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Biomedical subjects

D Snyder

Publications and source records attributed to D Snyder.

At least 55 records · Page 3Linked to original sources

Reduction by anti-antibody administration of the radiotoxicity associated with 131I-labeled antibody to carcinoembryonic antigen in cancer radioimmunotherapy.

Radiolabeled antibodies have been shown to have a therapeutic potential in tumor-bearing animal models. However, treatment with radiolabeled antibodies results in toxic effects to normal tissues, as monitored by losses in body weight and in peripheral wbcs. We have investigated the use of an anti-antibody, or second antibody (SA), as a means of reducing this toxicity. SA rapidly forms a complex with circulating radiolabeled antibody, causing an increase in the clearance rate of the radiolabeled antibody from the blood. Toxicity was significantly reduced in animals given the SA in comparison to the toxicity seen in animals given only the radiolabeled primary antibody (PA). The earlier the SA was administered, the lower was the toxicity. The therapeutic efficacy of radiolabeled antibody was not influenced by the administration of the SA given 48 hours after the PA. Thus, the controlled removal of circulating radiolabeled antibody by an anti-antibody can reduce the toxicity associated with radiolabeled antibody therapy without influencing the antitumor effect.

Animals↗

Platelet survival in patients with beta-thalassemia.

Thromboembolic events associated with significant morbidity and mortality have been observed in patients with beta-thalassemia major (TM). These include arterial as well as venous thrombosis and the development of early arteriosclerosis. To elucidate the possibility that TM patients may develop a hypercoagulable state we carried out a study of platelet kinetics on ten patients with TM and four patients with thalassemia intermedia (TI). Autologous platelets were labeled with indium-111-oxine, and the platelet lifespan (PLS) was determined. A significant shortening of PLS was observed in 13 out of 14 patients examined. The mean PLS (+/- 1 SD) in ten patients (8 TM, 2 TI) who underwent splenectomy was 107 +/- 36 hr (control splenectomized 248 + 51 hr) (P less than .001) and in four nonsplenectomized patients (2 TM, 2 TI) was 102 +/- 64 hr (control 224 + 23 hr) (P less than .01). The short PLS in addition to reported findings of increased circulating platelet aggregates and the decreased response of TM platelets to aggregating agents suggests in vivo platelet activation in thalassemic patients.

Adolescent↗

Effect of Na + flux inhibitors on induction of c-fos, c-myc, and ODC genes during cell cycle.

The role of Na + transport systems in the mitogenic signal induced by growth factors was studied, and it was shown that two Na + transport systems contribute to the early increase in cytoplasmic Na + in response to serum growth factors, namely the amiloride-sensitive Na+/H+ antiport and the bumetanide-sensitive Na+/K+/Cl- cotransport. Bumetanide or amiloride, when added separately, inhibited part of the increase in cytoplasmic Na +, as a response to the addition of serum to quiescent BALB/c mouse 3T3 fibroblasts. Each drug also suppressed part of the stimulation of the ouabain-sensitive Rb + influx, which was controlled by intracellular Na +. However, when both drugs were added together with serum growth factors, a complete inhibition of the early increase in [Na +], and subsequently a complete blockage of Na+/K+ pump stimulation was obtained. Amiloride or bumetanide, when added separately, only partially inhibited DNA synthesis induced by serum, 24% and 8% respectively. However, when both drugs were added together, at the time of serum addition to the quiescent cells, cell entry into S-phase was completely inhibited. To investigate the mode of cell-cycle inhibition, analysis was done of the possible role of early Na + fluxes in the mitogenic signal transduced from cell membrane receptors to the nucleus. The effects of the two drugs amiloride and bumetanide on induction of three genes--c-fos, c-myc, and ornithin decarboxylase (ODC)--was measured during cell transition through the G1-phase. Amiloride and bumetanide, when added separately or in combination, did not inhibit the induction of c-fos, c-myc, and ODC mRNAs. These results suggest that stimulation of Na + fluxes by serum growth factors is essential for cell transition into the S-phase of cell cycle, but it plays no apparent role in the growth factor signal transduced from the cell surface to the interior of the cell, as manifested by c-fos, c-myc, and ODC genes induction.

Amiloride↗

Prevention and treatment of experimental prostate cancer in Lobund-Wistar rats. I. Effects of estradiol, dihydrotestosterone, and castration.

