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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 433 records · Page 24Linked to original sources

Modification and evaluation of the potato disc assay and antitumor screening of euphorbiaceae seeds.

Galsky et al. (10, 11) have reported that the inhibition and growth of crown gall tumors, initiated on potato discs by Agrobacterium tumefaciens, apparently has good agreement with 3PS in vivo antileukemic activity in mice. We have now modified and evaluated this assay for its potential use as a prescreen and fractionation monitor of plant extracts for 3PS activity. The modified assay was performed on a series of natural compounds and plant extracts (known to have 3PS activity) and on extracts of seeds of 41 Euphorbiaceae species. The results suggest that the potato disc assay is a safe, simple, rapid, in-house, low cost, prescreen for 3PS antitumor activity; it detects some false positives, but few false negatives; it is statistically much more predictive (p = 0.002) of 3PS activity than either the 9KB (p = 0.140) or the 9PS (p = 0.114) cytotoxicity assays. Its extended use could easily obviate the expense and extensive need for animals in the initial stages of antitumor screening and plant fractionation.

Animals↗

Use of potato disc and brine shrimp bioassays to detect activity and isolate piceatannol as the antileukemic principle from the seeds of Euphorbia lagascae.

EtOH extracts of the seeds of Euphorbia lagascae inhibited crown gall tumors on potato discs, were active against 3PS (in vivo) and 9PS (in vitro) mouse leukemia, and were toxic to brine shrimp. Using the potato disc and brine shrimp bioassays to monitor fractionation, piceatannol (3,4,3',5'- tetrahydroxystilbene ) was isolated as the 3PS active principle. Aesculetin (6,7-dihydroxycoumarin) was isolated in large quantity, was weakly cytotoxic in 9KB , but was inactive in the other bioassay systems. Sucrose was also isolated. A combination of the simple crown gall and brine shrimp bioassays can thus be used both to detect and to isolate plant antitumor substances, minimizing the need for extensive antitumor testing in vivo.

Animals↗

Daphnane diterpenes from Diarthron vesiculosum: vesiculosin and isovesiculosin.

An alcoholic extract of Diarthron vesiculosum seed has yielded two novel daphnane diterpene esters, vesiculosin and isovesiculosin. Compounds 1 and 2 undergo rapid interconversion to an equilibrium mixture containing approximately 80% 1 and 20% 2 in solution at elevated temperatures. At 25 degrees or below, 1 and 2 may be isolated and stored for extended periods with minimal interconversion. Excoecariatoxin and simplexin are the major daphnane orthoesters present in D. vesiculosum, and 1 and 2 apparently are biosynthetic precursors of 3. Isolation of these compounds was monitored by bioassay against PS leukemia (in vivo), and structures were determined by 1H nmr, 13C nmr, ms, and comparison with known compounds.

Afghanistan↗

Cefotaxime and cephalosporins: adverse reactions in perspective.

Cefotaxime was used to treat infections in 2,579 patients during phase II and phase III clinical trials. This paper summarizes the adverse reactions reported to Hoechst-Roussel Pharmaceuticals (Somerville, NJ) during the treatment of these infections. Cefotaxime caused adverse reactions that are caused by all other cephalosporins, including pain at the site of injection (31.9%), thrombophlebitis (4.9%), skin rash (1.8%), thrombocytopenia (3.8%), glomerulotubular dysfunction (1.4%), diarrhea (1.2%), and superinfection (1.1%). Compared with cefazolin, cefotaxime caused pain on injection, phlebitis, and diarrhea more commonly (P less than 0.05) but caused superinfection less commonly (P less than 0.04). Since these data were obtained from many different sources by diverse methods, further controlled trials are needed to substantiate these differences. However, the adverse reactions caused by cefotaxime appear to be similar in spectrum and severity to those caused by other cephalosporins.

Bacterial Infections↗

Insert hearing protector effects.

The purposes of this investigation were two-fold: (1) to determine whether differences between measured ear canal diameter and actual earplug size affect sound pressure levels in the ear canal during exposure to high levels of noise; and (2) to determine if individuals would select the insert earplugs that conform to their measured ear canal diameter if the decision were left to them. The results indicate that: (1) very small differences between measured ear canal diameter and actual earplug size affect considerably the sound pressure levels in the ear canal during exposure to high levels of noise; (2) individuals typically select earplugs that are smaller than their measured ear canal dimensions when the decision is left to them; (3) the most skilled technician cannot always determine ear canal sizes due to limitations of available measuring instruments.

