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Biomedical subjects

R Harrell

Publications and source records attributed to R Harrell.

14 recordsLinked to original sources

Human amnion collagen for soft tissue augmentation--biochemical characterizations and animal observations.

As bovine collagen is currently being scrutinized as to its immunogenicity in clinical use, a human source collagen, human amnion collagen (HAC), has been developed in our laboratory as an injectable biomaterial for soft tissue augmentation. Pepsin-extracted human amnion collagen was highly purified and reconstituted. Gamma irradiation was employed to ensure complete sterility and to produce cross-linking in collagen chains to improve implant persistence without the use of chemical additives. The purity and characteristics of human amnion collagen were proven by amino acid assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immune blotting, and collagenase digestion. Animal studies comparing both irradiated and nonirradiated amnion collagen to bovine collagen (Zyderm and Zyplast) were carried out in a rat model. Humoral immunity was evaluated by examining the sera for antibody reactivity towards the implanted human collagen by the ELISA test. Insignificant antibody levels against human amnion collagen were found. Animal observation revealed fibroplasia, vascular infiltration, and the development of adipocytes with the implant as well as a lack of inflammatory response following up to 12 months of implantation. The persistence rate of our human amnion collagen was equal to, or even longer than, that of both types of bovine collagen implants.

Amino Acids↗

Functional communication training with and without extinction and punishment.

Functional communication training has been reported to be a promising treatment for severe behavior problems. In this study, functional communication training alone and combined with extinction and/or punishment was evaluated for 4 clients with severe retardation, behavior problems, and communication deficits. The participants were inpatients on a hospital unit for treatment of severe behavior disorders. They received individualized interventions based on functional assessment that included reinforcement of a communication response with the same function as their destructive behavior. Results showed that for some patients, functional communication training was not sufficient to produce clinically significant reductions in destructive behavior, and the combination of training plus punishment produced the largest and most consistent reductions.

Adult↗

Enhancement of radiation-induced cell killing and DNA double-strand breaks in a human tumor cell line using nanomolar concentrations of aclacinomycin A.

Several agents that induce differentiation have previously been shown to induce the terminal differentiation of leukemic cells and enhance the radiosensitivity of certain solid tumor cell lines in vitro using millimolar concentrations. We now report that aclacinomycin A (ACM), a potent inducer of leukemic cell differentiation in vitro, can significantly enhance the radiosensitivity of a human colon tumor cell line (Clone A) at a concentration of 10 nM. Based on colony-forming efficiency, the maximum increase in radiosensitivity was found using 15 nM ACM for 3 days with a dose enhancement factor of 1.4 at a surviving fraction of 0.10. This treatment increased cell doubling time, but had no effect on cell-cycle phase distribution. To gain insight into the mechanisms responsible for this radiosensitization, gamma-ray-induced DNA single- and double-strand breaks were examined. Aclacinomycin A had no effect on the induction of DNA single-strand breaks but significantly enhanced the formation of gamma-ray-induced DNA double-strand breaks. The rate or extent of repair of the induced double-strand breaks was not influenced by ACM treatment. These data suggest that ACM, at achievable plasma concentrations, can enhance the radiosensitivity of a human tumor cell line by increasing the initial level of radiation-induced DNA double-strand breaks.

Aclarubicin↗

Computed tomography for evaluation of puerperal infections.

Pelvic computed tomography was used to evaluate 74 women with persistent puerperal infection. There was at least one abnormal roentgenographic finding in 57, and these are correlated with clinical and surgical findings. In 16 women, a palpable pelvic mass was seen on tomography, however, masses not appreciated clinically were visualized in another 29 women, and in five, a clinically palpable mass was not visualized by tomography. In 12 women who had a normal pelvic examination, septic pelvic thrombophlebitis was diagnosed by tomography. Over-all, there was poor correlation with roentgenographic findings and uterine incisional necrosis and dehiscence. We conclude that pelvic tomography is useful to evaluate some women with persistent puerperal infection, but that these studies must be correlated with clinical findings.

