Ultrasound-guided injection of the cranial tibial artery for stem cell administration in horses.

BACKGROUND: A technique for intra-arterial injection of mesenchymal stem cells (MSC) has been established for front limbs with the use of the median artery. This approach has been proposed for treatment of soft tissue injuries of the equine distal limb. A technique has not been validated yet for hindlimb injection. OBJECTIVES: To assess the feasibility of injection of the cranial tibial artery in horses, and to evaluate the distribution and persistence of MSC after injection. STUDY DESIGN: In vivo experiment. METHODS: In a first phase, the cranial tibial arteries of both hindlimbs of three research horses were catheterised with ultrasound guidance under general anaesthesia and injected with iodinated contrast. In the second phase, iodinated contrast was injected in three standing sedated horses with ultrasound guidance. In the final phase, 99m Technetium-HMPAO labelled allogenic bone marrow derived equine MSC were injected under standing sedation with the same technique in three other horses. Scintigraphy was used to assess MSC distribution and persistence for 24 h. Ultrasound was performed 24 h after injection to assess vessel impairment. RESULTS: Arterial injection was achieved in all 18 limbs without any significant complications. Mild partial periarterial injection was observed in four limbs. Scintigraphic images demonstrated diffuse MSC distribution from the tarsal area to the foot. Persistence decreased over time but signal was still present at 24 h. MAIN LIMITATIONS: Limited retention of the radiolabel in the MSC. CONCLUSIONS: Ultrasound-guided injection of the cranial tibial artery can be performed both under general anaesthesia and standing sedation in horses. This technique could be used for MSC treatment of equine proximal suspensory desmopathy or other injuries in the distal hindlimb.

Autologous point-of-care cellular therapies variably induce equine mesenchymal stem cell migration, proliferation and cytokine expression.

REASONS FOR PERFORMING STUDY: Autologous cellular therapy products including adipose-derived stromal vascular fraction (SVF), bone marrow mononuclear cells (BMMNs), cord blood mononuclear cells (CBMNs) and platelet rich plasma are options for treatment of acute orthopaedic lesions while mesenchymal stem cells (MSCs) are culture expanded. These products may contribute to healing by secreting matrix proteins or growth factors, but they may also act on endogenous MSCs to facilitate healing. OBJECTIVES: To determine the effects of cell therapy products on MSCs function in vitro. The hypothesis was that cell therapy products promote MSCs functions including proliferation, migration and mediator release. METHODS: Fat, bone marrow (BM), cord blood and platelets were obtained from 6 Quarter Horses. The BM-MSCs and their autologous cell therapy products were co-incubated in transwells. Mesenchymal stem cells proliferation, migration, gene expression and cytokine concentrations were determined. RESULTS: All cell therapy products increased MSCs proliferation, but SVF induced significantly more proliferation than any other product. Also SVF elicited more MSCs chemotaxis and, along with BMMNs, significantly more MSCs chemoinvasion. Cord blood mononuclear cells stimulated MSCs to produce high concentrations of interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and prostaglandin E(2) (PGE(2)). Stromal vascular fraction and platelet lysate did not stimulate MSCs but SVF and platelet lysate themselves contained high concentrations of PGE(2) and IL-6 (SVF) and TGF-ß1 (platelet lysate). CONCLUSIONS: Autologous cell products variably stimulate MSCs functions with 2 primary patterns apparent. Products either contained preformed mediators that may have intrinsic healing function, or products stimulated MSCs to secrete mediators. POTENTIAL RELEVANCE: The specific clinical indications for these products may differ to include administration as a sole treatment modality prior to MSCs injection for intrinsic cell and cytokine activity (i.e. SVF) or administration concurrently with MSCs to activate MSCs for treatment of chronic lesions (i.e. CBMNs).

Inhibition of tetanus toxin fragment C binding to ganglioside G(T1b) by monoclonal antibodies recognizing different epitopes.

Anti-tetanus toxoid monoclonal antibodies would be useful in exploring the relationship of tetanus toxin structure to its function. Tetanus toxin fragment C has been shown to be responsible for binding to neurons via gangliosides. Eleven new and two previously derived monoclonal antibodies specific for tetanus toxin fragment C were shown to recognize five different fragment C epitopes, two of which were overlapping. Three of these epitopes participate in the binding to ganglioside G(T1b). One epitope was defined by a monoclonal antibody that did not inhibit the interaction between fragment C and ganglioside. This antibody however, was blocked from binding to fragment C by antibodies that were able to inhibit the fragment C-ganglioside interaction.

