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Biomedical subjects

E Lewis

Publications and source records attributed to E Lewis.

At least 73 records · Page 4Linked to original sources

Contribution of hepatic fibronectin synthesis to regulation of plasma fibronectin.

Intravenous injection of gelatinized particles, which are phagocytized by the reticuloendothelial system, elicits an acute depletion of plasma fibronectin followed by restoration to normal concentrations in 6-8 h and a rebound elevation at 24 h. We determined the contribution of hepatic fibronectin synthesis to the restoration of plasma fibronectin in rats after particle infusion by measuring the net incorporation of 75selenomethionine into plasma fibronectin during the recovery period. Rats injected intravenously with gelatinized particles had a greater (P less than 0.01) incorporation of labeled 75selenomethionine into fibronectin but less (P less than 0.05) incorporation of 75selenomethionine into total plasma protein than control rats. Inhibition (86%) of hepatic fibronectin synthesis by pretreatment with cycloheximide limited the recovery of fibronectin levels by only 60%, suggesting a source(s) other than hepatic synthesis may contribute to the restoration of plasma fibronectin. Using purified human plasma fibronectin as a tracer in the plasma pool, we found that 26% of the soluble fibronectin consumed from the plasma during particle clearance was subsequently released back into the plasma over a 4-h interval. Tissue analysis indicated that 125I-labeled fibronectin, which was previously incorporated into the tissues, was not released from the tissue pool after the injection of gelatinized particles. Thus the normalization and regulation of plasma fibronectin levels after its acute depletion due to blood-borne particles is a result of 1) an increase in hepatic synthesis of fibronectin, 2) the release of fibronectin previously consumed as an opsonin during particle clearance, and 3) the release of soluble intact fibronectin from a preformed storage pool.

Animals↗

Fibronectin fragments in lung lymph after thrombin-induced lung vascular injury.

Fibronectin is an adhesive glycoprotein found in plasma and lymph as well as between lung endothelial cells and their collagenous basement membranes. Fibronectin is highly sensitive to proteolytic cleavage. We determined if fragments of fibronectin appear in lung lymph in association with increased lung protein clearance after thrombin-induced intravascular coagulation. Thrombin was infused intravenously, (80 units/kg for 30 minutes) into sheep (n = 8) surgically prepared with chronic lung lymph fistulas. Plasma and lymph fibronectin was assayed by electroimmunoassay. Fibronectin fragments were detected using Western blot analysis. After thrombin infusion, lymph flow increased 650% above baseline within 1-2 hours in association with a 35% decline in lymph-to-plasma total protein concentration ratio. This was followed by a second phase (3.5-6 hours) of normalized lymph-to-plasma ratios coupled with sustained elevation of lymph flow. Lung protein clearance remained elevated (p less than 0.10) for 5.5 hours. Plasma fibronectin levels declined slightly over 1-5 hours (zero time = 597 +/- 64 micrograms/ml; 1.5 hours = 478 +/- 59 micrograms/ml) and then increased significantly (p less than 0.05) over 24-48 hours (760 +/- 85 micrograms/ml). The amount of low molecular weight fibronectin fragments in lung lymph increased over the 1.5-6 hours post-thrombin and then declined over 12-48 hours. Thus after thrombin infusion, fragments of fibronectin were usually detected in increased amounts of lung lymph in association with an elevation of lung protein clearance.

Animals↗

Management of perinatal loss of a twin.

The death of a twin during pregnancy or around birth gives rise to a bewildering confusion of thoughts and feelings that can impede mourning and disturb the bereaved mother's care of a surviving twin. Every effort should be made to give the parents and siblings an experience of the dead baby. Photographs especially can reduce confusion and assist reality testing and thus facilitate the grieving process and improve the care of the surviving twin.

Bereavement↗

Viral oncolysates in patients with advanced ovarian cancer.

