A SLAP lesion associated with calcific tendinitis of the long head of the biceps brachii at its origin

Calcific tendinitis is a common condition with characteristic clinical and radiological findings. Although we do not know which condition initiated the pathologic cascade, we present a rare case of calcific tendinitis of the long head of the biceps brachii at its origin, associated with a SLAP lesion. The calcium deposit was removed and the SLAP lesion was repaired with a suture anchor arthroscopically.     

Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia.

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is capable of inhibiting nitric oxide synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. The potential role of inflammation in the metabolism of ADMA has been elucidated in an in vitro model using tumour necrosis factor-alpha, resulting in a decreased activity of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH). The kidney probably plays a crucial role in the metabolism of ADMA by both urinary excretion and degradation by DDAH. We aimed to further elucidate the role of the kidney in a rat model under basal conditions and during endotoxaemia. METHODS: Twenty-five male Wistar rats weighing 275-300 g were used for this study. The combination of arteriovenous concentration differences and kidney blood flow allowed calculation of net organ fluxes. Blood flow was measured using radiolabelled microspheres according to the reference sample method. Concentrations of ADMA, SDMA and arginine were measured by high-performance liquid chromatography. RESULTS: The kidney showed net uptake of both ADMA and SDMA and fractional extraction rates were 35% and 31%, respectively. Endotoxaemia resulted in a lower systemic ADMA concentration (P = 0.01), which was not explained by an increased net renal uptake. Systemic SDMA concentrations increased during endotoxaemia (P = 0.007), which was accompanied by increased creatinine concentrations. CONCLUSIONS: The rat kidney plays a crucial role in the regulation of concentrations of dimethylarginines, as both ADMA and SDMA were eliminated from the systemic circulation in substantial amounts. Furthermore, evidence for the role of endotoxaemia in the metabolism of dimethylarginines was obtained as plasma levels of ADMA were significantly lower in endotoxaemic rats.     

Dendritic Cells Coinjected with Tumor Cells Treated with an Anticancer Drug to Induce Tumor Rejection

Purpose: We examined whether bone marrow-derived dendritic cells (DCs) could induce antitumor immunity when a chemotherapeutic drug was added. Methods: CT26 (a murine colon cancer cell line syngeneic with BALB/c) and CT26-bearing mice were treated with mitomycin C (MMC) intraperitoneally (i.p.). Next, mice immunized with a coinjection of DCs and MMC-treated CT26 (i.p.) were given an intradermal inoculation of CT26. Finally, CT26-bearing mice were treated with MMC (i.p.) with or without DCs, given peritumorally. Results: Although the inoculated tumor was not rejected in the control mice, CT26 was rejected in 50% of the mice injected with MMC alone. Apoptosis was observed in the MMC-treated CT26 cells in vitro and in vivo. Immunization with DCs and apoptotic CT26 cells, but not with apoptotic CT26 alone, gave protection against tumor challenge in 7 of 13 mice. A significantly higher level of cytotoxic T-cell activity and interferon-γ production was seen in the protected mice. When MMC (i.p.) treatment was followed by peritumoral DC injection in the CT26-bearing mice, remarkable therapeutic effects were observed. Conclusion: DCs can collaborate with chemotherapy-induced apoptotic tumor cells and elicit improved antitumor immunity, probably through the acquisition of tumor-associated antigens from apoptotic tumor cells. Received: January 7, 2002 / Accepted: September 3, 2002 Acknowledgments. We thank Dr. Kazuo Kinoshita for his useful advice on using flow cytometry. This research was partly supported by the Ministry of Education, Culture, Sports, Science and Technology (No. 11671160). Reprint requests to: S. Yamasaki     

A systemically administered neurotensin agonist blocks disruption of prepulse inhibition produced by a serotonin-2A agonist.

Prepulse inhibition (PPI) of the startle reflex can be disrupted by drugs that act as agonists at the serotonin (5-HT) 2A receptor, such as DOI, and this effect is blocked by drugs that inhibit 5-HT2A transmission. We tested the effects of systemic administration of PD149163, a neurotensin agonist, on DOI-induced disruption of PPI in Sprague-Dawley rats. PD149163 completely and dose dependently blocked the PPI deficits produced by DOI. These findings suggest that, in addition to their established ability to inhibit dopamine transmission, neurotensin agonists may also inhibit 5-HT2A transmission, a pharmacological feature associated with atypical antipsychotic drugs.     

Congenital absence of the inferior rectus muscle--diagnosis and management.

BACKGROUND: Congenital absence of the inferior rectus muscle is a rare cause of apparent inferior rectus palsy especially in the absence of associated cranial facial anomalies. METHODS: We report three cases of isolated congenital absence of the inferior rectus muscle and its successful surgical management. RESULTS: Failure of the normal embryologic development of the mesodermal complex around the eye can lead to agenesis of the extraocular muscles. In apparent palsies of the inferior rectus muscle and no definite cause, a high index of suspicion and orbital imaging can confirm the diagnosis of congenitally absent inferior rectus preoperatively. Surgical correction may involve inferior transposition of the horizontal rectus muscles. CONCLUSIONS: Although rare, congenital absence of the inferior rectus muscle is a possible cause of apparent inferior rectus muscle palsy particularly in the absence of another identifiable cause. Strabismus surgery in conjunction with intramuscular botulinum toxin injection can offer significant improvement in function and cosmesis of these patients.     

