Controlled temperature-mediated curcumin release from magneto-thermal nanocarriers to kill bone tumors.

Systemic chemotherapy has lost its position to treat cancer over the past years mainly due to drug resistance, side effects, and limited survival ratio. Among a plethora of local drug delivery systems to solve this issue, the combinatorial strategy of chemo-hyperthermia has recently received attention. Herein we developed a magneto-thermal nanocarrier consisted of superparamagnetic iron oxide nanoparticles (SPIONs) coated by a blend formulation of a three-block copolymer Pluronic F127 and F68 on the oleic acid (OA) in which Curcumin as a natural and chemical anti-cancer agent was loaded. The subsequent nanocarrier SPION@OA-F127/F68-Cur was designed with a controlled gelation temperature of the shell, which could consequently control the release of curcumin. The release was systematically studied as a function of temperature and pH, via response surface methodology (RSM). The bone tumor killing efficacy of the released curcumin from the carrier in combination with the hyperthermia was studied on MG-63 osteosarcoma cells through Alamar blue assay, live-dead staining and apoptosis caspase 3/7 activation kit. It was found that the shrinkage of the F127/F68 layer stimulated by elevated temperature in an alternative magnetic field caused the curcumin release. Although the maximum release concentration and cell death took place at 45 °C, treatment at 41 °C was chosen as the optimum condition due to considerable cell apoptosis and lower side effects of mild hyperthermia. The cell metabolic activity results confirmed the synergistic effects of curcumin and hyperthermia in killing MG-63 osteosarcoma cells.

Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child.

PURPOSE: To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165. METHODS: A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre- and post-immunodepletion to remove complexed VEGF. RESULTS: Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection. CONCLUSIONS: These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults.

Intravenous magnesium sulfate for post-operative pain in patients undergoing lower limb orthopedic surgery.

INTRODUCTION: This study looks at the effect of supplementary intravenous magnesium sulfate on acute pain when administered in patients undergoing lower limb orthopedic surgery using spinal anesthesia with bupivacaine. METHOD AND MATERIALS: In this double-blind, randomized, placebo-controlled clinical trial, 60 patients were selected and randomly divided into two groups. Efforts were made to place both groups under the same method of anesthesia. One group received 8 mg/kg intravenous magnesium sulfate, started before the incision and continued up to the end of the surgical procedure, using a 50 ml syringe, via a peripheral large bore catheter; the second group received the same volume of placebos using the same method. To present the results, mean (+/- SD) was used; a P value of <0.05 was considered significant. RESULTS: There was no difference between the two groups in terms of the basic variables. Pain reported by the first group that received magnesium sulfate was significantly less at the first, third, sixth and 12th hours after the operation in comparison with the group that received placebo. Also, the intravenous morphine requirements in the first 24 h after the surgery were less in the magnesium group (4.2 +/- 1.6 mg) than in the control group (9.8 +/- 2.1 mg). CONCLUSION: Intravenous magnesium sulfate can serve as a supplementary analgesic therapy to suppress the acute post-operative pain, leading to less morphine requirements in the first 24 h.

Stump appendicitis. A diagnostic dilemma.

A case of stump appendicitis in a 41-year-old man is presented. Initial appendicectomy for suppurative appendicitis had been performed 14 months earlier. An ultrasound scan suggested the diagnosis of stump appendicitis despite the hindsight of previous appendicectomy. A literature review on the subject is provided. Stump appendicitis should be considered in the differential diagnosis of recurrent lower abdominal symptoms any time following initial appendicectomy. Knowledge of a difficult approach at initial surgery may raise the level of suspicion.

Effect of magnesium sulfate on extubation time and acute pain in coronary artery bypass surgery.