Viral oncolysates (VO) derived from two cultured ovarian carcinoma cell lines infected with influenza A/PR8/34 were administered intraperitoneally (IP) to 40 patients with advanced ovarian carcinoma, including 31 with late-onset ascites and 5 with pleural effusions. PR8 virus-specific antigens and ovarian tumor-associated antigens have been demonstrated on two oncolysates designated OVO1 and OVO2. Thirty-five patients received 9 mg of a 1:1 mixture of OVO1 and OVO2, 5 patients received one or the other. During the first month three IP schedules were evaluated, i.e., single, biweekly, and weekly, which were followed by monthly injections. Intrapleural (IP1) injections of a 3.0-mg 1:1 mixture of OV1 and OV2 were administered to 3 patients concurrently with initial IP injections and to 2 patients following later development of pleural effusions. In 7 patients ascites disappeared; in 5 of these the number of cytologically detected malignant cells was markedly reduced, in 1 pleural effusion disappeared, and in 3 tumor masses were reduced. Tumor masses shrank also in 2 patients without ascites. Tumor reduction conformed to standard response criteria in 2 of the 5 patients. Response duration in the 9 responding patients lasted from 3 to 19 months and survival durations 4 to 42 months. Disease symptoms in 7 patients improved noticeably. Two of the 9 responders later developed unilateral pleural effusions that responded for 7 and 15+ months to a single IP1 injection. Seventeen patients experienced one or more treatment side effects including fever, nausea or anorexia, malaise, abdominal pain, and arthralgia, but in only 2 patients, both on the weekly schedule, was toxicity severe enough to require treatment withdrawal. Humoral responses to viral and tumor cell-surface antigens were frequently observed in patients demonstrating clinical activity.

Adult↗

Effect of fibronectin-rich human cryoprecipitate on fluid volume requirements in sheep during postoperative sepsis.

Septic surgical patients often require fluid administration to maintain cardiovascular stability due, in part, to the sepsis-induced increase in vascular permeability and associated plasma volume depletion. Plasma fibronectin deficiency exists in such septic patients. We determined if maintenance of fibronectin levels by administration of fibronectin-rich human plasma cryoprecipitate would lower the resuscitative fluid volume needed for support of arterial pressure in septic postoperative sheep which were experimentally depleted of plasma fibronectin. Following a 2-hr postoperative baseline period, denatured collagen (gelatin, 8.7 mg/kg), which has a high affinity for fibronectin, was infused into both control and experimental sheep in order to acutely deplete plasma fibronectin. Sheep were then challenged both intraperitoneally and intravenously with live Pseudomonas (5 x 10(10) bacteria IP; 5 x 10(9) bacteria IV). Experimentals were given fresh plasma cryoprecipitate intravenously at a dose of 4 units bolus, followed by 3 units/hr for 5 hr. Controls received plasma cryoprecipitate selectively depleted of fibronectin by affinity chromatography. Bacterial challenge rapidly resulted in severe systemic hypotension. Ringer's lactate was infused intravenously into both groups at a rate sufficient to maintain a systemic arterial pressure of approximately 50 mm Hg with a maximum pulmonary artery wedge pressure of 15-18 mm Hg. Its rate of infusion was periodically adjusted to maintain this hemodynamic status. Comparison was made of the volume of Ringer's lactate required to maintain an arterial pressure of 50 mm Hg in both groups. Net fluid requirement was significantly (p less than 0.05) less in postoperative septic sheep (47.4 +/- 6.2 mg/kg/hr) treated with fibronectin-rich cryoprecipitate compared to the fluid requirement (71.7 +/- 4.7 mg/kg/hr) for postoperative septic sheep receiving fibronectin-deficient cryoprecipitate. Thus elevation of plasma fibronectin concentration lowers the fluid requirements needed for hemodynamic support in postoperative Gram-negative sepsis.

Animals↗

The use and abuse of imaging in gynecologic cancer.

The radiologic detection in staging of gynecologic malignancies comprises a variety of noninvasive and invasive procedures. In the last few years, the emergence of the cross-sectional imaging techniques such as ultrasonography (US), computerized tomography (CT), and more recently, magnetic resonance imaging (MRI) have enabled the radiologist to determine more accurately the entire degree and extent of pathologic processes both within the pelvis and spread of disease outside the pelvis. The radiologist has also become more involved in invasive procedures such as percutaneous biopsies, aspirations of fluid collections, and transcatheter intraarterial infusion and occlusions. Although the newer imaging modalities will be emphasized, an attempt will be made to point out both their strengths and weaknesses relative to the older modalities. The discussion will concentrate on ovarian and cervical cancers while the other cancers of the female genital tract will be superficially discussed. The thrust of the presentation will emphasize the workup of gynecologic patients, that the workup may be quick, thorough, and as practical as possible.

Diagnostic Imaging↗

Computed tomography of rectal and perirectal disease in AIDS patients.

Twenty-eight homosexual men with Kaposi sarcoma as part of the acquired immune deficiency syndrome (AIDS-related KS) and 2 homosexual men without AIDS were examined with abdominal and pelvic computed tomography (CT). Abnormalities of the rectum and perirectal areas were seen in 8 of the 30 patients on CT examination. Endoscopy and biopsy of the colon in these 8 cases revealed inflammatory changes in 6 patients and KS in 2. The CT abnormalities were not specific for inflammatory disease or tumor, and endoscopy with biopsy was necessary to establish an accurate diagnosis.

