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Biomedical subjects

J Silva

Publications and source records attributed to J Silva.

At least 199 records · Page 11Linked to original sources
PubMed1987

Effect of hyperthermia on the sensitivity of human colon carcinoma cells to mitoxantrone.

The effect of temperature on the cytotoxicity of mitoxantrone (MX) was investigated by exposing human WIDR colon carcinoma cells to elevated temperatures in the presence of drug. The survival of treated cells was determined by their ability to proliferate and to form colonies in vitro. It was demonstrated that incubation of WIDR cells with MX at 42 degrees C produced not only a higher toxicity but also a more rapid action than when cells were exposed to drug at 37 degrees C. By measuring the amounts of 3H-MX incorporated by treated tumor cells, it was shown that cells at 42 degrees C induced an approximately threefold increase in drug uptake when compared to cells at 37 degrees C. The effect seemed long-lasting but preheating did not induce tolerance to a subsequent exposure to MX hyperthermia. Therefore, it is clear that the cytotoxic potency of MX can be augmented by elevated temperature possibly by enhancing the uptake of drug. The present findings may prove useful for designing an effective clinical regimen of MX thermochemotherapy.

Carcinoma↗
PubMed1986

The mechanism of action of 3,6-bis(2-piperidinoethoxy)acridine trihydrochloride (CL 246,738) in the potentiation of natural killer cells.

An effort has been made to determine the mechanism by which the immunomodulator 3,6-bis(2-piperidinoethoxy)acridine trihydrochloride (CL 246,738) enhances the cytotoxic activity of natural killer (NK) cells. Orally administered CL 246,738 produced augmentation of NK cell activity in mice in a dose-related fashion over a dose range of 10 to 160 mg/kg, with a peak stimulation occurring at 40 mg/kg. The stimulatory effect was short-lived and only persisted for 3 days after a single oral dose of the drug. However, it could be boosted by a subsequent treatment. With anti-asialo GM-1 (anti-ASGM-1) antibody used as an NK cell marker, it was determined that the compound increased the number of ASGM-1-positive cells in mice, as indicated by radioimmunoassay and immunofluorescence staining. NK cells of beige mice were also activated by CL 246,738. Furthermore, the compound at concentrations of 0.02 to 0.2 microgram/ml induced NK cell activity in vitro, with a minimum 3-day incubation being required for optimal activation. This effect was dependent on the presence of macrophages and was inhibited by anti-IFN-alpha + beta but not anti-IFN-beta antibody. Taken together, it is postulated that the compound functions by stimulating macrophages to release IFN-alpha, which subsequently activates NK cells. As an effective stimulator of IFN and NK cells, CL 246,738 may prove clinically useful in the immunotherapy of certain types of malignancy.

Acridines↗
PubMed1986

Inhibition of the induction of alloreactivity with mitoxantrone.

A clinically active anticancer agent, mitoxantrone (MX): 1, 4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9, 10-anthracenedione dihydrochloride, was studied for its potential inhibitory effect on alloreactivity induction. Addition of MX to mixed lymphocyte cultures (MLC) not only inhibited the proliferative response of lymphocytes to alloantigens but also prevented the generation of cytolytic T lymphocytes (CTL). MX showed a long-lasting effect in vitro and acted at the inductive rather than the effector phase of the CTL response as indicated by its failure to alter the activity of those CTL already generated in MLC. MX also inhibited CTL induction in mice. However, the precursors of CTL appeared to be spared in these animals as supported by limiting dilution analysis and also because CTL could be reactivated by exposure of splenocytes to the same or different alloantigens in MLC. The present findings demonstrate that MX is a potent immunosuppressive agent and as such might prove to be clinically useful in the treatment of autoimmune diseases or find utility in the organ transplantation field.

Animals↗
PubMed1986

Stimulation of enzyme secretion from isolated pancreatic acini by Clostridium difficile toxin B.

Exposure of isolated rat pancreatic acini to increasing concentrations (10 ng - 800 ng/ml) of toxin B from Clostridium difficile produced a biphasic effect on the rate of secretion of amylase, trypsinogen, and chymotrypsinogen. Whereas doses of toxin B from 10-30 ng/ml increased enzyme secretion by 15-20%, doses between 30 ng and 60 ng/ml showed a regression of this effect, whereafter the rate of secretion of amylase, trypsinogen, and chymotrypsinogen increased with increasing concentrations of the toxin. Toxin B concentration of 800 ng/ml enhanced amylase, trypsinogen and chymotrypsinogen secretion by 119%, 185% and 195%, respectively, when compared with the basal level. Stimulation of enzyme secretion by toxin B was not affected by the presence of either actinomycin-D or cycloheximide, at a concentration which inhibited acinar RNA or protein synthesis by 80-90%. Although toxin B as well as CCK8, carbachol and secretin by themselves caused significant stimulation in amylase, trypsinogen and chymotrypsinogen secretion from isolated pancreatic acini, toxin B together with either CCK8, carbachol or secretin produced no further augmentation in enzyme secretion than what was observed with the secretagogues alone. It is concluded that toxin B of Cl. difficile exerts a direct effect on pancreatic acinar cells as evidenced by stimulation of enzyme secretion.

