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Biomedical subjects

M H Witte

Publications and source records attributed to M H Witte.

At least 19 recordsLinked to original sources
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↗
PubMed1992

MR lymphography with iron oxide compound AMI-227: studies in ferrets with filariasis.

OBJECTIVE: The purpose of this study was to assess the MR lymphographic potential of AMI-227 to reduce the signal intensity of hyperplastic inflammatory lymph nodes by using ferrets with filariasis as the animal model. Both interstitial and IV modes of administration were studied. MATERIALS AND METHODS: Twelve ferrets were infected with the filaria Brugia malayi and six control ferrets were injected with super-paramagnetic iron oxide AMI-227, either interstitially or IV. Signal intensities of the left popliteal lymph node, left hamstring muscle, and left inguinal fat were measured before, 48 hr after, and up to 138 days after contrast injection with the use of both spin-echo and gradient-echo techniques. The signal intensity data were statistically analyzed. The lymph nodes, liver, spleen, and lungs were studied with light and electron microscopy. RESULTS: Forty-eight hours after the interstitial injection of AMI-227, the signal intensities of the ipsilateral popliteal nodes of the infected and control ferrets were significantly reduced (p less than .0005) without significant changes in the signal intensities of the surrounding tissues on both spin-echo and gradient-echo MR images. No nodal signal reduction occurred with the IV route of injection in ferrets. Light microscopy revealed iron to be localized within nodal marginal zones exclusively. Lymphatic trunks were visualized after interstitial injection. Signal reduction persisted to our end point at 138 days. CONCLUSION: AMI-227 shows regional specificity with significant enhancement of nodal structures and demonstrates potential as an interstitial MR lymphographic agent.

Animals↗
PubMed1991

Chaos and predicting varix hemorrhage.

Despite a wide array of mechanisms implicated in esophagogastric varix hemorrhage, predicting the onset of bleeding or even identifying the dominant factor in its causation has proved elusive. In this article we re-examine variceal pathophysiology and hypothesize that bleeding is rooted in turbulent portal system flow, a phenomenon embodied in the 'new' science of chaos and the principles of non-linear, rhythmic fluid dynamics. Analogous to forecasting the weather, predicting turbulent flow hinges on defining the initial physical conditions, and, like the field theory of quantum physics, depends on probabilities and instabilities rather than direct proportional analysis. Based on the complex regional and systemic hemodynamic forces and local physical properties underlying formation and perpetuation of esophagogastric varices, we propose, as with climatologic events, that a relatively minor or remote physiologic adjustment may set into motion a sequence of destabilizing splanchnic blood flow kinetics that ultimately causes a varix to erupt. In other words, the onset of varix bleeding derives from a sudden, erratic switch from disorganized but stable to disruptive turbulent variceal blood flow, and as a 'chaotic' phenomenon, is likely to remain for the foreseeable future highly unpredictable.

Biophysical Phenomena↗
PubMed1990

Plasma levels of fibronectin and prostacyclin metabolite in peripartum preeclamptic women.

Plasma fibronectin and prostacyclin levels have been reported to vary in preeclamptic women when compared with pregnant control women. Elevation of fibronectin and deficiency of prostacyclin have been postulated to be due to endothelial cell disruption or dysfunction. Eighteen preeclamptic women and 19 normal pregnant controls were evaluated for plasma levels of fibronectin and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). 6-keto-PGF1 alpha and fibronectin plasma levels in patients were significantly different from control patients, with preeclamptic patients exceeding control subjects. Five patients had serial samples of 6-keto-PGF1 alpha prior to, during, and after intravenous magnesium sulfate therapy and no consistent effect was noted. No correlation existed between fibronectin and 6-keto-PGF1 alpha levels or between either compound and platelet count or liver function tests. Despite an overall elevation of fibronectin in preeclamptic patients, two patients with the hemolysis, elevated liver tests, and low platelet count syndrome showed low normal fibronectin levels coinciding with thrombocytopenia, hemolysis, and liver dysfunction. The magnitude of fibronectin elevation may therefore not predict the severity of preeclampsia. The significance of these findings is discussed.

Adolescent↗
PubMed1990

Preeminence of lesser splanchnic blood flow in selected patients with generalized portal hypertension.

Although restricted transhepatic portal flow is necessary for development of generalized portal hypertension (GPH), increased splanchnic arterial inflow also contributes to GPH and its clinical sequelae. In this context, we describe 7 male and 6 female patients (mean age 48 years) in whom the lesser splanchnic (gastrosplenic) system played a key role in the signs and symptoms of GPH. These 13 patients (9 with hepatic cirrhosis, 3 with primary myeloproliferative disorder, and 1 with extrahepatic portal block) shared common features of massive splenomegaly, huge splenofundic gastric varices, often with a prominent natural shunt to the left renal vein. Total or near total splenectomy alone or combined where appropriate with coronary vein ligation was effective in controlling varix hemorrhage (10 patients), ascites (3), or complications of an enlarged spleen-anorexia and abdominal pain (3), hemolytic anemia (1) and profound thrombocytopenia with severe epistaxis (1). Intraoperative jejunal portal venography was crucial in operative management in order to establish definitively the presence or absence of coronary venous collaterals, and when present, to verify their operative ligation. These distinctive patients illustrate: 1) GPH is a heterogeneous syndrome of divergent splanchnic circulatory patterns, a feature which should be taken into account in selecting operative treatment; 2) one well-defined subgroup displays prominent hyperdynamic lesser splanchnic and specifically, splenic blood flow as a major contributor to clinical complications; and 3) within this subgroup, splenectomy combined with documented absence or surgical interruption of coronary venous collaterals as corroborated by intraoperative portography is effective alternative treatment.

Adolescent↗
PubMed1990

Lymphangioscintigraphy in AIDS-associated Kaposi sarcoma.

Kaposi sarcoma, a common opportunistic neoplasm complicating AIDS, is thought to arise from the vasculature and possibly from lymphatic endothelium. To evaluate the nature and extent of lymphatic involvement in AIDS-associated Kaposi sarcoma, we used an improved technique of whole-body lymphangioscintigraphy. Six human-immunodeficiency-virus-seropositive men (40-51 years old) with AIDS and extensive Kaposi sarcoma had bilateral foot and/or hand intradermal injection of 0.05 ml of 99mTc-labeled human serum albumin (500 microCi, 18.5 MBq). After sequential whole-body scanning with a digital gamma camera, the findings were interpreted by comparing them with findings from similar studies in 30 other patients without AIDS or Kaposi sarcoma (26 with primary or secondary lymphedema and four with normal extremities). Unlike in normal limbs, where lymphangioscintigraphy displayed early lymphatic truncal and regional nodal filling with radionuclide, in patients with Kaposi sarcoma, lymphangioscintigraphy disclosed a variety of abnormal patterns with some features distinct and others resembling lymphatic dysplasia as seen in primary and secondary lymphedema. These included focal accumulation of tracer within lymphatic channels in the distribution of cutaneous Kaposi lesions; delayed tracer transport with absent, faint, or intense regional lymph nodal uptake; and retarded or impeded lymphatic drainage with tracer intensification in the region of Kaposi sarcoma plaques. The impaired lymphatic drainage and nodal dysfunction seen on scintigrams in patients with AIDS-associated Kaposi sarcoma suggest a close connection between the lymphatic system and this disorder.

Acquired Immunodeficiency Syndrome↗