The Lobund-Wistar (L-W) rat is unique in its susceptibility to spontaneous and induced metastasizing prostate adenocarcinomas (PAs). A single IV inoculation of methylnitrosourea (MNU) produced PAs in 20% of L-W rats in 12 months. The combination of MNU plus two to seven slow-release implants of testosterone propionate (TP) induced PAs in 50-90% of rats respectively in an average of 11.5 months. The induction of PAs was prevented by early treatments of rats at risk with estradiol and less so with dihydrotestosterone (DHT). However, on a technical basis, the results were not significant. Treatments of MNU-inoculated rats with estradiol, with DHT, or by castration, at intermediate points in the projected latency time of tumor development, reduced significantly the incidences of PA development. Rats in which overt PAs had already developed in response to 12 months of exposure to implants of TP did not respond to treatment by estradiol, DHT, or castration. Thus there are early stage(s) in induced prostate tumorigenesis in L-W rats that are sensitive to modulating agents.

Adenocarcinoma↗

Laser angioplasty of totally occluded coronary arteries and vein grafts: preliminary report on a current trial.

CLINICAL PERSPECTIVE: Among the various laser angioplasty systems and atherectomy devices currently in clinical trials, the Lastac system appears to be particularly suitable for treating totally occluded coronary arteries and vein grafts. Preliminary results of a clinical trial in more than 35 patients show a recanalization rate of 92% and no complications attributable to the laser. Restenosis has occurred in five cases; in three of these, the arteries were reopened with laser or conventional angioplasty.

Angioplasty, Balloon↗

Amiloride added together with bumetanide completely blocks mouse 3T3-cell exit from G0/G1-phase and entry into S-phase.

In this study we tested the hypothesis that stimulation of univalent-cation fluxes which follow the addition of growth factors are required for cell transition through the G1-phase of the cell cycle. The effect of two drugs, amiloride and bumetanide, were tested on exit of BALB/c 3T3 cells from G0/G1-phase and entry into S-phase (DNA synthesis). Amiloride, an inhibitor of the Na+/H+ antiport, only partially inhibited DNA synthesis induced by serum. Bumetanide, an inhibitor of the Na+/K+ co-transport, only slightly suppressed DNA synthesis by itself, but when added together with amiloride completely blocked cell transition through G1 and entry into S-phase. Similar inhibitory effects of the two drugs were found on the induction of ornithine decarboxylase (ODC) (a marker of mid-G1-phase) in synchronized cells stimulated by either partially purified fibroblast growth factor (FGF) or serum. To test this hypothesis further, cells arrested in G0/G1 were stimulated by serum, insulin or FGF. All induced similar elevations of cellular K+ content during the early G1-phase of the cell cycle. However, serum and FGF, but not insulin, released the cells from the G0/G1 arrest, as measured by ODC enzyme induction. This result implies that the increase in cellular K+ content may be necessary but not sufficient for induction of early events during the G1-phase. The synergistic inhibitory effects of amiloride and bumetanide on the two activities stimulated by serum growth factors, namely ODC induction (mid-G1) and thymidine incorporation into DNA (S-phase), suggested that the amiloride-sensitive Na+/H+ antiport system together with the bumetanide-sensitive Na+/K+ transporter play a role in the mitogenic signal.

Amiloride↗

Coupling of a loop diuretic-sensitive Na+ influx with the net loop diuretic-sensitive K+ efflux in mouse NIH 3T3 cells.

Mouse 3T3 fibroblasts have a loop diuretic sensitive Na+ transport system, responsible for more than 50% of the total Na+ influx. This transport system is dependent on the simultaneous presence of all three ions; Na+, K+, (Rb+) and Cl- in the extracellular medium. The same requirement for these three ions was also found for the loop diuretic-sensitive K+ efflux. In addition, the sensitivities of Na+ influx and Rb+ efflux for the two loop diuretics, furosemide and bumetanide were found to be similar. The similar ionic requirement and sensitivity towards loop diuretics of the two fluxes, support the hypothesis, that this loop diuretic-sensitive Na+ influx in mouse 3T3 cells, is accompanied by the net loop diuretic-sensitive K+ efflux.

Animals↗

Cognitive subtypes in developmentally disabled children: a pilot study.

Differential diagnoses within the pervasive developmental disorders have insufficient reliability, validity, and descriptive homogeneity within groups to be used as distinct categories for research purposes. This study reports the results of cognitive subtyping of 54 developmentally disabled children. Fifty-one were successfully categorized in a small number of groups, characterized by different strengths and weaknesses on verbal, performance, memory, and quantitative tests. About half of the children had the relatively good visuospatial performance expected on the basis of previous literature on autistic children; these children were not behaviorally more autistic than the others. Measures of internal validity are reported, as well as validation by cognitive and behavioral variables. These results tentatively suggest that such psychiatric manifestations as autistic aloofness and maintenance of sameness may be relatively independent of cognitive skill patterns.

