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Fluorescence microlymphography.

Microneedles, 0.2 mm o.d., were connected to a microsyringe and mounted on a micromanipulator. Under microscopic control, 0.01 ml of a 25% solution of FITC-labeled dextran-40 or dextran-150 were injected into the subepidermis at the big toe near the nailfold or in the medial ankle region. Fluorescence intravital microscopy revealed a network of lymphatic microvessels. The comparison with recent anatomic studies reveals that the reticular network visualized by FITC-dextran corresponds to the network in the stratum papillare. In 20 healthy subjects lymphatic capillaries were detected in a restricted area on the lateral aspect of the big toe. In 10 patients with primary lymphedema, the dye expanded to almost the entire dorsal skin surface of the big toe. In two cases, enlarged and tortuous microvessels of pathologic shape were observed. Fluorescence microlymphography is a simple and nearly atraumatic approach for depicting the intravital anatomy of human skin lymphatic capillaries.

Adult↗

Intraocular lymphoma: update on diagnosis and management.

BACKGROUND: Primary intraocular lymphoma (PIOL) is a subset of primary central nervous system lymphoma (PCNSL) in which lymphoma cells initially invade the retina, vitreous, or optic nerve head, with or without concomitant CNS involvement. The incidence of this previously rare condition has increased dramatically. Given its nonspecific presentation and aggressive course, PIOL provides a diagnostic and therapeutic challenge. METHODS: We review the current strategies for diagnosis and treatment of PIOL and present our own experience with PIOL. RESULTS: Recent developments in the diagnosis of PIOL include immunohistochemistry, flow cytometry, cytokine evaluation, and molecular analysis. However, definitive diagnosis still requires harvesting of tissue for histopathology. Optimal treatment for PIOL remains unclear. Initial therapeutic regimens should include methotrexate-based chemotherapy and radiotherapy to the brain and eye. In addition, promising results have been seen with intravitreal methotrexate and autologous stem cell transplantation for recurrent and refractory disease. CONCLUSIONS: Efforts to further determine the immunophenotype and molecular characteristics of PIOL will continue to assist in the diagnosis of PIOL. Future studies are required to determine the role of radiotherapy and optimal local and systemic chemotherapeutic regimens.

Antimetabolites, Antineoplastic↗

Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen.

Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system capable of initiating primary immune responses to neoantigens. Here we characterize the primary CD4 T-cell immune response to protein keyhole limpet hemocyanin (KLH) in 5 metastatic melanoma patients undergoing a tumor peptide-based dendritic cell vaccination trial. Monocyte-derived dendritic cells displaying a semimature phenotype, as defined by surface markers, were loaded ex vivo with antigen and injected intranodally at weekly intervals for 4 weeks. All patients developed a strong and long-lasting delayed-type hypersensitivity reactivity to KLH, which correlated with the induction of KLH-dependent proliferation of CD4 T cells in vitro. Secondary in vitro stimulation with KLH showed significant increase in interferon-gamma and interleukin-2 (IL-2) but not IL-4, IL-5, nor IL-10 secretion by bulk T cells. On the single-cell level, most TH1 cells among in vitro-generated KLH-specific T-cell lines confirmed the preferential induction of a KLH-specific type 1 T helper immune response. Furthermore, the induction of KLH-specific antibodies of the IgG2 subtype may reflect the induction of a type 1 cytokine profile in vivo after vaccination. Our results indicate that intranodal vaccination with semimature DCs can prime strong, long-lasting CD4 T-cell responses with a TH1-type cytokine profile in cancer patients.

Antibody Formation↗

Clinical radionuclide perfusion lymphangiography.