Plasmatocyte spreading peptide does not induce Microplitis demolitor polydnavirus-infected plasmatocytes to spread on foreign surfaces.

Capsule formation by the moth Pseudopulsia includens requires that plasmatocytes change from being nonadhesive cells in circulation to strongly adhesive cells capable of attaching to the foreign target and one another. This change in adhesive state is induced by Plasmatocyte Spreading Peptide (PSP1); a 23 amino acid peptide isolated from P. includens plasma. Plasmatocytes from hosts parasitized by Microplitis demolitor remain in a nonadhesive state after infection by Microplitis demolitor polydnavirus (MdPDV). This alteration in plasmatocyte function prevents P. includens from encapsulating the developing parasitoid. In the current study, we examined whether MdPDV infection eliminates PSP1-responsive plasmatocytes from circulation or disrupts the ability of PSP1 to induce adhesion and spreading of plasmatocytes to foreign surfaces. In vivo experiments revealed that infection of P. includens by MdPDV induced an increase in the total number of hemocytes in circulation but reduced the proportion of hemocytes in circulation that were plasmatocytes. However, plasmatocytes normally capable of responding to PSP1 were not eliminated from circulation. Both in vivo and in vitro experiments indicated that plasmatocytes inoculated with MdPDV lost the capacity to respond to PSP1 4-6 h post-infection. Infection of P. includens with MdPDV reduced expression levels of prepro-PSP1 mRNA in hemocytes but did not appear to alter expression levels in fat body.

Primary malignant melanoma of the uterine cervix: case report with world literature review.

A 63-year-old patient with a malignant melanoma of the uterine cervix is described. Subtle epitheliotropism of the neoplastic cells within the endocervical columnar epithelium suggested melanoma in situ and the possibility of a primary uterine cervical melanoma, despite a negative anti-S-100 protein immunohistochemical stain. An exhaustive clinical workup, and ultimately, complete autopsy failed to reveal any other primary tumor site, and the diagnosis of melanoma was confirmed by histology and immunohistochemistry on the hysterectomy specimen. A world literature review revealed 54 previously reported cases of uterine cervical melanoma of which 43 had been reported as primary uterine cervical melanoma. A true intraepithelial melanocytic component was found in only 14 of those cases, however, and none of those reports illustrated this with the clarity with which it was seen in the endocervical glandular and surface columnar epithelium of the present case. Primary uterine cervical melanoma is usually discovered at an advanced stage and is no longer amenable to curative therapy. Even when this tumor is discovered early, however, the diagnosis may be unnecessarily delayed if the often subtle interaction of the neoplastic cells with the benign cervical squamous or glandular epithelium is not appreciated, or if the possibility of malignant melanoma is not entertained based on other histologic or immunohistologic characteristics of the tumor cells.

Limited magnetic resonance imaging in the diagnosis of occult hip fractures.

The majority of fractures of the hip are readily diagnosed on the basis of the clinical findings and plain radiographs. When initial X-rays are negative or equivocal and a high clinical suspicion exists for an occult hip fracture, additional diagnostic studies need to be performed. Use of limited magnetic resonance imaging in the diagnosis of occult hip fracture upon initial presentation to the emergency department is reported.

Optimism versus pessimism predicts the quality of women's adjustment to early stage breast cancer.

BACKGROUND: Recent studies indicate that breast cancer patients do not usually experience the devastating psychological consequences once viewed as inevitable. However, some adjust to the disease more poorly than others. This study examined the personality trait of optimism versus pessimism as a predictor of adjustment over the first year, postsurgery. METHODS: Seventy women with early stage breast cancer reported on their general optimism-pessimism at diagnosis. One day before surgery, and at 3-month, 6-month, and 12-month follow-ups, they reported their subjective well-being (mood scales and a measure of satisfaction with life). At follow-ups, they also rated their sex lives, indicated how much physical discomfort was interfering with their daily activities, and reported on thought intrusion. RESULTS: Pessimism displayed poorer adjustment at each time point by all measures except interference from pain. Even controlling for previous well-being, pessimism predicted poorer subsequent well-being, suggesting that pessimism represents a vulnerability to a negative change in adjustment. In contrast, effects of pessimism on quality of sex life and thought intrusion were not incremental over time. Additional analyses indicated that effects of the optimism-pessimism measure were captured relatively well by a single item from the scale. CONCLUSIONS: A sense of pessimism about one's life enhances a woman's risk for adverse psychological reactions to the diagnosis of, and treatment for, breast cancer. This finding suggests the potential desirability of assessing this quality informally in patients, to serve as a warning sign regarding the patient's well-being during the period surrounding and following surgery.

