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Biomedical subjects

C L Witte

Publications and source records attributed to C L Witte.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phenotypic and genotypic heterogeneity in familial Milroy lymphedema.

Familial Milroy lymphedema (ML) is classified as an autosomal dominant disorder characterized by peripheral edema of the lower extremities at birth or in early childhood. The variety of phenotypes are not well described, and the genomic location and functional expression of the gene or genes underlying this and related familial lymphedema syndromes remain largely unknown. In this collaborative study between the University of Arizona and the University of São Paulo, we collected clinical pedigrees on 6 ML families, carried out clinical examination of affected and unaffected individuals, and, in representative affected members of two of the families performed dynamic lymphangioscintigraphy (LAS) of the lower and upper limbs to delineate further the ML lymphangiodysplastic phenotype. To localize the gene for ML, we conducted a genome-wide search in 4 of the families using 387 polymorphic dinucleotide-repeat markers at approximate 10 cM spacing in 54 subjects (affected, unaffected bloodline relatives, and spouses). In all 6 families (86 subjects), we specifically examined the suggested linkage to the vascular endothelial growth factor (VEGF)-C receptor (Flt4) gene localized to the chromosome region 5q34-q35. The findings provide evidence for a spectrum of ML clinical and LAS phenotypes and also suggest ML locus heterogeneity.

Arizona↗
PubMed1995

Disorders of lymph flow.

Disturbances in blood capillary exchange of fluid, macromolecules, and cells across intact and abnormal microvessels and deranged lymphatic transport are integral, interacting components in disorders of tissue swelling. Lymphedema or low-output failure of the lymph circulation is often indolent for many years before lymphatic insufficiency (failure) and tissue swelling emerge and persist. Superimposed occult or overt infection (lymphangitis) are probably major contributors to progressive limb deformity (elephantiasis). Long-standing lymphedema is characterized by trapping in the skin and subcutaneous tissue of fluid, extravasated plasma proteins, and other macromolecules: impaired immune cell trafficking; abnormal processing of autologous and foreign antigens; heightened susceptibility to superimposed infection; local immunodysregulation; defective lymphatic (lymphangion) propulsion from an imbalance of mediators regulating vasomotion; soft-tissue overgrowth; scarring and hypertrophy; and exuberant angiogenesis occasionally culminating in vascular tumors (Fig. 8). In contrast to the blood circulation, where flow depends primarily on the propulsive force of the myocardium, lymph propulsion depends predominately on intrinsic truncal contraction, a phylogenetic vestige of amphibian lymph hearts. Whereas venous "plasma" flows rapidly (2-3 l/min) against low vascular resistance, lymph flows slowly (1-2 ml/min) against high vascular resistance. On occasion, impaired transport of intestinal lymph may be associated with reflux and accumulation and leakage of intestinal chyle in a swollen leg. Although the term "lymphedema" is usually reserved for extremity swelling, the pathogenesis of a wide variety of visceral disorders also may be traceable to defective tissue fluid and macromolecular circulation and impaired cell trafficking of lymphocytes and macrophages. Thus, lymph stasis, with impaired tissue fluid flow, underlies or complicates an indolent subclinical course with a long latent period and sporadic episodes of lymphangitis, which culminates in intense scarring. Examples are pulmonary fibrosis (e.g., pneumoconiosis), regional enteritis, retroperitoneal fibrosis, and perhaps chronic pancreatitis and cirrhosis of the liver. Transdifferentiation and ultimately transformation of endothelial and other vascular accessory cells during lymph stasis also may be pivotal to a wide range of dysplastic and neoplastic vascular disorders, including Stewart-Treves angiosarcoma, AIDS-associated Kaposi's sarcoma, and lymphangitic metastatic carcinomatosis. Lymphscintigraphy has now replaced conventional lymphography as the procedure of choice to corroborate the diagnosis of peripheral lymphedema, whereas MR imaging using paramagnetic and superparamagnetic contrast agents has the potential to yield huge dividends in furthering understanding of a variety of enigmatic edematous states, including lymphedema. Not only are better explanations and insights into swelling disorders likely to be forthcoming, but, equally important, these new, safe, noninvasive imaging techniques can and should be used to monitor the evolution and document the efficacy of commonly advocated operations and nonoperative remedies for defective lymph transport and function.