BACKGROUND: Post-operative pain control is one of the greatest concerns for both physicians and patients. In this study, the effect of magnesium sulfate (MgSO(4)) solution infusion on post-operative pain scores and extubation time in patients undergoing elective coronary artery bypass graft (CABG) surgeries was assessed. METHODS: In a double-blind, randomized, placebo-controlled clinical trial, 218 patients scheduled for elective CABG were selected and randomly assigned to two groups. After matching inclusion and exclusion criteria for the patients, intravenous MgSO(4) was administered intraoperatively for one group and placebo to the second group. Except for this, all the cases were similar regarding anesthesia and surgery. RESULTS: The MgSO(4) patients were extubated sooner compared with the placebo group. Pain scores reported by the group who received MgSO(4) were less at the 6th, 12th, 18th and 24th hours after the operation; also, they needed less morphine sulfate during this period. CONCLUSION: The results demonstrated a significantly shortened post-operative time for extubation and reduced acute post-operative pain scores by intravenous MgSO(4) infusion during elective CABG surgery.

Snaring of submucosal tumors of gastric fundus.

Submucosal tumors of the stomach are not uncommon. We present two cases of iatrogenic perforation after snaring large polyps in the gastric fundus. We discuss the probable etiology and review the literature regarding iatrogenic perforation in this location. Submucosal polyps situated in the fundus may produce pseudopedicle. Therefore, we recommend these be treated with caution, and a combined endoscopic and laparoscopic approach is suggested.

Surgical interventions at field hospitals during the Iran and Iraq War (1980-1987).

Surgical treatment of wounded soldiers in the field began in World War II, and the care of the wounded was aided by air, ground, and marine transportation. Even with highly developed facilities, medical care should be started as soon as possible. The Islamic Republic of Iran was under an economic blockade during its war with Iraq. Field hospitals were considered a solution to the problem of transportation shortages. The aim of this study was to assess the surgical interventions of these hospitals. In a descriptive cross-sectional study, data for 7,718 patients admitted to field hospitals (among a total of 173,823 casualties) were analyzed. A checklist was used as the data-collection tool. The data were entered and analyzed by the Statistical Program for the Social Sciences. The type of surgical intervention, duration of the surgery, and frequency of the interventions in each hospital were examined. Laparotomy was the most common and tracheostomy the least common intervention. Shahid Baghaei Field Hospital had the greatest number of admissions. Of all the patients in the Southern Command District who underwent any kind of surgery, 21.53% were operated on in the complex of field hospitals. The surgery time in these hospitals was 156 +/- 69 minutes (mean +/- SD). A great number of the procedures were lifesaving (including laparotomy and chest tube insertion). It seems that these hospitals played a key role in reducing mortality and morbidity during the war.

Therapeutic urogenital modalities during the last three years of the Iran and Iraq War (1985-1987).

OBJECTIVE: Research projects in the field of military medicine have a central role in medical logistical planning. Treatment of traumatic lesions (including urogenital system injuries) is an important aspect of military medicine. Triage for urogenital injuries has specific problems and points of concern. The purpose of this study was to evaluate the role and different types of therapeutic modalities in the treatment of urogenital injuries during the final 3 years of the Iran and Iraq War (1985-1987). METHODS: In a descriptive-analytical study, records of 1,094 patients with urogenital injuries hospitalized from 1985 to 1987 were studied. A checklist and the Statistical Program for the Social Sciences (version 6) were used for data collection and analysis, respectively. A chi 2 test interpreted part of the data. RESULTS: The highest incidence of urogenital injuries and the highest rate of surgical interventions for urogenital injuries were in 1986 and 1987, respectively. The total incidence of urogenital injuries was 0.51%. Among all surgical interventions, bladder repair was most frequent and ureteral repair was least frequent. Partial nephrectomy was the second most frequent surgical intervention and was performed more often than total nephrectomy. There was a significant difference between the urogenital surgery rate and the total surgery rate (chi 2 = 148, p = 0.000). CONCLUSION: The results suggest progress in the triage of patients with urogenital injuries. The lower incidence of urogenital injuries, however, should be interpreted cautiously because it may be attributable to different combat field conditions. Follow-up studies in this group of patients are necessary.

Effect of iron overload and iron deficiency on atherosclerosis in the hypercholesterolemic rabbit.

