Encapsulation capacity and natural payload delivery of an anticancer drug from boron nitride nanotube.

The behavior of confined anticancer carboplatin (CPT) molecules in a single (10, 10) boron nitride nanotube (BNNT) was studied by means of molecular dynamics simulations. Our study revealed a very large storage capacity of BNNT. Analysis of the energy profiles depending on the number of confined molecules, and on their spatial organization allowed us to quantify the ability of BNNT to vectorize CPT. Indeed, BNNT despite its small radius presented a large inner volume that favored stable encapsulation of multiple active anticancer molecules. Moreover, in our molecular dynamics simulations, the empty BNNT and the BNNT filled with CPT diffused spontaneously to the cell membrane and were able to passively enter inside lipid bilayers by a lipid-assisted mechanism. This property has been used to deliver naturally anticancer drugs to cellular targets. Using this enhanced drug delivery system, we have provided a definitive solution to the problem of drug release and have thus opened up a new way of targeting cancer cells. Indeed, regardless of the mode of action of the platinum complex towards the cell, the delivery of the drug on site should limit the side effects of the drug.

F-18 FDG PET identification of right atrium metastasis from a vesical carcinoma.

Fluorodeoxyglucose (FDG) positron emission tomography (PET) has been shown to be useful in the diagnosis and staging of various malignancies. The main advantage of PET is its high sensitivity in identifying malignancies at an early stage. The authors present a patient in whom transthoracic echography and MRI revealed a right atrial mass. The diagnosis was difficult between tumor and thrombus, but PET imaging correctly suggested a malignant tumor.

[Combined bipolar radiofrequency and cementoplasty of bone metastases]. / Radiofréquence bipolaire et cimentoplastie dans le traitement des métastases osseuses.

Bone metastases are the most common cause of pain in cancer patients. Pain management in cancer patients, often revealing the disease and always present at advanced stages, is an important and difficult task. Pain is not always properly controlled by high doses of specific medication, radiation therapy or chemotherapy. When these therapies do not provide adequate pain relief, percutaneous neurolysis, infiltrations, alcoholizations and cementoplasty may be considered. More recently RF ablation has been proposed. On weight-bearing bones, RF can be combined with acrylic cement injection. The authors present here this very effective new technique which is complementary to classical pain management techniques.

[Pain management in bone metastasis of pulmonary origin: new interventional and metabolic techniques]. / Nouvelles techniques interventionnelles et métaboliques dans la prise en charge des métastases osseuses.

Invasion of bone by a metastatic lesion is the most common cause of pain in cancer patients. Pain management in these patients is an important and difficult task. The pain is not always properly controlled by high doses of specific medication, radiation therapy or chemotherapy. When these therapies do not provide adequate pain relief, percutaneous vertebroplasty, cementoplasty, radiofrequency ablation and internal radiotherapy appear to be elegant and efficient complementary alternative pain control methods.

Ultrastructural apoptotic lesions induced in bone marrow after neptunium-237 contamination.

This study describes the ultrastructure of lesions induced by neptunium-237 (237Np), a by-product of uranium in nuclear reactors, in the bone marrow. A group of rats were given a single injection of 237Np-nitrate solution in order to observe the acute toxicity effects of this actinide. Electron microscopy was used to describe the different lesions. Observations included the swelling of the cell membrane, nuclear membrane lyses, abnormal chromatin condensation or nucleus convolution. These ultrastructural alterations of the nucleus and the cellular membrane appeared shortly after treatment. This study demonstrates the toxic effects of neptunium and its implication in the induction of apoptosis in bone marrow.

Ultrastructural lesions induced by neptunium-237: apoptosis or necrosis?

In this study, we are concerned with the 237 isotope of neptunium (237Np), which is a by-product of uranium in nuclear reactors. To study ultrastructural lesions induced by this element, a group of rats were injected with a solution of 237Np-nitrate once a day for 14 weeks. Lesions observed in liver and kidney are described using electron microscopy. Ultrastructural alterations of cellular membranes and intracellular organelles demonstrated the existence of neptunium toxicity. This toxicity was characterized by various lesions, such as cytoplasmic clarification, disappearance of mitochondrial cristae, swollen mitochondria, abnormal condensation of nuclear chromatin, and nuclear fragmentations. This study demonstrated the probable induction of apoptosis by neptunium both in liver and kidneys.

In vivo sequential study of skeletal muscle capillary permeability in diabetic rats: effect of anthocyanosides.