Radioimmunodetection of colorectal carcinoma using technetium-99m-labeled Fab' fragments of the IMMU-4 anti-carcinoembryonic antigen monoclonal antibody.

BACKGROUND: Radioimmunodetection of cancer using monoclonal antibody fragments offers certain potential advantages over that with whole monoclonal antibodies, including the ability to image early (i.e., to provide images at an early time after injection of the radioantibody) while minimizing the incidence of human anti-mouse antibody response. This paper reports a prospective trial comparing radioimmunodetection with IMMU-4 (a murine anti-CEA monoclonal antibody) 99mTc-labeled Fab' fragments to conventional imaging in 35 colorectal cancer patients. METHODS: All patients were investigated by conventional diagnostic methods (CDM) within 4 weeks of radioimmunodetection. Surgical corroboration of findings was obtained in 26 patients (15 with evidence of disease on CDM [CDM+] and 11 with abnormal serum CEA [CDM-] as the only evidence for recurrence). After 1 mg IMMU-4 99mTc-Fab' was injected (19.3 mCi on average), patients underwent planar/SPECT radioimmunodetection 2-5 hours later and planar radioimmunodetection 18-24 hours later. Three patients underwent a second radioimmunodetection study 16, 20 and 23 months after the first. RESULTS: Radioimmunodetection was superior to CDM, accurately predicting disease distribution in six nonsurgical and ten CDM+ surgical patients, and was complementary to computed tomography in two nonsurgical and two CDM+ surgical patients. Radioimmunodetection would have directed or changed management decisions in 6 of the 15 (40%) CDM+ surgical patients. Radioimmunodetection correctly identified all recurrent tumor in 8 of 11 CDM- surgical patients and was negative in one patient with cirrhosis and no recurrence, representing a potential clinical benefit of 82%. Analyzed on a regional basis, radioimmunodetection was found to be superior to CDM in extrahepatic abdomen and pelvis imaging and was complementary to (although not as accurate as) CDM in the liver. Human anti-mouse antibody did not develop in any of the patients, including three who were injected twice. CONCLUSIONS: IMMU-4 99mTc-Fab' radioimmunodetection shows promise as a clinically useful diagnostic tool in patients with colorectal cancer, detecting disease often missed by conventional imaging. IMMU-4 99mTc-Fab' may prove useful for serial radioimmunodetection studies, because human anti-mouse antibody response does not appear to be a problem with this radioimmunoconjugate. It also has the advantage of permitting same-day imaging.

Electro-optic high-resolution Fabry-Perot spectrometer.

A single-crystal lithium niobate dtalon suitable for high-spectral-resolution studies has been operated successfully. This étalon with a 5-cm clear diameter and a gap equivalent to 2 cm in air has been found to have very linear response in wave number as a function of voltage. The combined advantages of adjustment-free operation, linearity in operation, and high luminosity in a small size (as a result of the µ(2) gain in the instrumental throughput caused by the large index of refraction of the lithium niobate substrate) make for a rugged instrument that is ideal for long-term unattended field operation.

How coping mediates the effect of optimism on distress: a study of women with early stage breast cancer.

At diagnosis, 59 breast cancer patients reported on their overall optimism about life; 1 day presurgery, 10 days postsurgery, and at 3-, 6-, and 12-month follow-ups, they reported their recent coping responses and distress levels. Optimism related inversely to distress at each point, even controlling for prior distress. Acceptance, positive reframing, and use of religion were the most common coping reactions; denial and behavioral disengagement were the least common reactions. Acceptance and the use of humor prospectively predicted lower distress; denial and disengagement predicted more distress. Path analyses suggested that several coping reactions played mediating roles in the effect of optimism on distress. Discussion centers on the role of various coping reactions in the process of adjustment, the mechanisms by which dispositional optimism versus pessimism appears to operate, third variable issues, and applied implications.

A comparison of the actions of agonists and antagonists at non-NMDA receptors of C fibres and motoneurones of the immature rat spinal cord in vitro.