It has been suggested that iron plays an important role in the pathogenesis of atherosclerosis, primarily by acting as a catalyst for the atherogenic modification of LDL. Although some epidemiological data suggest that high stored iron levels are an independent risk factor for coronary artery disease and that iron has been detected in both early and advanced atherosclerotic lesions, the evidence is often contradictory and inconclusive. We used the New Zealand White rabbit to investigate the effects of iron overload (FeO) and iron deficiency (FeD) on atherosclerosis. Groups of 7 rabbits were either iron loaded by injections of iron dextran (FeO group), iron depleted by phlebotomy (FeD group), or given injections of saline (control group) for a total of 9 weeks. All rabbits were fed a chow diet containing 1% (wt/wt) cholesterol for the last 6 weeks of the study. Iron and antioxidant status and cholesterol levels were assayed in plasma before cholesterol feeding (week 3) and at the time that the rabbits were killed (week 9). In addition, the susceptibility of LDL to oxidation was measured and pathological examination of the aortic arch and thoracic aorta performed at the end of the study. FeD significantly decreased the levels of blood hemoglobin, serum iron, and transferrin saturation compared with controls. Conversely, FeO significantly increased transferrin Fe saturation. FeO but not FeD decreased plasma cholesterol levels compared with control animals both before (P < .05) and after (P = .055) cholesterol feeding. Neither FeO nor FeD had a significant effect on the levels of antioxidants and lipid peroxidation products in plasma and aortic tissue or on the susceptibility of LDL to ex-vivo oxidation. FeO significantly decreased aortic arch lesion formation by 56% compared with controls (P < .05), whereas FeD had no significant effect. These results indicate that in this animal model, FeO decreases rather than increases atherosclerosis, likely because iron dextran exerts a hypocholesterolemic effect. Our data do not support the hypotheses that elevation of Fe stores increases or that a reduction of Fe stores by phlebotomy decreases the risk of coronary artery disease.

Antioxidant activity of vitamin C in iron-overloaded human plasma.

Vitamin C (ascorbic acid, AA) can act as an antioxidant or a pro-oxidant in vitro, depending on the absence or the presence, respectively, of redox-active metal ions. Some adults with iron-overload and some premature infants have potentially redox-active, bleomycin-detectable iron (BDI) in their plasma. Thus, it has been hypothesized that the combination of AA and BDI causes oxidative damage in vivo. We found that plasma of preterm infants contains high levels of AA and F2-isoprostanes, stable lipid peroxidation end products. However, F2-isoprostane levels were not different between those infants with BDI (138 +/- 51 pg/ml, n = 19) and those without (126 +/- 41 pg/ml, n = 10), and the same was true for protein carbonyls, a marker of protein oxidation (0.77 +/- 0.31 and 0.68 +/- 0.13 nmol/mg protein, respectively). Incubation of BDI-containing plasma from preterm infants did not result in detectable lipid hydroperoxide formation (10% of its initial concentration. Finally, when iron was added to plasma devoid of AA, lipid hydroperoxides were formed immediately, whereas endogenous and exogenous AA delayed the onset of iron-induced lipid peroxidation in a dose-dependent manner. These findings demonstrate that in iron-overloaded plasma, AA acts an antioxidant toward lipids. Furthermore, our data do not support the hypothesis that the combination of high plasma concentrations of AA and BDI, or BDI alone, causes oxidative damage to lipids and proteins in vivo.

Pneumonectomy for chronic infection is a high-risk procedure.

BACKGROUND: The purpose of this study was to estimate operative risk, and to identify indicators of adverse prognosis, in patients undergoing pneumonectomy for chronic infection. METHODS: Twenty-five patients aged 41 +/- 15 years underwent pneumonectomy (three completions) for chronic infection: sequelae of tuberculosis, 15; cystic bronchiectasis, 9; and radiation pneumonitis, 1. Eight patients had aspergilloma (7 after tuberculosis, 1 with radiation pneumonitis). RESULTS: Operative mortality was 4%. Operative blood loss was estimated at 1,983 +/- 1,424 mL, ranging from 150 to 5,600 mL. A single patient required reexploration. Eight patients (32%) had empyema, and a further 3 (12%) had bronchopleural fistula; thoracoplasty was required for 10 (40%). Sequelae of tuberculosis heralded increased operative bleeding (t = 2.884; p < 0.005). Incidence of empyema or bronchopleural fistula was increased in patients with sequelae of tuberculosis (chi 2 = 3.896; p < 0.05), patients with aspergilloma (chi 2 = 4.588; p < 0.05), patients in whom the parenchymal cavities were entered (chi 2 = 11.5; p < 0.001), and those in whom blood loss was in excess of 1,000 mL (chi 2 = 4.911; p < 0.05). CONCLUSIONS: We conclude that pneumonectomy is a high-risk procedure, especially in patients with sequelae of tuberculosis.