Adolescent↗

The growth of human fibroblasts and A431 epidermoid carcinoma cells on gamma-irradiated human amnion collagen substrata.

Human fibroblasts and A431 human epidermoid carcinoma cells were cultured on gamma-irradiated human amnion collagen as well as on plastic dishes and non-irradiated collagen coated dishes. The morphology, attachment, growth and short-term cytotoxicity of these culture conditions have been determined. Both irradiated and non-irradiated amnion collagen enhanced the attachment and proliferation of fibroblasts as compared to the plastic dishes. No differences in these properties were observed for A431 cells cultured on irradiated collagen when compared with culture on non-irradiated collagen substrates. Cytotoxicity assays showed that irradiated and non-irradiated collagens were not cytotoxic for either fibroblasts or A431 cells. The results demonstrated that amnion collagen irradiated at doses of 0.25-2.0 Mrads is optimal for cell growth.

Amnion↗

The effect of gamma irradiation on injectable human amnion collagen.

The effect of gamma irradiation on the physicochemical properties of injectable human amnion collagen was investigated. Pepsin-extracted human amnion collagen was purified, reconstituted, and irradiated with varying doses of gamma irradiation (0.25 Mrads to 2.5 Mrads). Gamma irradiation had a significant impact on the physical characteristics of the collagen. The neutral solubility of collagen in PBS at 45 degrees C was decreased from 100% for the nonirradiated control sample to 16% for the 2.5 Mrads irradiated sample. SDS polyacrylamide gel electrophoresis also demonstrated the dose-dependent effect of gamma irradiation on collagen cross-links. Electron microscopic observation revealed that even at low irradiation dose (0.25 Mrads), collagen fibril diameter increased. The average diameter was 50 nm for nonirradiated control fibrils, while 4.4 percent of the irradiated collagen fibrils had a diameter greater than 100 nm. Irradiated collagen showed little evidence of damage. Well-preserved cross-striations were found in collagen fibrils at all doses of irradiation. Native amnion collagen irradiated with gamma rays demonstrated a slight increase in resistance to collagenase degradation compared with nonirradiated native collagen samples. Increased resistance to collagenase did not correlate with increasing irradiation dose. After 30 min of incubation at 37 degrees C, both irradiated and nonirradiated collagen was completely digested by collagenase. However, gamma-irradiated collagen did become more sensitive to hydrolysis by trypsin. The higher the irradiation doses used, the greater sensitivity to trypsin was observed. At 0.25 Mrads irradiation only a slight increase was found. No marked differences in amino acid composition were noted among the high dose irradiated, low dose irradiated and control amnion collagen.

Amino Acids↗

Immune response to gamma-irradiated injectable human amnion and human skin collagens in the rat.

The immune response in rats to gamma-irradiated human amnion and human skin collagen was characterized through histologic and immunologic methods. Pepsin-extracted human amnion collagen and skin collagen were purified and reconstituted. Implants of amnion collagen demonstrated greater persistence than skin collagen. For amnion collagen implants, no significant inflammatory response was found. Fibroblast and adipocyte ingrowth and neovascularization were present. Conversely, obvious inflammatory infiltration was evident in the skin collagen implants. Enzyme-linked immunosorbent assay results showed that anti-amnion collagen antibody levels were significantly lower than anti-skin collagen antibody levels against their respective implant materials. The ratios of type I to type III collagen are 56:44 and 95:5 for amnion collagen and skin collagen, respectively. These findings suggest that in this heterologous type system, type III collagen-rich amnion collagen preparations appear superior to skin collagen for soft-tissue augmentation.

Amnion↗

Noninvasive localization of parathyroid adenomas: a comparison of X-ray computerized tomography, ultrasound, scintigraphy and MRI.

