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Biomedical subjects

M H Witte

Publications and source records attributed to M H Witte.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1990

Quantitation of human melanoma, carcinoma and sarcoma tumor cell adhesion to lymphatic endothelium.

We have used an in vitro adhesion assay to study the interaction of tumor cells with lymphatic endothelium, a dynamic event that leads to tumor metastasis in vivo. 3H-thymidine-labeled human tumor cells from: one primary Ewing sarcoma, two established melanoma cell lines, two colon and two breast carcinomas (one established line and one primary culture of each) were added to 24-well culture dishes containing confluent monolayers of bovine lymphatic endothelium. Radioactivity associated with either the cells in suspension or the attached cells was assessed and compared at frequent intervals up to 360 minutes. Generally, tumor cell attachment increased as a function of time reaching a plateau between 180 and 360 minutes. the modular media system described here facilitates the primary and secondary culture (or co-culture) of a variety of normal and transformed cells. Primary cultures with a rounded morphology (one breast and one colon carcinoma) showed the lowest preferential attachment for lymphatic endothelium. All established cell lines and the primary Ewing sarcoma cell line displayed a more fibroblastic morphology and achieved the highest adhesion profiles. There was a correlation between the malignancy and attachment potential for the melanoma and breast carcinoma cell lines. Collectively, these data show that established tumor cell lines with fibroblastic-like morphology exhibit more rapid adhesion than primary tumor cell cultures with more rounded morphologies. While this property may reflect in vitro selection and/or adaptation, it does correlate with the metastatic propensity for some human tumor cells.

Adenocarcinoma↗
PubMed1990

AIDS, Kaposi sarcoma, and the lymphatic system: update and reflections.

Based on ongoing basic and clinical investigations, further evidence is presented that the AIDS-Kaposi sarcoma (AIDS-KS) complex involves a progressive disturbance of the blood-lymph circulatory loop of fluid, macromolecules, and migrating cells. We first surveyed the spectrum of vascular abnormalities including Kaposi sarcoma (KS) found in the AIDS/ARC population, then non-invasively imaged lymphatic system abnormalities in AIDS-KS by whole body lymphangioscintigraphy, and finally examined the biologic behavior of AIDS-KS cells in long-term tissue culture. These observations are viewed in terms of the lymphatic and blood vascular route of entry and transport of free and cell-associated virus and other opportunistic pathogens as well as poorly understood host endothelial-immune system interactions.

AIDS-Related Complex↗
PubMed1990

Effect of interleukin-2 on microvascular liquid and protein transport in the rat small intestine.

Interleukin-2 (IL-2), a glycoprotein lymphokine derived from activated T-lymphocytes displays potent anti-cancer properties but its therapeutic use has been limited by generalized tissue swelling. To shed light on the mechanism underlying this potentially life-threatening edematogenic syndrome, recombinant IL-2 or an equal volume of control solution (excipient or 5% dextrose) was administered to 88 adult, male Sprague-Dawley rats. Initially, rats were injected with 50,000 Cetus units (equal to 300,000 I.U.) of IL-2 intraperitoneally, either one-time ("acute" rats) or every eight hours for two or seven days ("chronic" rats). Thereafter, under pentobarbital anesthesia, the main mesenteric lymph duct was isolated, incised, and measurements made of intestinal lymph flow (JV) and the total protein content and protein fractions in lymph (L) and plasma (P) (refractometry and agarose gel electrophoresis, respectively). Final measurements were also carried out after superior mesenteric vein constriction to assess filtration-independent L/P total protein "washdown." After IL-2, JV and protein clearance (JV x L/P) were increased (p less than 0.001) while lymph and plasma total protein content and protein fractionation were unchanged. Protein washdown was also maintained. These data are not only inconsistent with bulk "plasma leak" from damaged capillaries, but in conjunction with previously demonstrated increased cardiac output and reduced systemic vascular resistance after IL-2 administration, the findings favor augmented microvascular surface exchange area from increased capillary perfusion as the primary mechanism underlying increased transcapillary liquid and protein flux. This conclusion conforms to the rapid reversal of edema in patients after cessation of IL-2 therapy.

Animals↗
PubMed1989

A curriculum on medical ignorance.

The information and technology explosions in medicine have exposed the vast realm of ignorance in human biology as well as the transiency of accepted knowledge and shortcomings of instructional methods which foster rote memorization, excessive reliance on conflicting data bases, and short-answer testing. To circumvent this serious deficiency in medical education, we have initiated a multifaceted Curriculum on Medical Ignorance consisting of 'questioning' seminars and hands-on clinical and laboratory experiences. This teaching programme not only emphasizes medicine's current deficiencies and limited insight into disease processes (i.e. ignorance) but also assists students in developing attitudes and behaviours to investigate basic biologic and clinical unknowns while rendering sound everyday clinical decisions in the face of fragmentary understanding. Based on evaluative feedback over the past 3 years, participants have made substantial progress towards recognizing and dealing constructively with medical ignorance and the limitations of 'knowledge of the day', thereby preparing them for the certain uncertainty of future medical practice.

Arizona↗