Optimization of the spherical integrity for sustained-release alginate microcarriers-encapsulated doxorubicin by the Taguchi method.

This study aimed to develop biodegradable calcium alginate microcarriers with uniform particle size and spherical integrity for sustained-release targeting transarterial chemoembolization. To determine related parameters including the ratio of cross-linking volume (sodium alginate: CaCl2), concentrations of sodium alginate and CaCl2 solutions, collection distance, flow rate, stirring speed, syringe needle diameter and hardening time to fabricate the microcarriers, the Taguchi method was applied. Using different conditions, a total of 18 groups were prepared. The average size of microspheres from different groups was estimated as ~ 2 mm (range 1.1 to 1.6 mm). Signal-to-noise ratio analysis showed the optimal spherical integrity (F1) achieved when the above parameters were designed as 0.1, 2.5 wt%, 6 wt%, 8 cm, 30 mL/h, 150 rpm, 0.25 mm and 2 h, respectively. The best (F1), middle (F2) and worst (F3) groups were used for further experiments. Fourier-transform infrared spectroscopy spectrum showed that F1, F2 and F3 conformations were distinct from original sodium alginate. Drug-loaded calcium alginate microcarriers demonstrated rougher surfaces compared to microspheres without drug under transmission electron microscopy. Compared to pH 7.4, swelling rates in PBS were decreased at pH 6.5. Encapsulation and loaded efficiencies of the Dox-loaded microcarriers were estimated as ~ 40.617% and ~ 3.517%. In vitro experiments indicated that the F1 Dox-loaded microcarriers provide a well sustained-release efficacy for about two weeks at 37 °C in PBS. Treatments of calcium alginate microcarriers without the Dox in two distinct hepatocellular carcinoma-derived cell lines, Huh-7 and Hep-3B, indicated that these microcarriers were non-toxic. The Dox-loaded microcarriers displayed sustained-release capacity and reduced cell viabilities to ~ 30% in both cell lines on Day 12.

Haemoperfusion treatment in pigs experimentally intoxicated by paraquat.

1. Because of their similarity in renal morphology and physiology to humans, domestic pigs (gilts, 70 kg) were bolus treated by intramuscular injection of 74, 17, and 6 mg kg-1 and by oral loading (70 mg kg-1 n = 4) of paraquat. The concentration peak of plasma paraquat was reached at 1.5 - 2.5 h. Renal clearance of paraquat rose to its maximum at 5-6 h after intoxication and then sharply decreased indicating renal failure. All the intoxicated pigs died. 2. An additional 10 gilts were also orally treated with 70 mg kg-1 paraquat but received haemoperfusion from 2 h post intoxication for either 2 h (n = 6) or 6 h (n = 4). The 2 h haemoperfusion resulted in a 5.1% toxin removal but failed to save any of six poisoned pigs. Prolonged 6 h haemoperfusion successfully rescued three out of four intoxicated pigs. 3. The plasma paraquat concentrations of the three surviving pigs were above 2 mg l-1 at 10 h post intoxication. This level is not only similar to those of untreated animals that died later, but also well beyond the suggested limit for survival of poisoned patients. 4. Pigs proved to be a good animal model for studies in paraquat poisoning and/or haemoperfusion. It is also suggested that early haemoperfusion is effective in treating paraquat poisoning even in very severe cases due to its possible detoxicating effect in addition to toxin removal.

A study of infrared thermographic assessment of liquid nitrogen cryotherapy.

OBJECTIVE: To assess whether infrared thermography can accurately predict the area of soft tissue necrosis that results from liquid nitrogen cryoprobe therapy. STUDY DESIGN: Eight rats received cryosurgery on the shaved abdomen with a liquid nitrogen cryoprobe in a triple-freeze technique. The therapy was monitored with infrared thermography and thermocouple probes. The temperature reached was correlated with the area of tissue necrosis found on histologic examination at sacrifice 1 week after the cryotreatment. A parallel study was carried out on pieces on beefsteak to assess the depth and shape of freeze. RESULTS: The -20 degrees C isotherm, which is felt to correspond to the cell lethal zone, occupied the inner 70% of the area of the iceball produced. Histologically, the -20 degrees C isotherm corresponded well to the area of tissue necrosis. In depth, the iceball takes on a semicircular shape. CONCLUSIONS: Infrared tomography is expensive to use clinically and cannot be readily used in the oral cavity. However, this study does show that one can clinically estimate that the inner 70% of the area of an iceball produced by liquid nitrogen on soft tissues will ultimately undergo necrosis.