1. The shift in d.c. potential in dorsal roots (EC50 8.0 microM +/- 0.9 s.e. mean, n = 5) or depression of the C elevation of the compound action potential (EC50 3.0 microM +/- 0.3, n = 7) have been used to measure the depolarizing action of kainate on dorsal root C fibres of immature (3 to 5 day old) rats. Depolarization of motoneurones was measured from the shift in d.c. potential in ventral roots. 2. 6-Cyano-7-nitroquinoxaline,2-3,dione (CNQX) (pA2 5.78 +/- 0.06, n = 8) and 6-nitro-7-suplhamobenzo(f)quinoxaline-2,3-dione (NBQX) (pA2 5.75 +/- 0.04, n = 7) had similar potencies as antagonists of kainate at dorsal root fibres. The potency of NBQX as a kainate antagonist was similar also at motoneurones (pA2 5.72 +/- 0.07, n = 3). At motoneurones, NBQX was less potent as an antagonist of domoate (pA2 5.29 +/- 0.05) and more potent as an antagonist of S-alpha-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (pA2 6.80 +/- 0.09) than as an antagonist of kainate. 3. Application of L-glutamate, quisqualate and RS-AMPA to dorsal roots produced only short lasting depolarizations but kainate concentration-effect plots were shifted to the right in the presence of these three agonists (pA2 5.08 +/- 0.08, (n = 3), 5.59 +/- 0.04, (n = 4) and 4.46 +/- 0.04 (n = 4) respectively). Slopes of dose-ratio against concentration were significantly less than one for the latter antagonism. 4. The amplitude of depolarizations induced by L-glutamate, AMPA and quisqualate were increased up to ten fold and those induced by kainate up to two fold following treatment of dorsal roots with concanavalin A. The duration of the responses was increased also by the latter treatment. Folowing 85 s applications of glutamate, quisqualate, AMPA and kainate the mean respective times (s +/- s.e.mean (n))taken for responses to decay to half the peak amplitude were increased from 63 +/- 7 (10), 86 +/- 17 (4),95 +/- 19 (4) and 135 +/- 3 (12) to 202 +/- 49 (10), 147 +/- 7 (4), 160 +/- 13 (6) and 163 +/- 10 (10). Under similar conditions the mean decay time of y-aminobutyric acid-induced responses was 145 +/- 7 (10). This was not significantly altered by concanavalin A treatment.5. Application to dorsal roots of L-aspartate at concentrations up to 5 mm (with or without concanavalin A treatment), the selective metabotropic agonist 1S,3R-trans-1-aminocyclopentane-1,3-dicarboxylate (1 mM,) and D-serine (20 pM) in the presence or absence of N-methyl-D-aspartate (NMDA,500 pM) neither depolarized the preparations nor shifted the kainate concentration-effect plot.6. It is concluded that primary afferent C fibres possess only one type of non-NMDA receptor which is activated strongly by domoate or kainate but only weakly by AMPA. This receptor is readily desensitized by glutamate, quisqualate or AMPA and it is less readily desensitized by kainate.

Axillary node dissection for early breast cancer: some is good, but all is better.

Optimal management of the axillary lymphatics in breast cancer patients remains a contentious subject. Axillary recurrence, while infrequent, may have very significant clinical consequences in the affected patient. Axillary sampling, partial and total axillary lymphadenectomy, radiotherapy, and surgery plus radiotherapy are discussed with attention to efficacy in prevention of axillary recurrence, accuracy of nodal staging, and morbidity. The incidence of axillary recurrence decreases and accuracy of staging increases with the number of lymph nodes resected. There is little difference in incidence of morbidity between partial and total axillary lymphadenectomy. Radiotherapy is not as effective as lymphadenectomy for regional disease control and, when administered following a surgical staging procedure, increases the risk of lymphedema of the ipsilateral upper extremity and, in patients undergoing breast-conserving surgery, the ipsilateral breast. We believe that total axillary lymphadenectomy provides optimal regional disease control and axillary staging with morbidity comparable to that of partial lymphadenectomy.

Effects of mastectomy versus lumpectomy on emotional adjustment to breast cancer: a prospective study of the first year postsurgery.

