in children with blunt spleen and liver injuries.

The records of 174 children sustaining blunt spleen and liver injuries in a 16-year period were analyzed retrospectively to determine blood transfusion requirements in surgically versus conservatively managed patients. The whole study group consisted of 97 spleen, 70 liver, and 7 combined spleen and liver injuries respectively. Seventy-eight patients were managed conservatively while 96 children had undergone various operative procedures. The hematocrit (Hct) values, transfused blood volumes (ml/kg), and length of hospital stay were compared between the non-operative and operative treatment groups. Although the initial Hct values were found to be similar in non-operative versus operative groups (26.7% +/- 2.7% vs. 24.8% +/- 3.5%), transfused blood volumes were significantly higher in the surgically treated group respectively (20.9 ml/kg vs. 39.5 ml/kg) (p < 0.05). Similarly, mean length of hospital stay was longer in the surgical groups. Associated injuries were seen in 105 (60.3%) patients distributed randomly among two study groups. Twelve patients in the series died of other system/organ involvement. There were no deaths in isolated spleen and/or liver injuries. Increased blood transfusion requirement in surgical groups may be due to excessive bleeding prior to the operation which virtually provides the indication for laparotomy. Manipulation and suturing enhances additional bleeding to elevate the total volume to be delivered. Operative choice should be spared for very selected cases, and conservative management is safe; procedures such as splenorrhaphy are not superior to observation therapy as a means of controlling intraabdominal bleeding.

Pilomatricoma in children: a prospective study.

Pilomatricoma is a skin appendage tumor that frequently involves the skin of the head, neck, and upper extremities in young children. In this prospective study, we present and discuss the characteristics of our patients with pilomatricoma. During the years 1984 to 1994, 15 children (9 girls and 6 boys) with pilomatricoma were admitted to our service. Their ages ranged from 3 to 13 years (mean age 9 years). All of the lesions of these patients were excised totally. On histopathologic examination, calcification was found in all of the specimens. No invasion or malignancy was observed by light microscopy. All patients have been followed up periodically by the same surgeons. Interestingly, we found two familial occurrences and four multiple occurrences. Although our series was too small for accurate statistical evaluation, multiple and familial occurrences of pilomatricoma (26.7% and 13.3%, respectively) were higher than in previously reported series.

Neonatal bladder rupture: an unusual complication of umbilical catheterization.

Bladder injury in the neonatal period is an exceedingly rare phenomenon that is usually iatrogenic. Bladder rupture as a complication of umbilical catheterization in a newborn with urinary ascites, respiratory distress and hematuria is presented and discussed.

Gastroesophageal reflux: a determinant in the outcome of caustic esophageal burns.

Deep circumferencial burns of the esophagus always result in stricture formation and obstruction of the lumen. The usual treatment of caustic esophageal strictures is long-term esophageal dilatations. A new method of treatment, long-term stenting of the strictured esophagus gave superior results when compared with the classic dilatation therapy (healing rates, 68% v 33%; P < .01). Although success in the stent group was very satisfactory, the 32% failure rate requires explanation. In the years between 1991 and 1993, 53 stent-treated patients were screened for gastroesophageal reflux (GER). All patients were investigated with 24-hour ambulatory distal esophageal pHmetry. In 18 patients reflux index (RI) was found to be below 4. In 14 patients RI was between 4.1 and 19. In the final group of 21 patients RI was over 20 (minimum, 21.8; maximum, 72.8). When these data were compared with the healing rates of the patients, it was found that none of the 21 patients with RI over 20 responded to the described therapy. We conclude that the esophagus, after a serious caustic insult, not only narrows but also shortens thus altering the lower esophageal sphincter function leading to serious GER. Therefore all caustic esophageal burn patients should be screened for GER periodically during the dilatation or stent therapy programs, and GER should be controlled before RI approaches 20.

Gastrointestinal perforations in children: a continuing challenge to nonoperative treatment of blunt abdominal trauma.

The present trend towards conservative management of hemodynamically stable pediatric trauma patients may be increasing the risk of delay in the diagnosis of traumatic hollow viscus perforations (HVP). The purpose of this study is to determine whether there is a delay in the diagnosis of HVP because of expectant management. A survey of factors leading to diagnostic delay was also made and the value of current diagnostic tools were reevaluated. In 1,283 trauma admissions between 1980-1994, 34 patients were operated for HVP caused by blunt abdominal trauma. Sites of perforation were; stomach (four), duodenum (five), jejunum (12), ileum (nine), and jejunum/ileum (four). Signs of peritoneal irritation were positive in 32 of 34 patients. There was free air in only six of 24 abdominal roentgenograms. Free peritoneal fluid without solid organ injury was detected in only four out of 13 patients with ultrasound. Peritoneal lavage was diagnostic in eight of nine patients. Time from admission to operating room averaged 24 +/- 4.1 (mean +/- standard deviation) hours. Eleven patients died after the operation mostly because of accompanying head injury. Only two of the deaths were the result of sepsis originating from the perforated bowel. There is an apparent delay in the diagnosis of traumatic HVP in this series. Signs of peritoneal irritation are the most consistent findings of HVP after blunt abdominal trauma in children. Persistence of abdominal signs indicates peritoneal lavage, which has a high diagnostic sensitivity for HVP compared to other diagnostic modalities.

Complete duplication of the hindgut, penis, and lower urinary tract.

A 1-day-old male with complete duplication of the caudal gut from the terminal ileum to the anus with a normal, midline-localized anus and an imperforate right-sided anus with a rectourethral fistula and a skin dimple is presented. He also had complete duplication of the bladder urethra, and penis (true diphallus), an umbilical hernia, spina bifida occulta covered by skin containing a capillary hemangioma, and separation of the symphysis pubis. This case represents caudal twinning with duplication of the hindgut, genitalia, and lower urinary tract.

Unilateral inguinal hernia in girls: is routine contralateral exploration justified?

To determine the incidence of contralateral hernia development after unilateral inguinal hernia repair in girls, collected case series from two large hospitals were analyzed retrospectively. Among the 294 girls who had analyzed repair of a unilateral inguinal hernia (during a 15-year period), 245 could be traced; the mean follow-up period was 8.4 years. In 25 (10.2%) of the patients, contralateral hernia developed, mostly within one year (4 months to 6.5 years). The incidence of contralateral hernia development with respect to the original side of the inguinal hernia was significantly higher (19%) for the originally left-sided hernias than for the right-sided ones (6%) (P < .01). Although the incidence of contralateral hernia development for girls with a left inguinal hernia decreased as age increased, it was still 14.9% for the girls age 3 and up. Contralateral exploration should not be routine for girls who have a right-sided hernia, at any age. For left-sided hernias, it may be performed routinely for girls up to 2 years of age, and selectively for older patients.

The Rapunzel syndrome: a case report and review of the literature.

The Rapunzel syndrome, found characteristically in girls with varying gastrointestinal symptoms, is a rare form of gastric trichobezoar extending throughout the bowel. The previously reported cases have different clinical and pathological features affecting the mortality. We describe a new case preoperatively diagnosed with none of the complications previously reported.

Segmental dilatation of intestine: a case report and review of the literature.

Segmental dilatation of intestine (SDI) is a rare disorder that leads to functional obstruction without stenosis and normally functioning ganglion cells. The etiology of the disease is unknown. Definitive treatment consists of segmental resection of the dilated segment with end-to-end anastomosis.