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Biomedical subjects

C Richards

Publications and source records attributed to C Richards.

At least 91 records · Page 5Linked to original sources

Cutaneous toxicity associated with high-dose cytosine arabinoside.

High-dose cytosine arabinoside (HDAC) is used to treat adults with acute and chronic leukemia and non-Hodgkin's lymphoma. Although HDAC is associated with various toxicities, cutaneous toxicity in particular leads to alterations in comfort, interference with daily living activities, and increased risk of infection. The incidence of cutaneous toxicity ranges from 3%-72%. A review of the literature revealed a variety of terms describing this toxicity, which begins as erythema and progresses to painful swelling, bullae formation, and desquamation. The etiology is unclear, and the severity is related to the number of consecutive doses. Interventions specific to prevention and treatment of this toxicity were found to be minimal, with no interventions scientifically examined. The challenge for nurses is to explore measures that will minimize the complications, treat the manifestations, and document the impact of these problems on quality of life.

Clinical Trials as Topic↗

Synoviocyte derived granulocyte macrophage colony stimulating factor mediates the survival of human lymphocytes.

Synoviocytes have been shown to be effector cells capable of synthesizing and secreting a variety of cytokines and growth factors. We demonstrate here that synoviocyte derived conditioned medium has immunoregulatory properties as it enhances human peripheral blood lymphocyte survival in a dose dependent manner in vitro. The effect elicited by synoviocyte derived conditioned medium from patients with rheumatoid arthritis (RA) was greater than that induced by synoviocyte derived conditioned medium from patients with osteoarthritis. Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in synoviocyte derived conditioned medium with significantly higher levels present in synoviocyte derived conditioned medium from patients with RA. Recombinant human GM-CSF induced survival of human lymphocytes in vitro and a monoclonal antibody to human GM-CSF fully abrogated synoviocyte derived conditioned medium induced survival. Our results demonstrate that synoviocyte derived GM-CSF may be important in the retention of lymphocytes, which is a central pathological characteristic of the rheumatoid joint.

Arthritis, Rheumatoid↗

Prevalence of antibody to hepatitis C virus in a blood donor population.

Blood samples from 2000 accepted blood donors and 343 deferred donors with antibody to hepatitis B core antigen (anti-HBc) and/or an alanine aminotransferase (ALT) elevation were evaluated for antibody to hepatitis C virus (anti-HCV). Sixteen (0.8%) of the 2000 sera initially reacted on enzyme-linked immunosorbent assay (ELISA); 12 (0.6%) were repeatably reactive. One repeatably reactive sample had an elevated ALT; two reacted on anti-HBc testing and had ALT elevations. When the repeatably reactive ELISA samples were tested by an immunoblot assay, four reacted, three were indeterminate, and five did not react. Among the 343 deferred donors, HCV antibodies were detected in 8 (3.8%) of 210 anti-HBc-reactive samples, 12 (11.8%) of 104 elevated-ALT samples, and 15 (52%) of 29 combined elevated-ALT and anti-HBc-reactive samples; 25 of 28 reacted on immunoblot. The anti-HBc-reactive sera were subdivided into groups according to strength of anti-HBc reactivity (weak or strong) and antibody to hepatitis B surface antigen status and then were compared for anti-HCV reactivity rates. The group of samples showing the greatest frequency of anti-HCV had strong anti-HBc reactivity. For blood donors, the anti-HCV test correlates with the surrogate tests for non-A, non-B hepatitis (anti-HBc and ALT); however, most anti-HCV-reactive units remain undetected by surrogate tests, so that implementation of anti-HCV screening should further reduce the transmission of HCV via transfusion.

Alanine Transaminase↗

Use of endotoxin retentive intravenous filters with paediatric total parenteral nutrition solutions.