PURPOSE: Procedure (mastectomy v lumpectomy) and choice of procedure were examined as predictors of adjustment to breast cancer in a prospective study of the experiences of the first year after surgery. PATIENTS AND METHODS: Breast cancer patients were interviewed the day before surgery, 10 days after surgery, and at the 3-month, 6-month, and 12-month follow-ups. Patients included 24 women who received mastectomy on strong recommendation, 24 who chose mastectomy for other reasons, and 15 who chose lumpectomy. Subjective well-being was assessed in terms of mood disturbance, perceived quality of life, life satisfaction, marital satisfaction, perceptions of social support, and self-rated adjustment. RESULTS: Surgical groups differed in well-being in only one respect: lumpectomy patients reported a higher-quality sex life at 6 and 12 months postsurgery than mastectomy patients. Choice of surgical procedure predicted higher levels of life satisfaction at 3 months. CONCLUSION: The lack of difference between surgical groups in areas other than sexual adjustment replicates previous findings, but extends them by (1) using a fully prospective design, (2) providing data on the period surrounding the surgery (as well as later periods), and (3) examining a broader range of indices of well-being than usual.

Total axillary lymphadenectomy in the management of breast cancer.

The optimal extent of axillary dissection in patients with breast cancer remains unclear. We report 278 total axillary lymphadenectomies (levels I, II, and III and Rotter's [interpectoral] nodes) that were performed in 264 closely followed up private patients. There have been no axillary recurrences to date (mean follow-up, 50 months). If only level I and II nodes had been removed, the false-negative staging error would have been only 2.6%. However, 29 (31.5%) of 92 pathological node-positive axillae contained apical and/or Rotter's metastases. The incidence of complications was comparable with that reported for partial lymphadenectomy. Arm lymphedema developed in 6% of nonirradiated patients; postoperative radiotherapy and gross nodal disease were significant risk factors for lymphedema. Total axillary lymphadenectomy largely prevents axillary, recurrence, eliminates the small staging error inherent in partial lymphadenectomy, and has acceptable morbidity, provided radiotherapy to the regional nodal areas is avoided.

Nonoperative techniques for tissue diagnosis in the management of thyroid nodules and goiters.

As only 10% of thyroid nodules are malignant, the surgical oncologist is faced with the challenge of selecting for thyroidectomy only those patients likely to benefit therapeutically from surgery. Demonstration of nonfunction on scintigraphic thyroid scan increases the yield of cancer only by 15% to 20%. Aspiration cytology and needle biopsy are potent aids in selecting patients for thyroidectomy. In 1,504 patients for whom a benign or malignant cytological diagnosis was made prior to thyroidectomy, the sensitivity of this technique was 92.0%, specificity was 97.3%, and overall diagnostic accuracy 95.7%. Morbidity is minimal. The reliability of these techniques is dependent on proficient specimen procurement and the cytopathologist's expertise and experience. Differentiation of benign from malignant follicular and lymphocytic lesions is not possible with conventional cytology preparations; 28% of such "indeterminant" lesions prove to be cancer at thyroidectomy. Aspiration cytology is a simple, reliable technique for selection of patients with thyroid nodules for surgery.

Matched tandem etalon camera-MATEC-and its application to auroral observations.

The matched tandem etalon camera (MATEC) offers the high resolution of the Fabry-Perot interferometer combined with the separate advantages of a flexible image format and photon array detection. In certain applications involving complex or continuum spectra, the simultaneous detection of data over a wide spectral and spatial range can result in a large increase in effective data-taking speed over that obtainable by scanning the same range. In this new type of tandem etalon device, an intercalated field lens, whose spacing and power are both critical, allows a dielectric interference filter to isolate the same order of an airspaced Fabry-Perot at all angles of transmission. In the MATEC the field of view is imaged on a photon array detector to provide simultaneous detection of all throughput wavelengths. In a system applied to auroral measurements known as the meridian etalon camera (MEC), the MATEC views a semiconical sky mirror to provide a simultaneous dimension of spatial resolution in the N-S meridian comined with the dimension of spectral resolution. Stellar features and cloud and ground reflections are much more easily identified in the MEC format than by any scanning photometer.

Measurements and parameterization of the bidirectional reflectance factor of BaSO(4) paint.

Comprehensive measurements of the bidirectional reflectance factor of BaSO(4) paint vs both viewing and illumination angles are presented as contour plots. Contours resulting from several surfacing techniques are compared to demonstrate that a machined surface on a thick BaSO(4) deposit gives the most reproducible diffuse reflectivity. It is also shown that a spray deposit of BaSO(4) gives a much less diffuse reflectivity. We also show that the contours of bidirectional reflectance of either machined BaSO4 or smoked MgO may be described by a three-parameter fit, which automatically obeys the Helmholtz reciprocity theorem and is simply related to the efficiency of total reflectance.