Image-guided laparoscopic pelvic lymph node dissection using stereo visual tracking free-hand laparoscopic ultrasound.

Laparoscopic pelvic lymph node dissection is a delicate operation because pelvic arteries, which should be located first to guide the dissection, are often concealed by tissues and cannot be identified in the endoscopic view. Consequently, arteries can be damaged if they are not located accurately. To improve dissection safety and efficiency, we have developed an image-guided navigation system to provide pelvic artery position information by registering a 3D artery model extracted from CT images to a 3D model reconstructed from free-hand laparoscopic ultrasound images. The ultrasound probe is tracked using a proposed stereo vision-based tracking strategy that can simplify the system and reduce setup time. The artery is segmented from 2D ultrasound images using a local phase-based snakes framework. The accuracy of the proposed navigation system was estimated in a phantom experiment (the TRE error was 1.58 ± 0.70 mm), and the feasibility of the proposed navigation system was confirmed in an animal experiment.

An AB block copolymer of oligo(methyl methacrylate) and poly(acrylic acid) for micellar delivery of hydrophobic drugs.

An AB block copolymer of oligo(methyl methacrylate) (oMMA) and poly(acrylic acid) (PAAc) has been synthesized. The block copolymer forms micelles in an aqueous medium, as confirmed by a fluorescence probe technique using pyrene. Doxorubicin hydrochloride was incorporated into the micelle and the release profile of doxorubicin hydrochloride was investigated. Slow and prolonged release of doxorubicin hydrochloride from the micelle was observed. The AB block copolymer micelle can be useful for prolonged mucosal drug delivery of hydrophobic drugs.

Optical and atomic force microscopy of an explanted AcrySof intraocular lens with glistenings.

PURPOSE: To assess the surface morphology and cause of glistenings in an explanted AcrySof intraocular lens (IOL). SETTING: Shakai Hoken Kobe Central Hospital, Kobe, Japan. METHODS: A 63-year-old Japanese man had implantation of an AcrySof IOL in the capsular bag. One month postoperatively, he had a neodymium:YAG laser capsulotomy for posterior capsule opacification, which changed the IOL's position in the capsular bag. A few months later, the patient developed disabling night glare from intralenticular glistenings and progressive hyperopic refractive error. The IOL was explanted and then analyzed by optical microscopy and atomic force microscopy (AFM). Laboratory analysis of control AcrySof IOLs kept in a balanced salt solution at steady room and body temperature for 2 months was also performed to evaluate the cause of the glistenings observed clinically. RESULTS: Optical microscopy showed that the explanted AcrySof IOL had several microvacuoles; no abnormalities were observed in the control AcrySof IOLs before or after folding at the room and body temperatures. The AFM analysis showed a significant change in the surface morphology of the explanted IOL, including vacuolar formations in the posterior surface as well as numerous anterior surface irregularities. No microvacuoles or surface morphology alterations were observed in the control AcrySof IOLs by AFM analysis. CONCLUSIONS: The glistenings in the explanted AcrySof IOL were likely caused by temperature changes and not mechanical stress from folding.

Glistening formation in an AcrySof lens initiated by spinodal decomposition of the polymer network by temperature change.

PURPOSE: To examine the effect of temperature change on the structural alteration and glistening formation in an AcrySof intraocular lens (IOL). SETTING: Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Kobe, Japan. METHODS: The equilibrium water content of a Wagon-Wheel-packaged AcrySof IOL was determined at various temperatures by the gravimetrical method. Alterations in the microscopic structure of the lens were analyzed in situ with a reflecting microscope without staining, while the temperature of the lens was changed at different rates. RESULTS: Microvacuoles of 1.0 to 20.0 microm formed in the bulk of a swollen AcrySof IOL as the temperature decreased. The morphology of the vacuoles was similar to that of glistening particles observed in vivo. The size and density of the glistening-like vacuoles varied depending on the magnitude and rate of the temperature decrease. The glistening-like vacuoles were imprinted in the bulk of the IOL during the preceding cooling process in aqueous humor. CONCLUSIONS: Glistenings formed in the bulk of an AcrySof IOL as the medium temperature decreased. The mechanism may involve spinodal decomposition of the swollen polymer network, which initiates the formation of microvacuoles consisting of water and loosely packed network chains.

Complications associated with endocapsular balloon implantation in rabbit eyes.

After phacoemulsifying the lens in six rabbit eyes through a 1.3 mm anterior capsule opening, we implanted a silicone balloon in the capsular bag and filled it with liquid silicone. The eyes were enucleated nine to 21 months postoperatively, embedded in paraffin, stained with toluidine blue, and examined by stereoscopic and light microscopy. We looked at the postoperative complications primarily. All balloons were securely fixated within the capsule. Surface wrinkles were observed in two balloons. The injected silicone remained transparent. None of the lens capsules was completely transparent, although all remained relatively clear. Retrocorneal membranes were produced in one eye in which the silicone leaked.

Rotation vector analysis of eye movement in three dimensions with an infrared CCD camera.