Tracheobronchial lacerations after intubation and tracheostomy.

BACKGROUND: Although long-term complications of intubation and tracheostomy are well documented, little has been reported on acute complications of airway access techniques. METHODS: Fourteen patients (1 male and 13 female patients) aged 15 to 80 years presented with tracheobronchial lacerations after single-lumen intubation (n = 9), double-lumen intubation (n = 1), or tracheostomy (n = 4). RESULTS: A left bronchial laceration after double-lumen intubation was discovered and repaired intraoperatively. A tracheal laceration after single-lumen intubation was recognized during induction of anesthesia. The remaining 12 were diagnosed within 6 to 126 hours (median, 24 hours) after injury. All patients had mediastinal and subcutaneous emphysema. At endoscopy, 12 injuries were located in the thoracic trachea and 1 in the cervical trachea. Twelve underwent primary repair through a right thoracotomy (n = 11) or left cervicotomy (n = 1), and 1 was treated conservatively. Two patients with tracheostomy injury died postoperatively. All repairs healed well but one. The latter was performed 5 days after the injury; a dehiscence occurred, but healed spontaneously. CONCLUSIONS: We conclude that prognosis of tracheal lacerations depends both on the general health of the patient and on the rapidity of diagnosis and treatment.

Evaluation of the sonographic features of malignant breast masses.

Breast sonography is a common technique in the assessment of breast masses. By this modality 114 patients (age 23-75 years) with breast masses were studied and 107 of them were suspected to have malignancy. The diagnosis was based on common sonographic features which included wall contour, echogenicity, echo pattern, posterior-attenuating shadow and lesion length-to-width ratio. Eighty-four and seven-tenths percents of the masses had jagged wall contour, 84.7% were echo-poor, and 76.6% had a heterogenous echo pattern. Sixty-five and eighty-tenths percent had posterior-attenuating shadows. Eighty-two and nine-tenths percent were spherically shaped or anteroposteriorly elongated. Using these features, the positive detection rate for malignancy was 91.2%. In conclusion, sonographic diagnosis of breast malignancies can be used in the assessment of breast masses.

Bronchogenic cancer in the elderly: operative risk and long-term prognosis.

Surgery for bronchogenic cancer raises the question of benefit to elderly patients. The present study reviews a cohort of 223 patients aged 70 years and more (range: 70-84), who underwent thoracotomy for pulmonary malignancy over a 10-year period. The aim of the study was to evaluate both operative risk and 5-year survival. Medical history was negative in 29% of the patients; 26% had a history of cardio-vascular disease, and 19% had a history of malignancy in complete remission. Tumor histology was squamous-cell carcinoma for 70.4%, adenocarcinoma for 24.2%, large-cell carcinoma for 3.6%, and small-cell carcinoma for 1.3% of the patients. 48.4% of patients were in stage I, 17.2% in stage II, and 30.3% in stage III. Exploratory thoracotomy was carried out in 5.8% of patients. A resection was achieved in 210 patients (pneumonectomy in 28.5%, lobectomy in 71.5%). Operative mortality was 7.2% for the whole series, 10% after pneumonectomy and 6.6% after lobectomy. Mortality was similar below and above 75 years. Overall 5-year survival was 32.9% (45.7% for stage I, 36.3% for stage II, and 13.8% for stage III). Survival was not influenced by age, symptomatic or asymptomatic presentation, medical history, and in particular not by history of malignant disease. Although operative mortality is slightly increased when compared to younger patients, long-term results legitimize surgery for bronchogenic cancer in the elderly.