Adolescent↗

Ouabain-resistant Na+, K+ transport system in mouse NIH 3T3 cells.

It is shown that the ouabain-resistant (OR) furosemide-sensitive K+(Rb+) transport system performs a net efflux of K+ in growing mouse 3T3 cells. This conclusion is based on the finding that under the same assay conditions the furosemide-sensitive K+(Rb+) efflux was found to be two- to threefold higher than the ouabain-resistant furosemide-sensitive K+(Rb+) influx. The ouabain-resistant furosemide-sensitive influxes of both 22Na and 86Rb appear to be Cl- dependent, and the data are consistent with coupled unidirectional furosemide-sensitive influxes of Na+, K+ and Cl- with a ratio of 1:1:2. However, the net efflux of K+ performed by this transport system cannot be coupled to a ouabain-resistant net efflux of Na+ since the unidirectional ouabain-resistant efflux of Na+ was found to be negligible under physiological conditions. This latter conclusion was based on the fact that practically all the Na+ efflux appears to be ouabain-sensitive and sufficient to balance the Na+ influx under such steady-state conditions. Therefore, it is suggested that the ouabain-resistant furosemide-sensitive transport system in growing cells performs a facilitated diffusion of K+ and Na+, driven by their respective concentration gradients: a net K+ efflux and a net Na+ influx.

Animals↗

Steroid-induced ocular hypertension in patients with filtering blebs.

Four patients developed moderate to marked (25 to 42 mm Hg) elevation of intraocular pressure (IOP) while receiving chronic topical corticosteroids following filtration surgery. All of the eyes had good filtering blebs and no obvious reasons for the elevated IOP. The IOP dropped to 20 mm Hg or lower after the steroid drops were stopped. Our cases support the hypothesis that topical corticosteroid medication can cause an elevated IOP in eyes with functioning filtering blebs during the early postoperative period.

Adolescent↗

Hypoglossal nerve palsy in infectious mononucleosis.

Involvement of the central nervous system is a rare complication of infectious mononucleosis. Isolated cranial nerve palsy is the least reported neurologic complication. We report a second case of hypoglossal nerve palsy associated with infectious mononucleosis, and review 20 other reported cases of cranial nerve palsies. Any cranial nerve may be involved. The onset of the palsy usually follows the diagnosis and clinical presentation of infectious mononucleosis. The prognosis for a complete recovery is excellent, although recovery may be protracted. The use of steroids does not appear to be etiologic, nor beneficial or deleterious in treatment.

Adolescent↗

Corticosteroids for asthma during pregnancy.

This is a retrospective evaluation of 36 pregnant patients who required corticosteroids for control of their asthma. In view of the lack of maternal or infant abnormalities it is felt that corticosteroids should not be withheld from pregnant patients when required.

Asthma↗

Community oriented videotapes - action tools for health educators.

Over the last 4 years the Health Education Project (HEP) at the College of Medicine and Dentistry of New Jersey in Newark, New Jersey has established health education activities in the Outpatient Department waiting room of Martland Hospital and in various community settings. Bilingual, community-oriented videotapes are used consistently in these settings as teaching tools to inform consumers about critical health information. All videotapes are tailored to specific health education teaching objectives and are interwoven into health education discussion groups conducted by skilled group leaders.

Community Health Services↗

Doctor-patient communications in a private family practice.

One hundred fifty-five randomly selected patients in a private family physician's office were interviewed immediately before and immediately after their visit with the doctor in an attempt to assess the degree of misunderstanding that occurs in doctor-patient communications. Fifty-four percent of these patients either forgot to mention all their medical problems to the physician or they confused or forgot certain instructions concerning their diagnosis or treatment. A X2 analysis failed to reveal any significant sex or age differences in the proportions of misunderstandings. There was also no correlation between the number of misunderstandings, the amount of time the doctor spent with the patients, the patient's rating of their own health on a scale of one to ten, and the patients' complaints or praises about their medical treatment. The number of years of formal education completed by the patient showed a direct relationship to the number of misunderstandings. Patients on their first three visits to this office tended to misunderstand more of their medical instructions. Furthermore, the study suggested that patients with chronic internal diseases and those who express excessive trust in their physician might have an increased proportion of misunderstandings.

Adolescent↗