Alterations in the capillary filtration of macromolecules are well documented in diabetic patients and experimental diabetes. Various flavonoids including anthocyanosides and ginkgo biloba extracts have been shown to be effective against experimentally induced capillary hyperfiltration. The aim of the present study was to test the effects of anthocyanosides on capillary filtration in diabetic rats. For this purpose, we have validated the use of our previously described in vivo method for measurement of the capillary filtration of albumin (CFA) in rats. Male Wistar rats with streptozotocin (STZ)-induced diabetes were randomized in 3 groups to receive either ginkgo biloba (group A), Vaccinium myrtillus (group B), or no treatment (group C). The isotopic test of CFA consisted of intravenously injecting 99mtechnetium-labeled albumin, inducing venous compression on a hindquarter, and measuring radioactivity externally on the limb before, during, and after removal of venous compression. After removal of the tourniquet, the radioactivity curve decreased. Interstitial albumin retention (AR) and the ratio of the amplitudes of the low- and high-frequency peaks (LF/HF ratio), an index of lymphatic function obtained by the fast Fourier transform of the last part of the radioactivity curve, were calculated. In STZ-treated animals, the isotopic test was performed at a mean age of 97 days (time 1) and after 6 weeks (time 2) and 12 weeks (time 3) of treatment, ie, 6 and 12 weeks after time 1. At time 1, AR was significantly higher in the 3 diabetic groups than in the control rats, without a significant difference between these groups. In group B, AR decreased significantly (P = .015) at times 2 and 3. In group C, AR increased significantly (P < .0005) from time 1 to time 3. In group A, AR increased slightly (NS) between time 1 and time 3. In groups A and C, the LF/HF ratio significantly increased with time (P < .0005) and the levels at time 3 were significantly higher versus control rats (P < .0001). In group B, the LF/HF ratio remained unchanged from time 1 to time 3 and similar to the values found in the control rats. In conclusion, these data show that (1) this new in vivo noninvasive method can be used to study CFA in skeletal muscle in diabetic rats, (2) it is reproducible and may be repeated over several months to evaluate spontaneous microcirculatory changes, and (3) anthocyanosides appear to be effective in preventing the increase in CFA and the failure of lymphatic uptake of interstitial albumin in diabetic animals.

The value of combined radionuclide and magnetic resonance imaging in the diagnosis and conservative management of minimal or localized osteomyelitis of the foot in diabetic patients.

Early diagnosis of osteomyelitis is helpful for a successful conservative treatment. The value of bone scanning combined with granulocytes labeled with hexamethylpropylene amine oxime (HMPAO) granulocyte-Tc99m (GN) radionuclide imaging (combined [RI]) with magnetic resonance imaging (MRI) for the diagnosis of osteomyelitis was assessed in 24 diabetic patients with foot ulcers. Evidence of osteomyelitis was based on the presence of at least one of the following criteria: (1) clinical bone involvement, (2) radiological bone involvement, (3) both positive combined RI and MRI, and (4) evidence of clinical bone involvement during the follow-up period. Thirteen patients had osteomyelitis. Seven patients had clinical bone involvement (sensitivity, 54%), five had radiological bone involvement (sensitivity, 38%), and 10 had positive combined RI for osteomyelitis (sensitivity, 77%). MRI demonstrated a higher sensitivity (100%). The specificity for combined RI and MRI was 82%. These results lead to a new diagnostic strategy for the early detection of minimal or localized osteomyelitis to avoid amputations. MRI is most appropriate following a negative x-ray in determining whether to treat osteomyelitis, since a negative MRI result rules out osteomyelitis. Antibiotic therapy should be used in the case of a positive MRI result, but Charcot joint disease can lead to false-positive MRI results. In this case, combined RI should be performed.

Value of quantitative radionuclide bone scanning in the diagnosis of sacroiliac joint syndrome in 32 patients with low back pain.

A prospective study was performed to compare the results of quantitative radionuclide bone scanning with those of sacroiliac joint anesthetic block in patients with unilateral low back pain. Thirty-four subjects, forming the control group, underwent quantitative radionuclide bone scanning of the sacroiliac joints. The normal values in sacroiliac uptake difference were taken to be between -1.7% and +6.2%. Thirty-two patients with chronic unilateral low back pain underwent sacroiliac bone scanning and sacroiliac joint block. Six of the seven patients with increased uptake > 6.2% on the painful side had at least 75% pain reduction in response to the block. The sensitivity, specificity, and positive and negative predictive values of the quantitative bone scanning in the unilateral mechanical sacroiliac joint syndrome were 46.1%, 89.5%, 85.7%, and 72%, respectively.

Secondary hyperparathyroidism: detection with I-123-Tc-99m-Sestamibi subtraction scintigraphy versus US.

