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Biomedical subjects

E George

Publications and source records attributed to E George.

At least 91 records · Page 5Linked to original sources

Effects of azobenzene and aniline in the rodent bone marrow micronucleus test.

Azobenzene (AZB) is non-carcinogenic in mice, but a potent rat carcinogen, inducing tumours in the spleen and other abdominal organs. The present paper shows that AZB clearly induces micronuclei in the bone marrow of rats at a dose of 375 mg/kg and above. In mice, however, only a marginally positive response was seen at much higher doses, thus reflecting the species-specific carcinogenic effect of the compound. The clastogenic effect of a single dose of AZB was not detectable in the rat 24 h after dosing, but at the 48 h sampling time and later. However, when a multiple-dosing regimen was used, an accumulation of micronucleated polychromatic erythrocytes (PEs) was seen and the effect was detected 24 h after the last dose. Micronucleus induction in rats was paralleled by increased methaemoglobin levels followed by anaemia. This resulted in accelerated erythropoiesis, as indicated by both the increased percentage of PEs in bone marrow and the increased reticulocyte count in peripheral blood. In mice, anaemia and methaemoglobaemia were seen. However, there was no compensatory increase in the percentage of PEs or any consistent change in the reticulocyte count. Stimulation of erythropoiesis could therefore be a contributory factor in the micronucleus induction by AZB seen in rats. One of the major metabolites of AZB, aniline, was also found to cause micronucleus induction in rats. Aniline is also a rat-specific carcinogen. It may therefore be speculated that AZB acts as a carcinogen via the formation of aniline, which might then be metabolized in different ways in rats and mice.

Aniline Compounds↗

Two novel polyadenylation mutations leading to beta(+)-thalassemia.

In an ongoing effort to identify point mutations causing beta-thalassaemia, we have found two previously unreported mutations which are located in the Poly A site of the beta-globin gene. The screening programme used amplified DNA and dot-blot hybridization with several 32P-labelled oligonucleotide probes. DNA samples which remained unidentified by this methodology were subjected to sequencing with 32P-labelled primers and modified T7 DNA polymerase. The newly discovered mutations were confirmed by the dot-blot hybridization technique. One type concerned an AATAAA----AATGAA mutation in the polyadenylation site and was found in one family from Yugoslavia (including one patient with the C----T mutation at codon 29 in trans), one from Bulgaria (the patient had the G----A mutation at IVS-I-110 in trans), and one from Greece (this patient had the C----G mutation at IVS-II-745 in trans). Haematological data for three simple heterozygotes suggested a rather mild beta(+)-thalassemia. The second type involved an AATAAA----AATAGA mutation and was found in one family from Malaysia. The propositus had the beta E mutation on the other chromosome, was originally diagnosed as mild Hb E-beta(+)-thalassaemia, and had Hb A and Hb E percentages which were nearly the same.

Adult↗

Human atrial natriuretic factor (ANF). Characterisation of a monoclonal antibody panel and its use in radioimmunoassay.

The production of nine monoclonal antibodies to human atrial natriuretic factor (ANF 1-28) is described. All possible combinations of two antibodies failed to reveal any which could simultaneously bind ANF. Studies with ANF analogues and the antibodies having the three highest affinity values (KD = 5, 25 and 21 pM) indicated that the antibodies are directed to the central portion of the antigen molecule. The highest affinity antibody was able to replace polyclonal antisera in the radioimmunoassay of ANF in extracts of plasma.

Antibodies, Monoclonal↗

A systems approach to child abuse: management and treatment issues.

In the systems approach certain patterns of family interaction are seen as fitting with physical abuse towards children in the family. If these interactions are blocked or changed using specific family therapy interventions, the risk of further abuse will be significantly reduced. Identifying typical patterns of interaction that fit with abuse is a useful first step in planning the management of physically abusing families. A full systemic formulation of the presenting problem will address numerous systems and sub-systems simultaneously, notably the family-professional system, the family within the extended family/friendship system, and the nuclear family. Interventions may have to be directed on a variety of these levels. The Marlborough Family Service has assessed and treated over 100 child-abusing families. A family day unit is used as the setting, and a multifamily group as the principle medium of treatment. Within the day unit real life stress situations are recreated around everyday issues, enabling families to find new and nonviolent solutions to the problems of daily life. In the cases seen, approximately one-third have resulted in a recommendation of permanent alternative family care for the children. In those families reunited, the re-injury rate has been found to be extremely low.

Child↗

Genotoxicity of 1- and 2-nitropropane in the rat.