We studied the retention of endotoxin released in a clinically relevant form by senescent bacteria during filtration of amino acid-based total parenteral nutrition (TPN) solutions by the PALL Intravenous Set Saver Filter (ELD96). The ELD96 was shown to be capable of providing an effluent free of detectable endotoxin (less than 0.125 endotoxin unit-equivalents/ml) when challenged with 10(6) total cells of Pseudomonas aeruginosa during simulated clinical TPN infusion. Parallel control experiments showed that endotoxin was released from the test organism and penetrated through conventional intravenous (i.v.) solution filters.

Cellulose↗

Depressive disorders in childhood. IV. A longitudinal study of comorbidity with and risk for anxiety disorders.

As part of a longitudinal nosologic study of major depressive disorder (MDD), dysthymic disorder (DD), and adjustment disorder with depressed mood (ADDM) in a school-age cohort, we examined the prevalence and clinical consequences of comorbid anxiety disorders. We also estimated the risk of a first anxiety disorder and examined its predictors. Of 104 cases, 41% had anxiety disorders in conjunction with their index depression, which was more likely with MDD and DD than with ADDM. The age-corrected risk of a first anxiety disorder was 0.47 up to age 18 years. Separation-anxiety disorder was the most frequent diagnosis of anxiety, followed by overanxious disorder of childhood. Among the MDD cases with comorbidity, the anxiety disorder preceded the depression about two thirds of the time and often persisted after the depression remitted. The effect of comorbid anxiety disorder on the length of index MDD depended on the presence of other clinical features, but it did not seem to affect the risk of subsequent MDD or the course of DD or ADDM. Concurrent maternal psychopathology and poor physical health increased the risk of anxiety disorder in the children, but a history of prior separation from parental figures did not seem to have an effect.

Adjustment Disorders↗

Diagnosis of acute appendicitis in pregnancy.

Although the clinical diagnosis of appendicitis in pregnancy seems to be complicated by the physiologic changes of pregnancy, evidence from controlled studies is lacking. The aims of this study were to determine whether there are any features of appendicitis in pregnant women that would help to establish the diagnosis and whether any difference exists between the presentation of appendicitis in pregnant and nonpregnant women. Twenty-eight pregnant women with a clinical diagnosis of appendicitis were compared with an equal number of nonpregnant patients matched for age and randomly selected from a group of patients who had appendicitis. No differences were observed in the presenting symptoms, physical signs and laboratory tests. The false-positive rates were identical. The results indicated that the diagnosis of appendicitis is no more difficult in the pregnant state than in the nonpregnant state.

Abortion, Spontaneous↗

Characterization of plasmid pAZ1 and the type III dihydrofolate reductase gene.

The plasmid pAZ1, which determines trimethoprim and sulfonamide resistance, was characterized by restriction endonuclease mapping. The restriction map was identical to that of the incQ plasmid RSF1010 over a 5.1-kbp region. The type III dihydrofolate reductase gene was cloned, and the DNA sequence was determined. The predicted protein had 162 amino acid residues, and it was more closely related to the gram-negative bacterial chromosomal dihydrofolate reductases than to other plasmid or vertebrate dihydrofolate reductases. Sequence identity was 51% with the Escherichia coli enzyme and 44% with the Neisseria gonorrhoeae enzyme.

Amino Acid Sequence↗

Fertilization of human oocytes by sperm from infertile males after zona pellucida drilling.

Infertile couples who had failed to achieve fertilization of oocytes in previous trials of in vitro fertilization (IVF) were treated by IVF with zona pellucida drilling. Zona drilling entails use of micromanipulation to introduce a gap in the zona pellucida either mechanically or by localized application of a zona solvent from a microneedle. Ten couples were treated, from whom 63 oocytes were recovered for manipulation. Sixteen eggs were denuded of the cumulus oophorus only, and the remaining 47 eggs were subjected to zona drilling. Of the 16 eggs denuded but not drilled, 4 (25%) were fertilized. Of the 47 oocytes drilled, 31 survived (67%) and 10 of the surviving eggs (32%) were fertilized. The polyspermy rate for drilled eggs that fertilized was high (5/10, 50%), and polyspermic eggs were often penetrated by more than two spermatozoa. The remaining five eggs fertilized after drilling were diploid fertilizations, and in three cases cleavage was followed by embryo transfer, although pregnancies were not obtained. These data indicate that zona drilling has the potential for establishing pregnancies in instances where treatment by standard IVF would fail. In addition, results indicate that the block to polyspermy in human eggs occurs at the level of the zona pellucida.