PURPOSE: To compare iodine-123-technetium-99m-sestamibi subtraction scintigraphy with ultrasonography (US) for detection of parathyroid abnormalities in uremic patients with secondary hyperparathyroidism. MATERIALS AND METHODS: Fourteen adult uremic patients with severe secondary hyperparathyroidism underwent subtraction scintigraphy before total or subtotal parathyroidectomy. Subtraction scintigrams were acquired with a double-energy-window technique. US was performed with high-frequency transducers and standard methods. RESULTS: 1-123-Tc-99m-sestamibi subtraction scintigraphy correctly demonstrated 41 of 50 surgically confirmed enlarged parathyroids; US demonstrated 27. Sensitivity for detection of hyperplastic glands was 82% for scintigraphy and 54% for US. Scintigrams were correct in seven patients, and US scans were correct in five. Scintigraphy demonstrated all four enlarged parathyroids in six of 12 patients who were to undergo first surgery, whereas US demonstrated all four enlarged glands in three of the 12 patients. Gland weight was correlated with likelihood of detection with either method. Glands undetected at scintigraphy were significantly (P < .01) smaller (mean weight, 257 mg) than those undetected at US (mean weight, 467 mg). CONCLUSION: I-123-Tc-99m-sestamibi subtraction scintigraphy is efficient for detection of enlarged parathyroid glands in uremic patients with secondary hyperparathyroidism and is more sensitive than US.

Subcellular localization of neptunium-237 in lung and kidney after intratracheal administration in the rat: an ultrastructural and microanalytical study.

Chronic intratracheal administration of 237Np to rate was performed during 6 weeks. The total dose administered was 45.8 kBq. Two methods, electron microscopy and electron probe X-ray microanalysis, were used to determine the intracellular sites of localization of 237Np. Clusters of dense granules were observed in nuclei of pneumocytes and proximal tubular cells of the kidneys. These clusters have been shown to contain neptunium associated with phosphorus, sulfur and calcium. Alterations of nuclei and ultrastructural cytoplasmic lesions were observed. The absorbed doses in lungs and kidneys were very low. These results suggest that the chemical toxicity of 237Np is more important than its radiological toxicity.

Implantable insulin pumps: diagnosis and management of decreased flow rates using radionuclide investigation.

The aim of this study was to develop a diagnostic procedure for pumping unit malfunction by radionuclide imaging (RI) and to validate the method by comparing the results with those obtained using more conventional methods. Fifteen radionuclide investigations were performed in 11 patients with intraperitoneal implantable insulin pumps. One mCi of 99 mTc in 1 ml isotonic sodium chloride was injected into the reservoir. The results based on catheter visualization and peritoneal accumulation were compared blindly to the efficacy of alkaline rinses and laparoscopic findings. In all RI stoppage cases except one alkaline rinses failed to restore flow. Where laparoscopy was performed, comparisons were concordant i.e. no outflow from the tip of the catheter. The RI images obtained were reproduced in vitro using a pump under normal flow conditions and complete proximal and distal catheter obstruction. RI is a safe, quick non invasive method which allows the location of the site of pump/catheter malfunction within a one step procedure and the prediction of the efficacy of sodium hydroxide rinses.

Intranuclear dense bodies after metal intoxication: a review of ultrastructural and microanalytical findings.

Abnormal intranuclear dense bodies are observed in several varieties of cells after intoxication by four varieties of metals: lead, bismuth, beryllium and neptumium. These inclusions have been studied by two microanalytical methods: Electron probe X-ray microanalysis (EPMA) and ion microscopy. A strong similarity has been observed in the ultrastructure of the dense bodies produced several weeks after beryllium and neptunium intoxication although there exists an important discrepancy between both elements concerning their physical, chemical and physico-chemical characteristics. Furthermore, these dense bodies are observed in the same varieties of cells (tubular proximal cells of kidneys, hepatocytes, pneumocytes). Intranuclear dense bodies produced by lead are also observed in the same types of cells, where they showed similar ultrastructure patterns as beryllium and neptunium inclusions but only after a long period, several years, after a chronic intoxication. The ultrastructure of the dense bodies produced by bismuth are clearly distinct from beryllium, neptunium or lead inclusions. Beryllium, neptunium and lead have been detected by EPMA or ion microscopy in the corresponding dense bodies although the real presence of bismuth remains to be confirmed in the nuclear dense bodies produced by this element.

Management of focal nodular hyperplasia and hepatocellular adenoma in young women: a series of 41 patients with clinical, radiological, and pathological correlations.