Diagnostic Imaging↗
PubMed1995

Percutaneous sclerotherapy of lymphangiomas.

PURPOSE: The authors report their experience with percutaneous image-guided sclerotherapy for treatment of unresectable lymphangiomas. MATERIALS AND METHODS: Five patients with unresectable lymphangiomas of the pelvis (n = 2), neck (n = 1), abdomen (n = 1), or leg (n = 1) were treated at two medical centers with sclerotherapy, with use of doxycycline as the sclerosant. Computed tomography was used to guide the procedures, with supplemental lymphoscintigraphy, ultrasound, and magnetic resonance imaging used as needed. RESULTS: Symptomatic relief of lymphedema, lymphorrhea, or a decrease in size of lymphatic pools was achieved, to varying degrees, in the five patients. Follow-up is ongoing, and further sclerotherapy may be indicated as the clinical course dictates. CONCLUSION: Percutaneous sclerotherapy with doxycycline is safe and appears effective for palliative treatment of unresectable lymphangiomas on the basis of our initial clinical experience.

Adolescent↗
PubMed1994

Kaposi's sarcoma, vascular permeability, and scientific integrity.

On March 13, 1992, Nakamura et al published an article in the journal Science reporting that sulfated polysaccharide peptidoglycan (SP-PG) inhibited the growth and vascular hyperpermeability characteristics of Kaposi's sarcoma-related cells and lesions in nude mice. While examining their key composite Fig 3, A through E, and related Table 2, we were surprised by several photographic features and other irregularities in the figures, which we explored further through a series of experiments. We were unable to confirm some of the pivotal findings. We communicated our concerns to Science but our letter was rejected. After submission of additional analysis, the matter was reopened by Science, but again our correspondence was rejected. Despite extensive review, the salient points raised in our initial correspondence remain unanswered or only tangentially addressed. The original conclusions by Nakamura et al are still not only highly dubious, but the validity of the peer review process and self-correcting nature of scientific inquiry are also called into question.

Animals↗
PubMed1993

Lymphatic abnormalities in human filariasis as depicted by lymphangioscintigraphy.

BACKGROUND: Investigation into filarial lymphedema has been hampered by the lack of a simple, safe, and easily repeated test to image the peripheral lymphatic system. Recent refinements in radionuclide lymphangioscintigraphy have established this noninvasive technique as the initial procedure of choice for visualizing lymphatics. Accordingly, we applied lymphangioscintigraphy to patients with filariasis and, for purposes of interpretation, compared the findings with those in patients with non-filarial lymphedema. METHODS: Thirty-three patients with classic symptoms or signs consistent with acute or chronic filariasis underwent lymphangioscintigraphy, and the findings were compared with those in five patients without lymphatic dysfunction and in 50 other patients with primary or secondary lymphedema without exposure to filariasis. RESULTS: As in patients with nonfilarial lymphedema, scintigraphic abnormalities in the 33 patients with filariasis included delayed or absent tracer transport of the radiotracer (25 patients), tortuous and bizarre deep lymphatics (seven patients), dermal diffusion (15 patients), retrograde tracer flow (six patients), and faint or absent regional nodal visualization (14 patients). Even in patients with long-standing filarial lymphedema, peripheral trunks were often visualized (at least in part), and regional nodes and more central lymphatics sometimes filled after light exercise. In some of the latter patients, however, discrete lymphatic trunks were not detected. CONCLUSION: Lymphangioscintigraphy is a simple, safe, reliable, noninvasive method with which to examine the peripheral lymphatic system, including truncal and nodal abnormalities, in endemic populations with occult and overt lymphatic filariasis.

Adolescent↗
PubMed1993

Endothelial transdifferentiated phenotype and cell-cycle kinetics of AIDS-associated Kaposi sarcoma cells.