Thirty-two (32) patients with primary hyperparathyroidism (17 with prior localization surgery, 15 without) were studied by a combination of computed tomography (CT), ultrasound (US), nuclear medicine (NM), and magnetic resonance imaging (MRI) for parathyroid adenoma localization. The sensitivity and true-positive ratio of each imaging technique and various combinations of techniques were evaluated. Of the 28 proven parathyroid adenomas (27 by surgery, 1 by digital subtraction angiography), 24 were imaged by two techniques, 19 by three techniques, and 10 by all four imaging techniques. The sensitivities were NM (65%), CT (76%), US (77%), and MRI (81%). The differences between true-positive ratios of 82%, 64%, 71%, and 77%, respectively, were not statistically significant. If multiple techniques were considered as a single test (i.e., a positive localization requires two or more tests to be positive at the same location), then sensitivity for a two-study combination was 79% and true-positive ratio 86%. Three techniques showed a sensitivity of 63% and a true-positive ratio of 92%, four modalities 40% and 100%, respectively. There was no significant difference in the various combinations of techniques employed (e.g., CT and US, US and MR, NM and MR, etc.). Thus, there appears to be an advantage in performing multiple techniques (regardless of which combination is selected) until two tests are positive at the same location.

Adenoma↗

Diagnosing depression in the medically ill: validity of a lay-administered structured diagnostic interview.

Understanding the validity of structured psychiatric diagnostic interviews in medically ill patients will advance the ability to conduct research into the treatment and management of these disorders in general medical settings. We compared the University of Michigan version of the CIDI (Composite International Diagnostic Interview) for major depression to a clinical gold standard, derived through Spitzer's Longitudinal, Expert, All Data (LEAD) criteria based on the SCID-III-R. A convenience sample of medical inpatients was administered the SCID-III-R and the CIDI for major depression in random order. A physician panel reviewed the SCID interview and other pertinent data and determined whether patients had a lifetime or current (past month) diagnosis of major depression. The CIDI was scored with and without hierarchical exclusions for mania, hypomania, substance use, or medical illness. When the UM-CIDI was scored for a lifetime diagnosis of major depression without hierarchical exclusions, agreement above chance (kappa) was very good (kappa = 0.67) between the CIDI and the physician panel and good (kappa = 0.46) when the UM-CIDI was scored with exclusions. Agreement above chance for diagnosis of a recent disorder was better for UM-CIDI scoring with exclusions (kappa = 0.51) compared to scoring without exclusions (kappa = 0.43). Predictive value-positive was excellent in both scoring versions for a lifetime diagnosis (82%) and good to very good for current depression (46% and 62%). In all cases predictive value-negative was very good to excellent (77-93%). Discordant cases were almost uniformly due to difficulties in attribution of symptoms to medical illnesses. We conclude that the CIDI can perform acceptably as a research instrument to diagnose major depression in medically ill patients, potentially supplemented by clinician review of cases identified by the CIDI with current disorder.

Adult↗

The effects of family history, sobriety length, and drinking history in younger alcoholics on P300 auditory-evoked potentials.

Event-related potentials (ERPs) have been shown to be different between alcoholics and non-alcoholics. Of particular interest to investigators has been the P300 wave. Because it has been shown that alcohol-induced neural damage can alter P300 waves, particularly amplitude, we attempted to examine alcoholics who most likely suffered little damage because they drank heavily for relatively few years (mean = 6.9 years). The effects of long-term sobriety (mean = 5.0) were also investigated to determine if cognitive functioning, as measured by auditory-evoked P300 waves, varies with increased abstinence. Because family history for alcoholism has also been shown to influence P300 amplitude and latency, alcoholics and controls with and without family history were examined. The alcoholic group had significantly longer latencies in P300 measures in both the family history positive and negative groups; P300 amplitudes between alcoholics and non-alcoholics did not vary, regardless of family history. P300 waves were unaffected by sobriety length or drinking history. The results support the hypothesis that P300 differences can be seen between alcoholics and those at risk for alcoholism.

Adult↗