Adolescent↗

Heart rate response audiometry: bases, clinical techniques, and limitations.

Although a great deal of information is available concerning cardiovascular responsitivity to sensory stimuli, little is known regarding the pragmatic application of cardiac response measures to the problems of audiological assessment. Some relationships between arousal systems and cardiovascular function have begun to emerge, and the assessment of communicative behavior using HR response measures has become a more realistic goal, but the clinician who desires to utilize these techniques for audiological evaluation faces serious difficulties until further basic research has been conducted. Eisenberg (9) observed that instrumentation for measuring HR changes to auditory stimuli was research oriented and that measurement of HR data, although holding promise for the future, could not be realistically viewed as a clinical tool for audiological evaluation. Indeed, Eisenberg challenged audiologists to suspend the clinical application of these procedures until sufficient basic research evidence has accumulated to operationally define the problems at hand. Until that challenge is met, cardiotachometry will remain only a potentially rewarding procedure for assessment of the auditory system.

Acoustic Stimulation↗

Low cost ambulatory medical information system.

A simple, low-cost computerized minirecord system (minimal essential record) has been in operation at the Johns Hopkins Medical Clinic since mid-1975. The system has three primary components: (a) the Minirecord which contains a listing of problems and medications, plus information about visits to other clinics, (b) an appointment system used to organize materials prior to clinic encounters and assist in the follow-up of high risk special patients, and (c) an encounter data system to prepare reports used for management, quality assurance and training. This paper describes the system's operation, and reports on its utility and cost.

Computers↗

CT appearance of sacroiliac joint trauma in children.

Subchondral fractures in association with an intact joint space and narrowing of the joint space have not previously been reported with sacroiliac joint trauma in children. The subchondral fractures are thought to occur through the zones of cartilage proliferation and provisional calcification in the growing cartilage of the opposing sacroiliac joint surfaces and the zone of cambium layer of the periosteum in the areas of ligamental insertion, as these may represent structurally weak areas. This type of injury may explain the good long-term results in children with trauma to this region. Widening of the sacroiliac joint space in association with trauma as suggested on plain radiographs may thus not be as common as was previously thought.

Adolescent↗

Endovascular management of an aortobronchial fistula arising after resection of a primary aortic sarcoma: a case report.

The experience with the use of endovascular covered stents for aortic lesions has been growing. The early results of using endovascular covered stents for the exclusion of thoracic and infrarenal abdominal aortic aneurysms have been promising and are being investigated in multiple ongoing trials. Their usage for other aortic lesions has been reported sporadically, often as resourceful options in unusual and difficult clinical situations. The authors report a patient who had previously undergone resection of a thoracic aortic sarcoma and subsequently presented in extremis from an aortobronchial fistula. The evaluation and treatment of an aortic sarcoma and the successful urgent exclusion of an aortobronchial fistula through use of an endovascular covered stent are discussed.

Aorta, Thoracic↗

Endodermal sinus tumor of the nasopharynx and previous mature congenital teratoma.

Congenital teratoma of the nasopharynx is a rare tumor that has shown consistently benign behavior. In contrast, endodermal sinus tumor, even more unusual nasopharyngeal germ cell tumor, displays consistently aggressive behavior with most reports documenting early death of the patient. We report the clinicopathological features of a case of endodermal sinus tumor of the nasopharynx that developed in a 3-year-old girl who had a mature teratoma excised from the same site in the neonatal period. Local recurrence of the endodermal sinus tumor was followed by disseminated disease and death within 18 months.

Child, Preschool↗

Seroepidemiology of Bartonella vinsonii subsp. berkhoffii infection in California coyotes, 1994-1998.

The prevalence of antibodies to Bartonella vinsonii subsp. berkhoffii in coyotes (Canis latrans) in California ranged from 51% in central to 34% in southern and 7% in northern California. Seropositive coyotes were more likely to be from coastal than inland counties (p clustered distribution of Bartonella seropositivity in coyotes suggests that B. vinsonii subsp. berkhoffii infection is vectorborne. Further investigation is warranted to evaluate which arthropods are vectors and what the mode of transmission is from wildlife to domestic dogs and possibly humans.