Human suction blister interstitial fluid prevents metal ion-dependent oxidation of low density lipoprotein by macrophages and in cell-free systems.

LDL in the circulation is well protected against oxidation by the highly efficient antioxidant defense mechanisms of human plasma. LDL oxidation contributing to atherosclerosis, therefore, has been hypothesized to take place in the interstitial fluid of the arterial wall. We investigated the antioxidant composition and the capacity to inhibit LDL oxidation of human suction blister interstitial fluid (SBIF), a suitable representative of interstitial fluid. We found that the concentrations in SBIF of the aqueous small-molecule antioxidants ascorbate and urate were, respectively, significantly higher (P < 0.05) and identical to plasma concentrations. In contrast, lipoprotein-associated lipids and lipid-soluble antioxidants (alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene) were present at only 8-23% of the concentrations in plasma. No lipid hydroperoxides could be detected ( < 5 nM) in either fluid. The capacity of serum and SBIF to protect LDL from oxidation was investigated in three metal ion-dependent systems: copper, iron, and murine macrophages in Ham's F-10 medium. In all three systems, addition of > or = 6% (vol/vol) of either serum or SBIF inhibited LDL oxidation by > 90%. The concentration that inhibited macrophage-mediated LDL oxidation by 50% was as low as 0.3% serum and 0.7% SBIF. The enzymatic or physical removal of ascorbate or urate and other low molecular weight components did not affect the ability of either fluid to prevent LDL oxidation, and the high molecular weight fraction was as protective as whole serum or SBIF. These data demonstrate that both serum and SBIF very effectively protect LDL from metal ion-dependent oxidation, most probably because of a cumulative metal-binding effect of several proteins. Our data suggest that LDL in the interstitial fluid of the arterial wall is very unlikely to get modified by metal ion-mediated oxidation.

Decortication is a valuable option for late empyema after collapse therapy.

BACKGROUND: Infection of previous collapse therapy spaces may raise challenging problems. This study evaluated a conservative surgical approach based on decortication. METHODS: Since 1979, 28 patients (mean age, 60 +/- 6 years) have presented at an average of 37 +/- 7 years after artificial pneumothorax for tuberculosis. Diagnosis of empyema was made on follow-up in 12 patients and on symptoms in 16 patients. Mean vital capacity was 66% +/- 16% of normal. Microorganisms were isolated in 13 patients (Aspergillus fumigatus in 5, Mycobacterium tuberculosis in 4, anaerobes in 4). Decortication was made in 24 patients, associated with thoracoplasty in 4, and with partial lung resection in 2 patients. Thoracoplasty alone was performed in 2 patients, and 2 patients underwent an extrapleural pneumonectomy. RESULTS: Both extrapleural pneumonectomies were complicated with empyema requiring thoracoplasty, resulting in one postoperative death. Operative mortality after decortication was nil. Mean intraoperative blood loss during decortication was 1,830 +/- 1,310 mL. All patients were extubated within 24 hours, except 1 patient who was ventilator-dependent preoperatively. Prolonged air leaks were common (mean duration of drainage, 16 +/- 11 days), but ultimately sealed. Existence of symptoms was predictive of prolonged air leaks (p < 0.01). CONCLUSIONS: We conclude that decortication may provide a one-stage cure avoiding the hazards of extrapleural pneumonectomy; the nonfunctioning remaining lung may resolve the space problem.

Are bilobectomies acceptable procedures?