Dural Tissue Trauma and Cerebrospinal Fluid Leak after Epidural Needle Puncture: Effect of Needle Design, Angle, and Bevel Orientation

Background: The effects of epidural needle design, angle, and bevel orientation on cerebrospinal fluid leak after puncture have not been reported. The impact of these factors on leak rate was examined using a dural sac model. Dural trauma was examined using scanning electron microscopy.

Methods: Human cadaveric dura, mounted on a cylindrical model, was punctured with epidural needles using a micromanipulator. Tissue was punctured at 15 cm H2O (left lateral decubitus) system pressure, and leak was measured at 25 cm H2O (semisitting) pressure. Leak rates and trauma were compared for the following: (1) six different epidural needles at 90[degrees], bevel parallel to the dural long axis; (2) 18-gauge Tuohy and 18-gauge Special Sprotte(R) epidural needles, 30[degrees]versus 90[degrees]; (3) 18-gauge Tuohy, bevel perpendicular versus parallel to the dural long axis.

Results: With the 90[degrees] puncture, bevel parallel, the greatest leak occurred with a 17-gauge Hustead (516 +/- 319 ml/15 min), and the smallest leak occurred with a 20-gauge Tuohy (100 +/- 112 ml/15 min; P = 0.0018). A 20-gauge Tuohy puncture led to statistically significant reductions in leak (P value range, 0.0001-0.0024) compared with all needles except the Special Sprotte(R). With the 30[degrees]versus 90[degrees] angle, 30[degrees] punctures with an 18-gauge Tuohy produced nonstatistically significant leak reductions compared with the 18-gauge Tuohy at 90[degrees]. The puncture angle made no difference for the Special Sprotte(R). Nonsignificant reductions were found for the Special Sprotte(R) compared with the Tuohy. With the 18-gauge Tuohy bevel orientation, perpendicular orientation produced nonstatistically significant reductions in leak compared with parallel orientation.     

Optical Pretargeting of Tumor with Fluorescent MORF Oligomers

Objective Pretargeting with radioactivity has significantly improved tumor to normal tissue radioactivity ratios over conventional antibody imaging in both animal studies and clinical trials. This laboratory is investigating DNA analogues such as phosphorodiamidate morpholinos (MORFs) for pretargeting using technetium-99m (^99mTc) for detection. However, the unique properties of fluorescence activation and quenching combined with oligomers with their unique properties of hybridization may be particularly useful when used together for pretargeting with optical detection. The use of linear fluorophore-conjugated oligomer duplexes have been little used in animals, and to our knowledge, have not previously been considered for pretargeting applications. Methods A MORF/cDNA pair was selected such that when hybridized, the fluorescence of the Cy5.5-conjugated 25 mer MORF (Cy5.5–MORF25) is inhibited with a BHQ3-conjugated 18 mer complementary DNA (BHQ3–cDNA18). The short BHQ3–cDNA18 was selected to dissociate in the presence of a long cMORF25 in the pretargeted tumor, thus releasing the inhibitor from the Cy5.5 emitter. In this manner, the Cy5.5 fluorescence will be inhibited everywhere but in the target. The dissociation was first examined in vitro by adding the duplex to the cMORF25 both in solution and immobilized on polystyrene microspheres and by surface plasmon resonance (SPR). Thereafter, biotinylated cMORF25 immobilized on streptavidin polystyrene microspheres were administered intramuscularly in one thigh of hairless SKH-1 mice as target while an identical weight of the identical microspheres but without the cMORF25 was administered in the contralateral thigh as control. The animals then received IV the Cy5.5–MORF25/BHQ3–cDNA18 duplex or equal molar dosage of single-chain Cy5.5–MORF25 and were imaged. Results The SPR studies showed that the immobilized cDNA18 rapidly captured the flowing MORF25 to provide a duplex with a slow dissociation rate constant. Furthermore, when cMORF25 was next allowed to flow over the now immobilized duplex, the cDNA18 was unable to prevent dissociation of the heteroduplex and the formation and release of the cMORF25-MORF25 homoduplex. Images of animals obtained soon after receiving the Cy5.5–MORF25 singlet showed intense whole body fluorescence obscuring the target thigh. However, only 5 minutes after receiving the Cy5.5–MORF25/BHQ3–cDNA18 duplex, the target thigh was clearly visible along with only the kidneys. Conclusions This first study of optical pretargeting provides a proof of concept that oligomer pretargeting found to be useful with radioactivity detection is applicable with fluorescent detection as well. In addition, our results demonstrate that by using linear oligomers for optical pretargeting, chain lengths (and base sequences) may be manipulated to provide duplexes with stabilities and fluorescence inhibition optimized for pretargeting and other in vivo applications of optical imaging.