We have developed a new technique for analyzing the rotation vector of eye movement in three dimensions with an infrared CCD camera based on the following four assumptions; i) the eye rotates on a point; ii) the pupil edge is a circle; iii) the distance from the center of eye rotation to pupil circle remains unchanged despite the rotation; iv) the image of the eye by the CCD camera is projected onto a plane which is perpendicular to the camera axis. After taking digital images of voluntary circular eye movements, we first constructed a three-dimensional frame of reference fixed on the orbita of the subject wearing a goggle equipped with an infrared CCD camera, and determined the space coordinates of the center of eye rotation, the center of the pupil, and an iris freckle. We then took digital images of the eye movements during a saccade or vestibulo-ocular reflex (VOR) and analyzed the axis and angle of the eye movements by the trajectories of the center of the pupil and the iris freckle. Finally, Listing's plane of saccade and the gain and the phase of VOR were obtained. The suitability of this technique is examined.

Assessment of extensive surgery for locally advanced lung cancer. Safety and efficacy of induction therapy.

OBJECTIVE: Locally advanced lung cancer has a poor prognosis, despite extensive surgery conducted in an effort to improve survival. We evaluated the safety and efficacy of induction therapy prior to extensive surgery for locally advanced lung cancer. METHODS: Primary resection for lung cancer was done in 549 consecutive patients divided into three groups; 446 undergoing standard pulmonary resection (no extensive surgery), 87 undergoing extensive surgery without induction therapy, and 16 undergoing surgery after induction therapy. RESULTS: Morbidity was 23.5%, 28.6%, and 43.8%, respectively. The rate was significantly higher in the induction group compared with the no extensive surgery group (P < 0.05). Surgical mortality was 0.67%, 3.4%, and 6.3%, respectively. The difference was statistically significant between the no extensive surgery and extensive surgery groups (P < 0.02), and between the no extensive surgery and induction groups (P < 0.02). Hospital mortality was 2.2%, 9.2%, and 6.3%, respectively. The rates were significantly higher in the extensive surgery (P < 0.01) and induction (P < 0.05) groups compared to the no extensive surgery group. Five-year survival was 50.3% for the patients who received induction therapy, and 14.7% for the patients who did not receive induction therapy. CONCLUSIONS: Survival differences between the induction and non induction groups were not significant, but some patients with T3 or T4 disease may benefit from induction therapy. The high morbidity of induction treatment should be recognized, and strict candidate selection and careful postoperative care used to help prevent increased mortality.

A laser Raman spectroscopic study on the interaction of alkylmercury with thiol and sulfur-containing compounds.

The interaction of the methylmercury cation with sulfur compounds in aqueous solution at physiological pH was studied by laser Raman spectroscopy. Metal binding is shown to occur preferentially at the sulfhydryl group of sulfur compounds. Raman frequencies of S-Hg stretching of the one-to-one methylmercury-sulfhydryl or sulfur-containing complexes were observed at approximately 330 cm-1. There was no frequency shift when ligands were exchanged. However, the relative intensity (I S-Hg/I C-Hg) was different. The relative intensities of MeHg-thioglycerol, MeHg-cysteine and MeHg-2-mercaptobenzothiazole were 0.18, 0.43 and 0.62, respectively. Methyl-mercury shifted from combination states of lager relative intensity to ones of smaller relative intensity. These results may cast light on the distribution and excretion mechanisms of methylmercury in the human body.

Formation of poly(glucosyloxyethyl methacrylate)-concanavalin A complex and its glucose-sensitivity.

The complex formation between Concanavalin A (Con A) and a polymer having pendant glucose groups was studied in order to design a glucose-sensitive polymer. The polymer having pendant glucose (poly(glucosyloxyethyl methacrylate) or (poly(GEMA)) forms a complex with Con A in tris HCl buffer (pH = 7.5). The solution then becomes turbid due to the multiple associations between poly(GEMA) and Con A. When free glucose or mannose are added to the turbid solution, the solution becomes transparent again. However, the addition of galactose does not cause the solution to be transparent. This indicates that Con A prefers to form a complex with free glucose or mannose (but not galactose) rather than with the pendant glucose in poly(GEMA). Therefore, the complex between poly(GEMA) and Con A is expected to be glucose- and mannose-sensitive. The apparent dissociation constants of the complexes between saccharide (poly(GEMA), glucose, and mannose) and Con A were also determined by affinity electrophoresis.

Thymomas associated with pure red cell aplasia. Histologic and follow-up studies.

Seventeen cases of pure red cell aplasia (PRCA) with thymoma were studied clinically, histologically, and immunologically. Two cases were associated with myasthenia gravis (MG), and three with hypogammaglobulinemia. Coombs test and antinucleus antibody test were positive in five cases. All thymomas were spindle cell types, and the adjacent thymuses had no germinal center, but showed epithelial clusters frequently. All patients, except one whose tumor was unresectable, had thymo-thymomectomy. The operation was effective in six cases (37.5%), and the effects were not different between two operative procedures (simple and extended thymectomy). Myasthenic symptoms in two patients remitted after the operation, but effects on hypogammaglobulinemia were conincident with those on PRCA.