Amylases↗
PubMed1986

Malakoplakia of the urinary tract.

The authors report 4 cases of urinary tract malakoplakia. This rare disease of unknown etiopathogenesis can present with a benign character in the bladder, but when the upper urinary tract is affected, loss of renal function can occur. Treatment aims to control the primary infection, as well as enhance intracellular bactericidal activity, which seems to be compromised in these cases. Cytoreductive surgery may be indicated when this treatment fails.

Child↗
PubMed1986

Depression, urinary free cortisol excretion and lymphocyte function.

An impairment in lymphocyte response to mitogen stimulation, a correlate of cell-mediated immunity, has been reported in patients with depressive illness. To investigate whether such impairment in lymphocyte function is related to excessive secretion of cortisol, an immunosuppressive hormone, we compared mitogen-induced lymphocyte proliferation in three groups of subjects: depressed patients with elevated 24-hour urinary free cortisol (UFC) excretion; depressed patients with normal UFC excretion; and normal controls. Depressed patients in both groups showed significant reductions in lymphocyte mitogenic activity, in comparison with the normal controls, but the two depressive groups did not significantly differ from each other in their lymphocytic responses to any of the mitogens used. Furthermore, no significant correlations were found, within depressed patients, between UFC excretion and lymphocyte mitogenic responses. Depression is therefore associated with an impairment in lymphocyte function that cannot be explained solely on the basis of increased cortisol secretion.

Depressive Disorder↗
PubMed1985

Etretinate therapy reduces polymorphonuclear leukocyte chemotaxis--enhancing properties of psoriatic serum.

Using a Boyden chamber technic, we measured the directed chemotaxis of polymorphonuclear leukocytes obtained from control subjects or psoriasis patients when the leukocytes were placed in sera obtained from control subjects or psoriasis patients. The samples from patients were obtained before therapy and after 2 and 4 weeks of etretinate administration. Compared with control sera, the sera from seven untreated psoriasis patients significantly enhanced the chemotaxis of polymorphonuclear leukocytes from control subjects toward a chemotaxin (p less than 0.05). After 4 weeks of etretinate therapy, the chemotaxis-stimulating ability of the sera from psoriasis patients was no longer significantly greater than that of the control sera. This decline in the chemotaxis-stimulating activity of our patients' sera preceded significant clearing of their psoriasis. The levels of circulating etretinate in the blood of our patients could not account for the reduction. Etretinate therapy had no apparent direct effect on the chemotactic activity of polymorphonuclear leukocytes from the psoriasis patients but may act in part by reducing the inflammatory effects of psoriatic sera.

Adult↗
PubMed1985

Acute pancreatitis.

The exocrine pancreas secretes into the gut on demand more than 20 proteins that are indispensable for digestion. In-vivo autodigestion is prevented by an array of natural safeguards. In acute pancreatitis, inappropriate intrapancreatic activation and release of pancreatic hydrolases occur, but the pathogenetic mechanism of autodigestion is unclear. The release of proteases, lipase and colipase, phospholipase A, vasoactive peptides, and other agents probably accounts for the edema, tissue destruction, fat necrosis, metabolic abnormalities, and complications. Ethyl alcohol abuse, gallstones, trauma, and other common and rare conditions can induce pancreatitis. The patient's outcome can be predicted by certain prognostic signs. Ultrasonography and computerized tomography are invaluable diagnostic tools and magnetic resonance imaging appears promising. Hemodynamic monitoring, intensive care with colloid and crystalloid infusions, correction of electrolyte abnormalities, judicious use of antibiotics, peritoneal lavage, drainage of pancreatic exudation fluids, and surgical intervention require a team approach, especially in patients with multiple complications. Additional research is needed into the pathogenetic mechanism of autodigestion and the design of specific therapies.

Abscess↗
PubMed1984

Transfer factor in the treatment of carcinoma of the lung.

From 1976 to 1982, 63 patients with carcinoma of the lung underwent curative pulmonary resection, mediastinal lymph node dissection, and postoperative mediastinal irradiation when indicated. After operation, the patients were randomized by cell type and stage of disease into two groups. Beginning 1 month postoperatively, Group 1 patients (N = 28) received 1 ml of transfer factor that had been extracted from the blood of normal individuals. Subsequent doses were administered at 3-month intervals. Group 2 patients (N = 35) served as controls. There were no significant differences between the two groups with respect to age, sex, extent of resection, histological cell type, or stage of disease. Twenty of the 28 treated patients were alive and free from disease from 7 to 77 months after treatment, whereas 17 of the 35 control patients were free from disease. The 1-year survival for Group 1 was 84% and for Group 2, 81%. The 2-year survival was 78% for Group 1 and 46% for Group 2 (p = 0.045). The survival rates by stage of disease were as follows: Stage I, 15 out of 17 or 88% in Group 1 and 15 out of 23 or 65% in Group 2 (p = 0.097); Stages II and III, 5 out of 11 or 45% in Group 1 and 3 out of 12 or 25% in Group 2 (p = 0.304). The results of the study suggest that the administration of transfer factor to patients who have undergone pulmonary resection for carcinoma of the lung can have a significant impact on the prolongation of life.