Female↗

Spontaneous in vitro release of alveolar-macrophage cytokines after the intratracheal instillation of bleomycin in rats. Characterization and kinetic studies.

The intratracheal administration of bleomycin in rats elicits an acute inflammatory response in the lung followed by the development of pulmonary fibrosis. The alveolar macrophage (AM) is a key effector cell involved in this process because of its potential to release a variety of hormonelike molecules (cytokines) that can modulate systemic responses as well as the local response of other lung cells including the interstitial fibroblast. In this report, we have documented the chronology of the in vitro spontaneous release of AM cytokines after a single instillation of bleomycin. We show that supernatants from AM harvested after the administration of bleomycin but not after saline contain lymphocyte-activating factor (interleukin-1) activity. Maximal activity was detected between 6 and 12 h and was barely detectable by Day 7 after bleomycin. In addition, supernatants showing interleukin-1 (IL-1) activity also inhibited the proliferation of log-phase normal rat lung fibroblasts. Fractionation of supernatants from AM harvested 6 h after bleomycin demonstrated that both lymphocyte-activating factor and fibroblast modulatory activity coelute in the same 18-kDa region, suggesting that IL-1 may demonstrate both activities. We also report here the spontaneous release of a second AM cytokine, hepatocyte-stimulating factor, which we have recently shown in humans to be identical to interferon beta 2 and which initiates the hepatic acute-phase protein response. The release of this 30-kDa cytokine from AM of rats exposed to bleomycin has a different chronology than does IL-1, showing a steady increase over time, with maximal activity at Day 28 after bleomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells.

Human hepatoma (HepG2) cells respond to unfractionated conditioned media of human squamous carcinoma (COLO-16) cells and lipopolysaccharide-stimulated human peripheral blood monocytes by increasing the synthesis of alpha 1-acid glycoprotein, haptoglobin, complement C3, alpha 1-antichymotrypsin, alpha 1-antitrypsin, and fibrinogen, while decreasing the synthesis of albumin. The regulation of the acute phase proteins is mediated by hepatocyte-stimulating factors (HSF) and interleukin 1 (IL-1) present in the conditioned medium. Purified HSF-I from COLO-16 cells stimulates preferentially alpha 1-acid glycoprotein synthesis, whereas COLO-HSF-II stimulates preferentially the synthesis of haptoglobin, fibrinogen, and alpha 1-antitrypsin. HSF from monocytes, which has been identified as interferon-beta 2 (B cell stimulating factor-2), displayed the same activity as COLO-HSF-II. Dexamethasone alone had no effect on acute phase plasma protein synthesis but enhanced the response to various HSF severalfold. IL-1 had a relatively low stimulatory activity on the synthesis of alpha 1-acid glycoprotein, haptoglobin, and alpha 1-antichymotrypsin but strongly reduced the basal expression of fibrinogen. The only synergistic action between IL-1 and HSF (or interferon-beta 2) was noted for the synthesis of alpha 1-acid glycoprotein. Tumor necrosis factor active on other hepatic cells failed to modulate significantly the expression of any plasma proteins in HepG2 cells. These studies showed that for an optimal HepG2-cell response a combination of HSF (or interferon-beta 2), IL-1, and dexamethasone is needed. This finding might indicate the identity of some of those hormones involved in regulation of the hepatic acute phase response in vivo.

Acute-Phase Proteins↗