Acquired Immunodeficiency Syndrome↗

Renal sarcoma and sarcomatoid renal cell carcinoma: CT and angiographic features.

Computed tomographic (CT) and angiographic findings in 14 patients (eight men, six women, aged 30-72 years) with sarcomatoid renal cell carcinoma (SRCC) and various types of renal sarcoma are described. There were four patients with SRCC; three, leiomyosarcoma; two, liposarcoma; two, fibrosarcoma; and one each of unclassified renal sarcoma, clear cell sarcoma, and malignant fibrous histiocytoma. The most frequent presenting symptom was an abdominal mass or pain. All 14 patients underwent CT, and 11 underwent selective renal angiography. The diagnosis of renal sarcoma should be suspected when CT findings suggest that the tumor arises from the renal capsule or renal sinus and when the tumor is hypovascular or avascular on angiograms. The characteristic negative attenuation values for liposarcomas permit a specific diagnosis. Sarcomas that originate in the renal parenchyma and SRCC cannot be easily differentiated from renal cell carcinoma; however, renal sarcomas do not appear to have a propensity for extension into the renal vein or the inferior vena cava.

Adult↗

Plasma fibronectin therapy and lung protein clearance with bacteremia after surgery.

Plasma fibronectin modulates macrophage phagocytic function and can also incorporate into the insoluble tissue pool of fibronectin where it influences endothelial cell adhesion and tissue integrity. We studied the effect of postoperative bacteremia on lung protein clearance in relation to plasma fibronectin levels using the unanesthetized sheep lung lymph fistula model and the effect of infusion of purified human plasma fibronectin on lung protein clearance. Sheep received live Pseudomonas aeruginosa (5 X 10(8) iv) at a time of normal plasma fibronectin (590 +/- 37 micrograms/ml) or 5 days later at a time corresponding to elevation of plasma fibronectin (921 +/- 114 micrograms/ml). After the first bacterial challenge, there was a 22% decrease (P less than 0.05) in plasma fibronectin. Lung lymph flow (QL) initially increased 308% (P less than 0.05) by 2 h (0 h = 4.7 +/- 1.1 ml/h; 2 h = 14.4 +/- 3.5 ml/h), and the total protein lymph-to-plasma concentration ratio (L/P) declined. This was followed by a sustained second phase response over 3-12 h which was characterized by a 202-393% elevation in QL (P less than 0.05), an increase in the L/P ratio, and a 240-480% (P less than 0.05) increase in lung transvascular protein clearance (TVPC = QL X L/P). Sheep with elevated fibronectin levels also manifested the early (2 h) elevation in QL (P less than 0.05) coupled with a decline in L/P ratio after the second bacterial challenge, but the second-phase increase in TVPC was markedly attenuated. Intravenous infusion of 500 mg of human plasma fibronectin into normal sheep to elevate the fibronectin level comparable to that in the hyperfibronectinemic sheep also attenuated (P less than 0.05) the second-phase (3-12 h) increase in lung protein clearance with sepsis. Thus elevation of plasma fibronectin during postoperative Gram-negative bacteremia may protect the lung vascular barrier. This response may be mediated by either fibronectin's opsonic support of phagocytic function or its influence on lung endothelial cell adhesion.

Animals↗

Detection of herpes virus genome in Alzheimer's disease by in situ hybridization: a preliminary study.

The hypothesis that the limbic predilection for the histopathological lesions of Alzheimer's disease may be due to reactivation of Herpes simplex virus from the trigeminal ganglia is being tested by in situ hybridization, utilizing post mortem tissues harvested in a longitudinal study of this organic dementia. Techniques demonstrating Herpes virus DNA with sensitivity in the subgenomous range have already shown that this common viral agent resides in latent form within the Gasserian neurones of aged individuals. The possibility that such material when reactivated could travel via trigeminal branches to the medial temporal lobe of the human brain is under investigation.

Aged↗

Computed tomography findings of severe mineralizing microangiopathy in the brain.

The intracranial CT findings of mineralizing microangiopathy, a rare condition, are described in seven patients. The underlying pathology was posterior fossa medulloblastoma (four patients), cerebelloastrocytoma (two patients), and acute lymphatic leukemia (one patient). Each of the seven patients was less than 10 years old. Dystrophic calcification was present in the corticomedullary junction, lentiform nucleus of the basal ganglia, corticomedullary junction, and dentate nucleus of the cerebellum. Three of the patients had subtle neurologic signs related to the mineralizing microangiopathy, but none died of central nervous system disease. Although three factors--radiation therapy, chemotherapy, and increased intracranial pressure--probably have a synergistic role in the pathogenesis, radiation is believed the dominant factor. The minimum dose required to induce this damage is 2000 rad.

Astrocytoma↗