BACKGROUND: Controversy about operative morbidity and oncologic value of bilobectomy has led to a review of our experience over the past 12 years. METHODS: The charts of 112 patients (100 men and 12 women with a mean age of 63 years) were reviewed for operative mortality and morbidity and long-term survival. Survival of patients with stage I or stage II disease was compared with that of stage-matched and age-matched groups having right pneumonectomy. RESULTS: Four patients (3.5%) died postoperatively. Nonfatal complications occurred in 55 patients (49%); the most frequent problem was pleural space disease (34%). Survival studies focused on the 96 patients with nonsmall cell bronchogenic cancer (44 in stage I, 32 in stage II, and 20 in stage IIIA). The overall 5-year survival rate was 40%; the 5-year survival rate was similar for stage I and stage II (41% for stage I, 50% for stage II, and 17% for stage IIIA). The incidence of local recurrence was significantly increased after bilobectomy for stage I cancer (chi 2 = 5.066; p < 0.05) compared with pneumonectomy but did not affect 5-year survival. Local recurrence and survival were similar after bilobectomy and pneumonectomy in stage II. CONCLUSIONS: These data demonstrate an increased morbidity after bilobectomy. Survival studies demonstrate an increased risk of local recurrence in patients with stage I disease, which might be partly explained by understaging.

Late complication of a Greenfield filter associating caudal migration and perforation of the abdominal aorta by a ruptured strut.

We report the case of a 67-year-old woman who was admitted for surgical removal of a Greenfield filter that had been inserted 7 years before because of recurrent deep vein thrombosis associated with pulmonary embolism. This complication appeared on a plain abdominal radiogram that showed a 7 cm distal migration of the filter, a 30-degree angulation, and rupture of a strut at the level of the hub. Computed tomography, aortography, and ascending cavography demonstrated that the inferior vena cava was perforated by the struts and that the ruptured strut had penetrated the infrarenal aorta. As demonstrated by scanning electron microscopy, the fracture was due to a structural defect of the strut at its insertion point within the hub, with no sign of corrosion. Energy-dispersive radiography analysis failed to demonstrate impurity in the metal composition.

[Preoperative evaluation of cancers of the esophagus. Contribution of in vivo staining]. / Evaluation pré-opératoire des cancers de l'oesophage. Apport des colorations vitales.

OBJECTIVES: We assessed the effectiveness of a dye-endoscopy to detect inapparent multicentric carcinomas of the oesophagus. METHODS: The study included 95 patients scheduled for oesophagectomy. A lugol stain was applied to the oesophageal mucosa and any non-stained area was biopsied. The proximal oesophagus was reexamined on the pathology specimen obtained after oesophagectomy. RESULTS: Intramucosal epithelioma of the proximal oesophagus was found in 7 patients (7.4%) and severe dysplasia was seen in 3 (3.1%). Abnormal stains were seen in 33 patients including 9 with diffuse parakeratosis. There were 24 focal anomalies including 6 cases of intramucosal carcinoma, 3 severe dysplasias, 3 gastric metaplasias and 12 parakeratoses. One intramucosal epithelioma observed on the surgical specimen had not been detected by the staining technique. Overall sensitivity was 85.7% and specificity was 71.7%. Including focal anomalies only, specificity was 79.5%. CONCLUSION: Vital staining is a useful tool for pre-operative assessment of cancer of the oesophagus, in particular for superficial forms.

Ocular leukemia in King Abdulaziz University Hospital - Jeddah.

To the best of our knowledge, ocular leukemia has not been reported in Saudi Arabia. Seventy-two leukemia patients were seen in King Abdulaziz University Hospital in Jeddah over the last 10 years. Thirty-one of those patients had an ocular examination. Seventeen of these were found to have ocular abnormalities related to leukemia. Ten had acute lymphoblastic leukemia, four had acute myeloid leukemia and three had chronic myeloid leukemia. The retina and vitreous were involved in 12 of the ocular relapses, the anterior segment leukemic infiltrate in nine, glaucoma in five, opportunistic infection in four, cranial nerve palsies in three, proptosis and hypotony in two. Conjunctival hemorrhage, choroidal infiltrate and cataract were present in one relapse each. The optic nerve was involved in nine relapses, which is a serious condition that requires immediate intervention to save the patient's sight. Computed tomography (CT) scan of the brain and orbit was useful in differentiating between optic nerve infiltrate and papilledema. Most ocular relapses responded well to chemotherapy except relapses with optic nerve and anterior segment infiltrate, which required irradiation to save the patient's sight and prevent further relapses. In conclusion, the presented data have shown that ocular leukemia is not rare and emphasizes the importance of early ophthalmologic examination and radiation.