Preoperative distinction between focal nodular hyperplasia (FNH) that should be managed conservatively and hepatocellular adenoma (HA) that should be resected remains difficult. The result is controversial management of these patients. The aims of this study were to report the value of modern imaging procedures for noninvasive diagnosis of these lesions, to assess the value of intraoperative frozen section studies, and to propose a management strategy in those patients. Forty-one consecutive women with FNH (35 cases) or HA (6 cases) treated at our institution between 1985 and 1992 were studied. New imaging techniques, including enhanced magnetic resonance imaging (MRI) and color Doppler ultrasonography (US), were prospectively appraised in addition to usual techniques. Histological examination of surgical specimens was obtained in all cases. A sixfold increase in the number of patients with FNH was observed during this study, whereas the number of patients with HA did not change. FNHs were incidental US findings in 74% of the cases. The best imaging procedure in the diagnosis of FNH was enhanced MRI with a sensitivity of 70% and a specificity of 98%. Color Doppler US was a useful adjunct. Intraoperative frozen section studies were performed in 16 patients with 19 tumors with a sensitivity of 89% and a specificity of 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Intranuclear sites of Np 237 in mammalian cells: a study using electron microscopy and electron probe microanalysis.

Two methods, electron microscopy and wavelength dispersive electron probe microanalysis, were used to determine the intracellular sites and chemical form of concentrations of neptunium nitrate 237 after chronic intoxication by the intraperitoneal route in two organs in the rat known to concentrate this element (kidney, liver). Abnormal intranuclear formations in the form of clusters of dense granules containing neptunium, phosphorus, sulphur, and calcium were found in the nuclei of kidney proximal tubule cells and hepatocytes. These formations had a maximum diameter of the order of 2 microns and were located in the central part of the nucleus, away from the nucleolus and peripheral chromatin. Serious nuclear and cytoplasmic ultrastructural lesions are often associated in cells containing neptunium inclusions. The absorbed doses in the kidney and the liver were very low. A relationship between these abnormal intranuclear structures and the carcinogenic effect of neptunium remains to be clarified. This effect is related more probably to the chemical toxicity of Np 237.

The hot spot hepatobiliary scan in focal nodular hyperplasia.

A prospective study was performed on 14 patients with histologically proven focal nodular hyperplasia (FNH) using a hepatobiliary scan with trimethylbromoimino-diacetic acid (TBIDA) and a colloid scan with rhenium sulfur colloids. TBIDA uptake was relatively normal in the region of the tumor, but during the clearance phase 23/25 of the tumors were detected by a hot spot of radioactivity. Depending on the relative contrast achieved between the tumor and normal liver, this hot spot appeared early or later, but was always present at 60 min. In three tumors, a "doughnut" pattern was observed within the hot spot due to a central defect. Hypervascularization was observed during the perfusion phase in 76% of the tumoral sites and normal colloid uptake in only 64%. The detectability of FNH appears greater with TBIDA (92%) than with CT or MRI (84%). The high prevalence of hot spots may be due to careful technological conditions when obtaining hepatobiliary scans. Late images, overexposed films, multiple views and stimulation of gallbladder excretion increased tumor detectability. The hot spot sign may be a useful tool when combined with the results of other imaging modalities in the diagnosis of FNH. The peculiar pathology of FNH with fibrosis, hyperplastic hepatocytes and cholangiolar proliferation might explain this scintigraphic appearance.

Thyroid carcinoma with tracheal or esophageal involvement: limited or maximal surgery?

This retrospective study was undertaken to evaluate the prognosis of and to determine optimal therapy for thyroid carcinoma adhering to or invading the trachea or esophagus. In our series of 412 operated thyroid cancers, there were 45 patients including 20 with adherences to the trachea or esophagus that were dissected free by sharp dissection (group 1), six patients with invasion of the trachea or esophagus who underwent total resection followed by radioiodine and external-beam irradiation (group 2), and 19 patients with invasion of the trachea or esophagus that had been incompletely resected (group 3). There were no major complications. Survival or disease-free unrelated deaths were recorded in 80%, 100%, and 16% of patients in groups 1, 2, and 3, respectively. The three patients with anaplastic carcinoma in group 1 are free of disease 3, 6, and 7 years after operation, respectively. Combined with those in the literature, our data indicate that (1) adherences to the trachea or esophagus are not necessarily associated with poor prognosis and should be treated with aggressive surgery even in anaplastic carcinoma, (2) invasion of the trachea or esophagus must be treated whenever possible by total resection followed by radioiodine and external-beam irradiation, (3) a two-stage operation should be considered when optimal conditions are not available initially, and (4) cure may be obtained with complementary radioiodine and external-beam irradiation after incomplete resection of papillary carcinoma.