Feasibility of Meckel's scan after RBC gastrointestinal bleeding study using in-vitro labeling technique.

The authors report a successful Meckel's scan performed 26 hours after a labeled RBC study using a commercial in-vitro labeling kit, UltraTag (Mallinckrodt Medical, Inc., St. Louis, MO). No abnormal alteration of Tc-99m distribution was observed as would be seen if an in-vivo RBC labeling technique was used. This case demonstrates that it is feasible to perform an in-vitro labeled RBC study for acute gastrointestinal bleeding in pediatric patients and to follow-up with a Meckel's scan if it is necessary for diagnostic confirmation.

Use of technetium-99m sulfur colloid to evaluate changes in reticuloendothelial function in dogs with experimentally induced chronic biliary cirrhosis and portosystemic shunting.

Technetium-99m sulfur colloid scintigraphy was used to study alterations of reticuloendothelial function in 7 dogs with experimentally induced biliary cirrhosis and portosystemic shunting. Scintigraphic studies were performed before and 6 weeks after common bile duct ligation. Radiocolloid plasma clearance rate was determined by measuring activity in plasma samples and by analyzing the rate of liver uptake on dynamic scintigraphic image sequences. Percentage of uptake in the liver, spleen, and lungs, as well as the ratio of hepatic-to-extrahepatic uptake, was determined from static equilibrium images. Relative to preoperative values, there were significant decreases in plasma clearance rate, percentage of liver uptake, and ratio of hepatic-to-extrahepatic uptake and significant increases in percentage of spleen and lung uptake on postoperative studies. The mechanism of technetium-99m-labeled sulfur colloid extraction by the liver is different from that of other radiocolloids; it does not require active phagocytosis or pinocytosis. Thus, liver uptake of this tracer principally reflects effective liver blood flow. Portosystemic shunting was documented in these dogs at the time of the postoperative radiocolloid scans, and we believed was responsible for the decrease in liver reticuloendothelial activity. Possible mechanisms for the increased splenic and pulmonary reticuloendothelial activities are discussed.

Technetium-99m-MDP uptake in thyroid cartilage in invasive squamous-cell laryngeal carcinoma.

A 36-yr-old male with a past history of invasive squamous-cell carcinoma of the larynx underwent 99mTc-MDP scintigraphy for the evaluation of lower back pain. The scan findings were unremarkable except for markedly and uniformly increased tracer uptake in the region of the thyroid cartilage, suggesting calcification and/or tumor invasion. Confirmation of significant pathology was obtained on tissue examination from a subsequent total laryngectomy demonstrating inflammatory infiltration and perichondrial invasion of the thyroid cartilage by carcinoma.

A count-based radionuclide method for volume quantitation using conjugate imaging and an external reference source: theoretical consideration and phantom study.

UNLABELLED: A count-based method was developed for ventricular volume determination during multigated equilibrium cardiac blood-pool imaging (MUGA). METHODS: Two sets of conjugate images of the volume were obtained, one with an external reference overlying the volume and the other without. The reference has known activity and dimension. The ratio of the geometric mean count rates over a pixel obtained from these two conjugate images, Ratio(geo), and the ratio of the specific activity in the reference to that in the volume, Ratio(ext), were used to calculate the length of the volume over that pixel perpendicular to the camera face, H, as a function of the length of the reference source, R, and the attenuation coefficient, ub, of the volume: [formula: see text] Based on H, the volume is then calculated. This method corrects for attenuation directly and determines the volume explicitly. To validate this method, phantom studies are carried out with known volumes of 99mTc containing saline solutions in situations of variable amount of attenuating medium and background activity. RESULTS: In all cases, the calculated volume agrees closely with the actual volume. CONCLUSION: This is an accurate method of volume quantitation that is well suited for determining ventricular volume during MUGA studies.

Tc-99m sestamibi myocardial imaging at rest for evaluation of cocaine-induced myocardial ischemia and infarction.