Scanning electron microscope study on the biodegradation of IOL and suturing materials.

The biodegradation of the IOLs (27 cases: mainly prepupillary lens with pupillary fixation, irido-capsular and angle supported lens and a J loop lens for posterior chamber lens) and suturing materials of four cases have been studied by Scanning Electron Microscope (SEM). The longest duration in the eye was 7.5 years and the shortest 0.3 year. The materials used for optics were PMMA with the exception of one case of glass. The materials for haptics were Nylon 6, Isot.PP, PMMA, PVDF, Polyimid and Pt-Ir. The suturing materials were Nylon 6 and Isot.PP. Nylon 6 degraded in the eye and Isot.PP degraded in the corneal tissue. But no biodegradation was observed in Isot.PP, PMMA, PVDF and Pt-Ir in the eye. In our investigations, biodegradation has some relationship to age (over 50 years old), duration (within 7.5 years) and inflammation of the eye, but ultimately biodegradation will depend on the individual situation. Degradation occurs most easily in the curved portion of Nylon 6.

[A case of paraganglioma in the posterior mediastinum].

A case of non-functioning aortico-sympathetic paraganglioma originating from left posterior mediastinum in a 34-year-old man is reported. He was found to have an abnormal shadow on the chest X-ray of an asymptomatic. His blood pressure and serological examination were within normal range on admission to our hospital. At thoracotomy a bronze 5 x 5 x 5 cm mass was recognized at the costovertebral sulcus related to the 1st sympathetic trunk. Histological examination of the surgical specimen showed that it was a paraganglioma, and neurosecretary granules were found on Grimelius staining microscopic examination. In the Japanese literature, only 13 cases of intrathoracic paraganglioma or pheochromocytoma is reported. The literature was reviewed.

Refilling the lens with a inflatable endocapsular balloon: surgical procedure in animal eyes.

In this report we describe the surgical details involved in refilling the lenses of 13 rabbit and 3 primate eyes using an inflatable endocapsular balloon to restore accommodation. The procedure involves endocapsular phacoemulsification through a small "buttonhole" or "dumbbell" anterior capsulotomy or minicircular capsulotomy and the simultaneous preservation of capsular integrity, including the zonules and ciliary muscles. An inflatable balloon made of thin silicone membrane is then inserted into the empty capsular bag. A liquid silicone polymer is injected into the balloon through a delivery tube, and the empty capsular bag is refilled by the inflated balloon. The procedure was found to be reproducible, and an accommodation of 6 D was confirmed in one primate eye. Capsular opacification occurred, but the proliferation and migration of residual lens epithelial cells could be hindered by abundant refilling. This lens-refilling technique may provide restoration of accommodation in future cataract surgery.

Lysozyme loading and release from hydrogels carrying pendant phosphate groups.

To develop a polymeric matrix for efficiently loading cationic biomolecules, polyelectrolyte hydrogels carrying pendant phosphate groups were synthesized by copolymerizing 2-methacryloyloxyethyl dihydrogen phosphate with N-isopropylacrylamide and N, N1-methylene-bis-acrylamide. The phosphate-carrying monomer yielded anionic hydrogels, which formed ionic complexes with the cationic protein, lysozyme. It was shown that the amount of complexed lysozyme reached 2.1 g g-1 dry gel, corresponding to 1.3 x 10(-3) mol phosphate group per gram lysozyme, when 40 mol% of phosphate-carrying monomer was incorporated in a hydrogel. When the hydrogel complexed with lysozyme was placed in deionized water and various KCl solutions, of varying concentrations of up to 0.5 M KCl, no lysozyme was released in deionized water, while increasing amounts of lysozyme were released as the KCl concentration increased. This confirmed that lysozyme was loaded in the hydrogel through electrostatic interactions. It was further found that the complexed lysozyme retained its enzymatic activity after being released from the hydrogel. These results suggest the use of this system for the controlled release of cationic protein drugs.

Founder's Award, Society for Biomaterials. Sixth World Biomaterials Congress 2000, Kamuela, HI,May 15-20, 2000. Really smart bioconjugates of smart polymers and receptor proteins.

Over the past 18 years we have been deeply involved with the synthesis and applications of stimuli-responsive polymer systems, especially polymer-biomolecule conjugates. This article summarizes our work with one of these conjugate systems, specifically polymer-protein conjugates. We include conjugates prepared by random polymer conjugation to lysine amino groups, and also those prepared by site-specific conjugation of the polymer to specific amino acid sites that are genetically engineered into the known amino acid sequence of the protein. We describe the preparation and properties of thermally sensitive random conjugates to enzymes and several affinity recognition proteins. We have also prepared site-specific conjugates to streptavidin with temperature-sensitive polymers, pH-sensitive polymers, and light-sensitive polymers. The preparation of these conjugates and their many fascinating applications are reviewed in this article.