Animals↗

Relation of HLA antibodies and graft atherosclerosis in human cardiac allograft recipients.

Although cyclosporine has helped make heart transplantation a clinical reality, long-term survival remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic heart transplants despite cyclosporine administration. The hypothesis of the present study is that cyclosporine-treated human heart transplant recipients are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 240 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with serum panel reactive antibody levels greater than 10% were considered antibody producers, whereas those with serum panel reactive antibody levels less than 10% were considered nonproducers. To establish the time course of post-transplantation sensitization, we have tested anti-HLA antibodies in sequential sera at 3-month intervals after transplantation. The 4-year actuarial survival rate of those patients whose panel reactive antibody levels were greater than 10% during the first 6 months after transplantation was 70%, whereas the survival rate of patients whose levels were less than 10% during this time was 93%. The results were significantly different (p less than 0.01). Further heterogeneity among the patients was demonstrated by differential analysis of survival in patients who showed (1) panel reactive antibody levels less than 10% in any of the sera obtained during the first year after transplantation, (2) panel reactive antibody levels greater than 10% in sera obtained during the first 6 months but not thereafter, and (3) panel reactive antibody levels greater than 10% throughout the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of electroporation pulse wave on the incorporation of viral RNA into tobacco protoplasts.

The uptake and expression of cucumber mosaic viral (CMV) RNA by tobacco protoplasts was examined using both square wave and exponential wave electroporation pulses. These electropulses, when supplied at sufficient field strength for a critical duration, enabled RNA to be incorporated and expressed in more than 60% of the surviving protoplasts. The results of experiments using these two electroporation wave forms showed significant differences in RNA uptake and expression. The number of viable protoplasts and cells showing expression of RNA was higher over a much broader range of experimental conditions using the square rather than exponential wave generator, even when both machines were optimized for maximal performance. However, at a narrow range of low field strengths the exponential wave pulse generated a higher percentage of transformants than did the square wave pulse. It was shown that after an electroporation pulse from either wave form, there were viable cells which expressed foreign RNA at predictable levels.

Biotechnology↗

Effect of simultaneous lung transplantation on heart transplant survival in rats.

Clinical observations in humans reveal that heart-lung transplant recipients suffer significantly less cardiac rejection than those receiving only heart transplants. A heterotopic combined heart-lung model in rats was used to test the hypothesis that the presence of the lung in this combination increases survival of the heart transplant. Cardiac survival was compared between en bloc heart-lung transplants and heart transplants. Low dosages of cyclosporine were used to prolong but not prevent the rejection process. Heart graft survival in the cyclosporine, 1 mg/kg/day, groups was significantly prolonged in heart-lung allografts. Histologic studies also demonstrated more advanced rejection of the heart in the heart-only transplant groups as compared with the heart-lung transplant groups. This study shows that the presence of the lungs in heart-lung allografts provides for prolongation of cardiac survival.

Animals↗

Present status of human cardiac allografts and prospects for xenografts.

Cardiac allotransplantation is no longer experimental. It is the standard by which all other methods of cardiac replacement must be judged. The dramatic improvement in survival and the quality of life of cardiac transplant recipients reflects many factors including refined criteria for patient and donor selection, as well as the clinical introduction of cyclosporine. Current contraindications to the procedure include: 1) age greater than 65 years, 2) active infection, 3) active malignant neoplastic disease, 4) recent pulmonary embolus or infarction, 5) irreversible renal or hepatic failure, and 6) fixed elevation of pulmonary vascular resistance. The introduction of cyclosporine has been accompanied by an increase in the 1 year survival. While the use of cyclosporine has not decreased the incidence of rejection episodes, it has dramatically decreased their severity. In addition, the incidence and severity of infectious complications, as well as the length of hospitalization, have been decreased with the introduction of cyclosporine. Despite the progress made, several problems remain in the management of transplant recipients. Chronic cyclosporine therapy has been associated with a disturbingly high incidence of hypertension and renal impairment, and a low, yet significant, incidence of malignant neoplasms. However, the most significant obstacle to successful clinical cardiac transplantation is the scarcity of donor organs. Many centers now report that the mortality rate for patients awaiting transplantation exceeds the mortality associated with the procedure itself. Donor scarcity has led to renewed interest in the development of mechanical cardiac devices and investigation into cross-species transplantation (xenotransplantation).

Bacterial Infections↗