In an initial pilot study technetium-99m-labelled human serum albumin was perfused directly into bipedal lymphatic cannulae prior to a standard lymphangiogram, in order to assess rapidly normal and abnormal lymph flow patterns in the lower extremity, pelvic and para-aortic lymph chains. A continuing study of these patients has lent further support to the hypothesis that the radionuclide perfusion study, when negative, may prove more accurate in some patients than the standard lymphangiogram in predicting the clinical course and/or the results of histopathological lymph node examination. The radionuclide technique also seems to meet, in this preliminary evaluation, the requirements for a pre-lymphangiogram screening study, particularly for use in high-risk patients.

Humans↗

Laryngeal lymphoscintigraphy.

A method of studying lymphatic drainage of the larynx was undertaken using radioactive colloids. Sites of injection were the true and false cords, aryepiglottic folds, anterior and posterior commissure, epiglottis and arytenoid. The patient was then scanned with the gamma camera 3 to 5 hours and again 24 hours post injection. Thirty-six patients were injected and results were recorded as to previous X-ray therapy, nodal activity post scanning, ipsilateral or contralateral and distant spread, and the type of radioactive particle--99mTc labeled sulfur colloid, 99mTc microalbumin (200-800 nm diameter), and 99mTc minimicroalbumin (less than 50 nm diameter). The three radiopharmaceuticals gave similar results. Previous X-ray therapy did not alter lymphatic drainage. Of 36 patients, 23 showed nodal activity on scintiscanning: none showed any axillary nor mediastinal activity.

Carcinoma, Squamous Cell↗

Perilymphatic injections of recombinant interleukin-2 (rIL-2) partially correct the immunologic defects in patients with advanced head and neck squamous cell carcinoma.

Patients with advanced head and neck squamous cell carcinoma (HNSCC) are severely immunocompromised. In virtually all such patients who have been studied, reduced numbers of circulating CD3+ T-cell-receptor (TCR)alpha/beta+ T lymphocytes, a reduction of natural killer (NK) activity, and a poor induction of lymphokine-activated killer (LAK) cell activity (following in vitro treatment with recombinant interleukin-2 [rIL-2]) have been detected. Recently, however, it has been demonstrated that perilymphatic injections of low doses of rIL-2 may induce a local reduction of tumor masses in these patients. The present study, a cooperative pilot effort on the clinical effects of this route of administration, showed an activation of the lytic machinery in lymphocytes belonging to the T-cell lineage, as well as a potentiation of NK activity in the peripheral blood. These findings demonstrated that the severe immunodeficiency of HNSCC patients may be at least partially corrected by in vivo administration of rIL-2.

Aged↗

Streptomycin perfusion of the labyrinth.

The combination of fluctuant hearing loss, fullness, tinnitus and dizzy spells we call Meniere's disease is thought to be caused by endolymphatic hydrops. Most patients with the clinical picture of Meniere's disease do have endolymphatic hydrops but some patients with endolymphatic hydrops do not have the clinical picture of Meniere's disease. It would appear there is an, as yet unknown, immune-mediated, cause for Meniere's disease, in addition to endolymphatic hydrops, and this immune-mediated cause may aggravate those ears with endolymphatic hydrops. While medical treatment with a low-salt diet, diuretics and steroids are of value in some patients when given early in controlling dizzy spells and improving the hearing, there is usually no real, long-term benefit. Since none of these "shunts" of the sac could remain open for more than a few hours, they could have no more direct benefit than a one-time drainage of endolymph, while doing harm to the fluid absorption, immune response and phagocytosis roles of the endolymphatic sac. The various vestibular neurectomy operations, while usually stopping the dizzy attacks, are both difficult and potentially dangerous, but more important, do nothing for the hearing loss. The one direct attack on the problem, both easy to perform and certain to relieve the dizzy attacks, is to destroy the vestibular receptors with streptomycin. This destructive action on the stereocilia and sensory cells, without damage to the rest of the vestibular system and the cochlea, has been verified by two cat experiments with streptomycin by Norris et al. and Norris & Shea and two guinea pig experiments with gentamicin by Kimura.(ABSTRACT TRUNCATED AT 250 WORDS)

Ear, Inner↗