Many clinical cases of cocaine-induced myocardial infarction have been reported in the literature. Of the reported cases, patients tend to be young (in the third decade of life), chronic abusers with myocardial infarction typically involving the anterior left ventricular wall. This case report demonstrates the usefulness of two-phase (symptomatic and asymptomatic) Tc-99m sestamibi myocardial imaging at rest for definitive diagnosis of cocaine-induced myocardial ischemia and infarction.

Effect of stannous pyrophosphate red blood cell gastrointestinal bleeding scan on subsequent Meckel's scan.

Both labeled RBC and Meckel's scans have been used to evaluate pediatric patients with gastrointestinal bleeding, sometimes sequentially in the same patient. Particularly in infants, from whom withdrawal of sufficient blood for in vitro RBC labeling is often not possible, in vivo labeling with stannous pyrophosphate is used. However, prior administration of stannous-containing agents is known to alter the in vivo distribution of Tc-99m pertechnetate and to interfere with the subsequent Meckel's scan. The authors report on a Meckel's scan performed on an infant 1 week after a GI bleeding study with Tc-99m and stannous pyrophosphate. The Meckel's scan shows abnormal tracer distribution with absent gastric uptake, rendering the scan uninterpretable. In pediatric patients with gastrointestinal bleeding, a Meckel's scan should be done before labeled RBC imaging.

Comparison of shunt fraction estimation using transcolonic iodine-123-iodoamphetamine and technetium-99m-pertechnetate in a group of dogs with experimentally-induced chronic biliary cirrhosis.

Portosystemic shunt fraction estimation using transcolonic iodine-123-iodoamphetamine (IMP) has been previously validated relative to portal vein macroaggregated albumin injections using an experimental model of cirrhosis. Transcolonic technetium-99m-pertechnetate (TcO4-) has been proposed as an alternative tracer to IMP to study portal circulation in cirrhotic patients. We compared shunt fraction estimates from paired transcolonic IMP and TcO4- studies performed on a group of dogs before and after common bile duct ligation surgery. Pertechnetate over-estimated shunt fraction in 6/7 postoperative studies relative to IMP. A good correlation between the two methods was demonstrated, however, the slope of the regression line was substantially less than 1.0 with TcO4- values reaching 100% at IMP shunt values of approximately 60%. This apparent inability to accurately assess high shunt flows may limit the quantitative aspects of TcO4- studies on patients with severe portosystemic shunting.

A comparison of carbon dioxide laser, liquid nitrogen cryosurgery, and scalpel wounds in healing.

With the carbon dioxide surgical laser, the liquid nitrogen cryoprobe, and the scalpel, wounds were created on the shaved abdomen of 24 rats, and the patterns of healing were studied. The laser wounds were the first to epithelialize, followed by the scalpel wounds, with the cryosurgery wounds the slowest to epithelialize. The results were confirmed histologically.

Use of transcolonic 99mtechnetium-pertechnetate as a screening test for portosystemic shunts in dogs.

99mTechnetium-pertechnetate, when administered in high concentration into the colon, is rapidly absorbed across the colonic mucosa and results in a nuclear angiogram of the portal circulation. In normal dogs, a series of dynamic lateral scintigraphic images of the abdomen resulted in sequential visualization of the portal vein, liver, and several seconds later, the heart and lungs. In contrast, studies performed in 9 dogs with surgically confirmed portosystemic shunts demonstrated a different pattern of distribution, with heart and lung activity occurring before liver activity. In several cases, the aberrant shunt vessels could be identified. Studies were easy to perform, were well tolerated, and required no computer processing for interpretation.

Portasystemic shunt fraction quantification using transrectal administration of iodine-123 iodoamphetamine in dogs with chronic bile duct ligation and after propranolol administration.

Following transrectal administration, 123I iodoamphetamine (IMP) has been shown in both animal and patient studies to be capable of detecting the presence of portasystemic shunting (PSS). However, the ability of this method to actually quantitate PSS in the presence of cirrhosis and propranolol has not been demonstrated. We studied nine dogs with hitologically proven cirrhosis induced by chronic bile duct ligation. After intravenous injection of propranolol, PSS were measured with both the IMP method and the standard of portal vein infusion of 99mTc macroaggregated albumin (MAA) given through a mesenteric vein catheter. Based on linear regression, a close relationship was seen, given by the equation: MAA = IMP 0.9 + 0.035, with correlation coefficient of 0.99. Thus, in dogs with cirrhosis secondary to chronic bile duct ligation and after propranolol administration, PSS can be quantitated with the transrectal IMP method.