2-Nitropropane (2-NP) is a rat liver carcinogen, whilst the 1-isomer is non-carcinogenic in rodents. Although DNA repair tests in the rat liver discriminated clearly between the carcinogenic and the non-carcinogenic isomer, uniformly negative results have been published for the mouse bone marrow micronucleus test (BMMN test) with both isomers. Therefore, the latter assay did not discriminate between the carcinogenic and the non-carcinogenic isomer. To investigate whether this is due to endpoint specificity or organospecificity of 2-NP, studies were carried out in the rat in which micronucleus induction (bone marrow and liver) and unscheduled DNA synthesis (UDS) induction (liver) were measured after oral treatment with either nitropropane isomer. 2-NP induced UDS in the liver whilst the 1-isomer was negative, thus confirming the published studies. In the BMMN test, occasional small increases in the incidence of micronuclei were found for both compounds, but results were interpreted as negative after considering the control background data and the lack of reproducibility. By contrast, the liver micronucleus test revealed a clastogenic effect of 2-NP in the liver. This indicates that 2-NP induces chromosome aberrations as well as DNA repair in vivo, but it seems to act organospecifically. For 1-NP a slightly increased incidence of micronuclei was found in the liver, which was accompanied by a markedly increased mitotic index. It therefore remains questionable as to whether this increased micronucleus frequency for 1-NP is an indicator of a clastogenic effect, or whether it is caused by an increased cell proliferation induced by 1-NP. Consequently, it is too early to conclude whether the liver micronucleus assay is able to discriminate between the carcinogenic and non-carcinogenic isomer. However, the results provide further evidence that bone marrow assays are insufficient for the detection of all genotoxic carcinogens in vivo. This indicates the need for analysing a second tissue, particularly when negative bone marrow results have been obtained with in vitro genotoxins.

Alkanes↗

Malignant peripheral nerve sheath tumors of the skin.

We report two cases of cutaneous malignant peripheral nerve sheath tumors. One occurred in a patient without neurofibromatosis and manifested as a recurrent scalp nodule. Histologically, the lesion began as a benign-appearing, dermal neurofibroma and progressed to a highly cellular, pleomorphic neoplasm with prominent mitotic activity and invasion of the subcutis. Immunohistochemical and ultrastructural examination confirmed the nerve sheath origin of this tumor. The other case presented as a large scalp mass in a patient with an established diagnosis of neurofibromatosis; its immunohistochemical characteristics were identical to those of case 1. Although malignant peripheral nerve sheath tumors are uncommon in the skin, they can be effectively separated from other spindle cell neoplasms by specialized pathologic studies.

Female↗

Neuroendocrine differentiation in basal cell carcinoma. An immunohistochemical study.

Neuroendocrine differentiation in basal cell carcinoma (BCC) of the skin has been reported in the past on the basis of ultrastructural findings, argyrophilia, and the immunohistochemical detection of neuropeptides in such neoplasms. To assess further the relative frequency of neuroendocrine differentiation in BCC, paraffin sections of 53 randomly chosen cases were evaluated for Churukian-Schenk stain positivity and the expression of sensitive neuroendocrine markers. These included neuron-specific enolase (using a highly absorbed monospecific antiserum), chromogranin-A, synaptophysin, neurofilament protein, and Leu-7 antigen. Although 25% of cases demonstrated argyrophilia with the Churukian-Schenk method, suggesting a high frequency of possible neuroendocrine differentiation, immunohistochemical evidence of the same was observed in only two tumors (4%). These demonstrated immunoreactivity for chromogranin and neuron-specific enolase. The results of this analysis suggest that neuroendocrine differentiation in BCC is relatively uncommon, and that it is not reliably predicted by the results of argyrophil stains done on paraffin sections.

Antigens, Differentiation↗

Molecular characterization of beta-globin gene mutations in Malay patients with Hb E-beta-thalassaemia and thalassaemia major.

This study concerned the identification of the beta-thalassaemia mutations that were present in 27 Malay patients with Hb E-beta-thalassaemia and seven Malay patients with thalassaemia major who were from West Malaysia. Nearly 50% of all beta-thalassaemia chromosomes carried the G----C substitution at nucleotide 5 of IVS-I; the commonly occurring Chinese anomalies such as the frameshift at codons 41 and 42, the nonsense mutation A----T at codon 17, the A----G substitution at position -28 of the promoter region, and the C----T substitution at position 654 of the second intron, were rare or absent. Two new thalassaemia mutations were discovered. The first involves a frameshift at codon 35 (-C) that was found in two patients with Hb E-beta zero-thalassaemia and causes a beta zero-thalassaemia because a stop codon is present at codon 60. The second is an AAC----AGC mutation in codon 19 that was present on six chromosomes. This substitution results in the production of an abnormal beta chain (beta-Malay) that has an Asn----Ser substitution at position beta 19. Hb Malay is a 'Hb Knossos-like' beta +-thalassaemia abnormality; the A----G mutation at codon 19 likely creates an alternate splicing site between codons 17 and 18, reducing the efficiency of the normal donor splice site at IVS-I to about 60%.