The nature of Kaposi sarcoma (KS) (vascular malignancy vs. discordant angiogenesis) and lineage of the progenitor cell remain unclear. Therefore, AIDS-KS enzyme isolate cultures were prepared from excised skin lesions. Endothelial marker positivity for Factor VIII related antigen (F8RAg), Ulex europaeus agglutinin (UEA), and angiotensin-converting enzyme (ACE) were determined by fluorescence microscopy (FM) and flow cytometry (FCM). DNA cell-cycle analysis was performed using FCM. KS lesions showed large thick-walled channels (F8RAg and UEA strongly +), narrow vascular slits and thin-walled lakes (F8RAg and UEA weakly +), and non-prominent spindle cells (F8RAg and UEA almost uniformly negative). KS cultures yielded heterogenous populations of spindle, stellate, and flattened endothelial-like cells, displaying positivity for F8RAg (64 +/- 3%; mean +/- SE), UEA (40 +/- 9%), and ACE (81 +/- 9%). When injected subcutaneously in the nude mouse these cells failed to produce tumors. During contact inhibition induced quiescence, KS cultures exhibited a high G2M (18 +/- 3%) compared to non-KS (7 +/- 4%; p < 0.04), evidence of an altered proliferative potential consistent with a transdifferentiated or transformed phenotype.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Magnetic resonance imaging in human lymphedema: comparison with lymphangioscintigraphy.

Magnetic resonance (MR) imaging and isotope lymphography (lymphangioscintigraphy, LAS) was done in 32 patients with peripheral lymphedema (19 primary and 13 secondary). MRI characteristically showed diffuse dermal and subcutaneous edema, a nonedematous, occasionally hypertrophied skeletal muscle compartment, variability in regional lymph node size and appearance depending on the underlying clinical disorder, serpiginous "channels" or "lakes" consistent with dermal collateral lymphangiectasis and sequestered lymph, and increased subcutaneous fat. In contrast, LAS showed dermal diffusion ("backflow"), cross-over with retrograde tracer backflow (reflux), delayed tracer transport, and depending on the cause of lymphedema (i.e., primary or secondary), discrete or poorly defined lymph trunks (tracer "bands") and delayed or nonvisualization of regional lymph nodes. Although not a first-line clinical test, MR particularly in conjunction with LAS noninvasively provides accurate anatomical definition of the peripheral lymphatic system. In contradistinction to LAS, MR can visualize lymph trunks, nodes, and soft tissues proximal to sites of lymphatic obstruction. Together these imaging modalities may substitute for conventional oil contrast lymphography in the evaluation of the pathogenesis and evolution of most lymphologic disorders.

Adolescent↗
PubMed1992

Lymphatic imaging in experimental filariasis using magnetic resonance.

RATIONALE AND OBJECTIVES: To evaluate acquired lymphatic abnormalities caused by filariasis, the authors examined the peripheral lymphatic system in normal ferrets and those chronically infected with Brugia malayi using magnetic resonance imaging (MRI). The findings were compared with previously obtained lymphangioscintigraphic (LAS) images in ferrets both with and without experimental filariasis. METHODS: Fifteen ferrets (11 infected with B. malayi and four noninfected controls) underwent whole body coronal MRI using a quadrature transmission-receive head coil at 0.5 Tesla operating at a resonant frequency of 21.5 mHz for protons with a 25-cm field of view. RESULTS: In contrast to normal animals, infected ferrets showed dilated hindlimb dermal lymphatic collaterals, enlarged high-signal intensity groin lymph nodes with punctate low-signal intensity centers and separate low-signal intensity spots with irregular thin channels, suggestive of nests of viable adult nematodes within tortuous lymphatics and nodes. MRI correlated with the LAS findings, and the interpretations were supported by light, scanning electron, and video microscopy. CONCLUSIONS: T2-weighted MRI in conjunction with LAS accurately depicts the peripheral lymphatic system in filarial-infected ferrets. These two modalities are useful complementary techniques to examine disorders characterized by lymphatic insufficiency.

Animals↗