Studies in tooth crown temperature gradients with the use of infrared thermography.

With the use of an infrared thermographic camera; temperature patterns over the crowns of teeth were recorded. The temperature of upper incisor teeth decreased from gingival margin to incisal edge by approximately 2.5 degrees C. Vital and nonvital teeth were the same temperature at rest, but after cooling with cold air, nonvital teeth were slower to rewarm than vital teeth. The infrared thermographic camera could provide a method of testing tooth vitality based on blood supply rather than nerve supply.

Infrared thermography in oral and maxillofacial surgery.

A highly sensitive infrared thermographic camera was evaluated in a variety of physiologic and pathologic conditions associated with the head and neck. Although it may have clinical applications, particularly in the field of facial pain and the temporomandibular joint, such wide variations in normal values were noted that any standardization was extremely difficult.

Portasystemic shunt fraction quantification with colonic iodine-123 iodoamphetamine.

Portasystemic shunting was quantified in dogs with [123I]iodoamphetamine (IMP) administered transrectally into the colon and monitored externally with a gamma camera. IMP was absorbed rapidly and unchanged from the colon. After direct injection into the portal vein, IMP was almost completely extracted by the liver on the first pass, and the washout half-life was approximately 60 min. Based on these kinetic data, computer simulation of this biologic system was carried out. Errors associated with simplified models are calculated. The simplest model with insignificant error, which assumed that the tracer behaved like microspheres, was used to quantitate portasystemic shunt fraction in animals with surgically created shunts. Results were compared with the standard of 99mTc-labeled macroaggregated albumin infused into a branch of inferior mesenteric vein. For shunt fractions ranging from 0 to 100%, an excellent correlation was seen, indicating that this approach is potentially a simple, noninvasive method of portasystemic shunt fraction quantification.

Rupture of a spontaneous aortoduodenal fistula visualized with Tc-RBC scintigraphy.

We present what we believe is the first reported case of a spontaneous aortoduodenal fistula, with massive rupture into the duodenum during the performance of a radionuclide study of gastrointestinal bleeding. Our experience suggests that nuclear scintigraphy with labeled red blood cells can help in the diagnosis of this disorder by demonstrating both the presence of an abdominal aortic aneurysm and bleeding in the gut.

Brain tumor evaluation using Rb-82 and positron emission tomography.

Positron emission tomography of the brain with 75-sec rubidium-82 obtained from a portable generator (25-day Sr-82 leads to Rb-82) was used to evaluate the integrity of the blood-brain barrier (BBB) in patients with brain tumors. Rubidium is normally excluded from the central nervous system by the intact BBB, but when the BBB is disrupted by a tumor. Rb enters and pools in the extravascular spaces of the central nervous system. Since Rb is also rapidly cleared from the blood, a high tissue-to-blood ratio of the Rb-82 tracer is achieved in regions of BBB disruption after intravenous injection. With dynamic positron emission tomographic imaging, the extravasation of the Rb tracer can be evaluated independent of the intravascular Rb concentration, and very small changes in the BBB permeability can be detected. The results of our studies in eight patients show that this technique is a promising method for evaluation of the BBB integrity in brain-tumor patients.U

Evaluation of blood-brain barrier permeability changes in rhesus monkeys and man using 82Rb and positron emission tomography.

Dynamic positron tomography of the brain with 82 Rb, obtained from a portable generator [82Sr (25 days) - 82 Rb (76 sec)], provides a means of studying blood-brain barrier (BBB) permeability in physiological and clinical investigations. The BBB in rhesus monkeys was opened unilaterally be intracarotid infusion of 3 M urea. This osmotic barrier opening allowed entry into the brain of intravenously administered rubidium chloride. The BBB opening was demonstrated noninvasively using 82Rb and positron emission tomography and corroborated by the accumulation of 86Rb in tissue samples. Positron emission tomography studies can be repeated every 5 min and indicate that dynamic tomography or static imaging can be used to study BBB permeability changes induced by a wide variety of noxious stimuli. Brain tumors in human subjects are readily detected because of the usual BBB permeability disruption in and around the tumors.