Adenocarcinoma↗
PubMed1984

Effect of therapy with latamoxef (moxalactam) on carriage of Clostridium difficile.

Twenty-seven patients receiving latamoxef (moxalactam) as a single antimicrobial agent were studied prospectively for Clostridium difficile carriage and development of diarrhoea or colitis. Stools were available prior to therapy from only seven patients, one of whom (14.3%) was an asymptomatic carrier. None of twelve patients studied during therapy were carriers. Seven of 27 patients (25.9%) were colonized with Cl. difficile after completion of latamoxef therapy, and three patients had cytotoxin positive stools. Two patients with cytotoxin grew Cl difficile from stools and one patient was culture negative. Only one patient, who had both culture and cytotoxin positive stools, had profuse diarrhoea. Cl. difficile clinical isolates were only moderately susceptible to latamoxef in vitro. Hamsters given moxalactam developed caecitis. Patients receiving latamoxef, or third generation cephalosporins, may be at increased risk of development of Cl. difficile associated diarrhoea and should be followed closely for this complication, especially after therapy has been discontinued.

Animals↗
PubMed1984

Resistance of Aeromonas hydrophila to beta-lactam antibiotics.

The activity of some beta-lactam antibiotics upon 20 strains of Aeromonas hydrophila and some properties of their beta-lactamases have been studied. High degree of resistance to benzylpenicillin and lower resistance to ampicillin and cephaloridine was observed. Clavulanic acid showed the highest activity. When clavulanic acid was assayed at subinhibitory concentrations in association with ampicillin. MICs of the latter decreased to two- to eight-fold. All strains produced inducible beta-lactamases with high activity upon ampicillin. A group of cephalosporinase-like enzymes was also found. Some beta-lactamases were inhibited by cloxacillin, and most of them were completely inhibited by 5 mg/l of clavulanic acid. Low impermeability of Aerom. hydrophila cells to beta-lactams was observed.

Aeromonas↗
PubMed1984

Treatment of antibiotic-associated colitis with vancomycin.

Sixty-five patients were treated with oral vancomycin for Clostridium difficile colitis associated with treatment of infection by antibiotics. Colitis was confirmed by endoscopy in patients with diarrhoea and positive tests on diarrhoeal stools for Cl. difficile and/or its cytotoxin or, if endoscopy could not be performed, by the presence of fever and peripheral or faecal leucocytosis. Vancomycin dosage ranged from 125 to 500 mg four times daily for an average of about ten days. The mean duration of diarrhoea after starting therapy was four days; abdominal pain and fever usually resolved in two or three days. Post-treatment carriage of Cl. difficile was common. Eighteen per cent of patients developed a recurrence of colitis after treatment was discontinued, but responded to treatment with oral vancomycin, metronidazole, or bacitracin. After comparison of our results with those reported by others we concluded that vancomycin remains the treatment of choice for patients who are acutely and severely ill with Cl. difficile.

Adult↗
PubMed1984

Colonization of central venous catheters.

We studied etiologic factors important in colonization of 179 central venous catheters (CVCs) in patients randomized into group 1 (who received daily topical applications of povidone-iodine) or group 2 (who received only dry dressing changes). Colonization rates of CVC tips were similar between group 1 (18/84 or 21%) and group 2 (22/95 or 23%). Peripheral blood cultures grew Candida in eight hyperalimented patients (evenly divided between groups 1 and 2), S epidermidis in four other patients (also evenly divided), and gram-negative bacteria in three patients. Colonization rates for CVCs in place for 0 to seven days was 15.6% (17/109) and 76.7% (23/30) if used from eight to 30 days. Inflammatory signs at CVC sites were often absent when CVCs became colonized or produced bacteremia. Unimportant determinants of CVC colonization included skin securement of CVCs, antibiotic infusions through CVC lines, and masking and gowning of physicians before CVC placement. Daily applications of povidone-iodine did not reduce colonization of CVCs as compared to dry dressing changes.

Administration, Topical↗
PubMed1984

Clinical competence certification: a critical appraisal.

The American Board of Internal Medicine has requested that residency program directors certify the clinical competence of their candidates. The clinical evaluation exercise (CEX) is one component of the overall certification process. During 1980-1982, 120 residents at the University of Michigan Hospitals participated in a CEX. The results show recurrent inadequacies among the residents in eliciting the social and family histories and performing the mental status and neurologic examinations. The ability to elicit a complete medical history correlated (p less than .01) with communication skills. In three of four specific organ examinations, the ability to perform a technically correct and complete physical examination correlated with the accuracy of the residents' findings (p less than .05). Separate evaluations by senior faculty members generally did not correlate with the residents' performance on the CEX. Analysis of the program described here showed that it requires considerable faculty time, requires training of evaluators to develop interrater reliability, and raises questions as to the validity of the CEX. As national certification boards integrate a formal clinical component into the certification process, such problems need to be addressed and rectified.

Certification↗