Amino Acid Sequence↗

A molecular marker associated with mild hemoglobin H disease.

The clinical spectrum of HbH disease varies from a benign disorder to a severe anemia which is blood-transfusion dependent. Heterogeneity at the clinical level is now being understood in terms of the underlying molecular defects. In this study a mild phenotype found in a group of patients with HbH disease is associated with two types of alpha-thalassemia. These are: alpha+-thalassemia (-alpha 3.7/) and alpha 0-thalassemia (--SEA/). In contrast, a second group with more severe HbH disease has a non-deletional alpha-thalassemia defect instead of alpha+-thalassemia (genotype alpha alpha T/--SEA). In the majority of cases, the basis for non-deletional alpha-thalassemia is Hb Constant Spring.

Adolescent↗

Homozygous haemoglobin E in association with hereditary ovalocytosis.

Hereditary stomatocytic ovalocytosis and haemoglobin E are two genes present in 3-5% of Malays. This is a report of a 22 year old Malay college student with homozygous haemoglobin E and hereditary stomatocytic ovalocytosis where the clinical effects seen were the result of the summation of these genes: he was asymptomatic, presenting with moderate jaundice, moderate hepatosplenomegaly, and a mild haemolytic anaemia.

Adolescent↗

Principles of cancer pain management. Use of long-acting oral morphine.

Oral morphine is increasingly recognized as the pharmacologic standard for cancer pain management. Yet for the primary care physician and oncologist alike, misconceptions of the safety and efficacy of oral morphine along with lack of recognized guidelines for use have often resulted in inadequate cancer pain therapy. Use of controlled-release oral morphine sulfate (MSC) requires additional guidelines for optimum analgesia. Proposed are ten principles of dosing oral morphine, especially MSC, which were followed in a clinical trial involving cancer patients. MSC dosed at 8-, 10-, and 12-hour intervals was compared with immediate-release morphine (IRMS) dosed every four hours, and with prestudy analgesics. Patients achieved satisfactory analgesia at daily doses (mean +/- SE) of 118.0 +/- 8.6 mg and 111.4 +/- 12.6 mg (P greater than .05) for IRMS and MSC, respectively. Dosing endpoints were determined by titration with IRMS and MSC to a minimal and equivalent amount of supplemental short-acting analgesic. Side effects were typical for opioids and tolerated except for one dropout on IRMS (nausea and constipation). The ten principles have been incorporated into a dosing scheme as a practical guide for MSC therapy.

Administration, Oral↗

Nursing considerations for the patient with a total artificial heart.

At our institution, the TAH has been identified as a valuable support to a select subgroup of individuals with end-stage heart disease as a bridge to transplantation. Length of implantation has varied from 1 to 48 days in the PUH series. Management of the care of the TAH-implanted patient requires a collaborative effort by nurses, physicians, and biomedical engineers. Nurses caring for the patient must have extensive knowledge of postoperative care of the high-risk cardiac surgical patient that is supplemented by the specialized knowledge of TAH function and monitoring. We have identified specialized components to the nursing care of the patient following TAH implantation. Monitoring for hemorrhage is important in the immediate postoperative period; anticoagulation and assessment of possible embolic events are later considerations. Knowledge of the relationship between TAH function and changing preload and afterload enhances the nurses' interpretation of COMDU and hemodynamic monitoring parameters, and is essential when applied to other nursing interventions, such as patient positioning and mobilization. Nursing-care measures to prevent atelectasis or consolidation are essential to prevention of pneumonia. Prevention of infection is crucial to facilitate transplantation. Practice of aseptic technique with particular care to drive-line insertion sites is necessary. Pain management, as well as nutritional and psychologic support, are important to promote patient well-being (a nursing-care plan is outlined in Table 1). The goals of all nursing-care measures are an improved perfusion state as offered by the TAH, prevention of possible complications associated with TAH implantation, and prevention of possible complications of critical illness and immobility. The desired outcome is a patient with a stabilized or improving condition prior to cardiac transplantation. It has been exciting to participate in the development of nursing-care guidelines for a patient population that has little precedent. The TAH creates a symbiotic relationship between man and machine, and nursing-care responsibilities have grown to encompass the mechanical aspects of this relationship. Satisfaction has increased as well, as the nurse is able to provide a specialized service in the provision of a life-saving therapy and be a vital element in the successful implementation of an artificial-heart program. As advances are made in the development of mechanical devices that assist or replace the human heart, ongoing evaluation and refinement of nursing care guidelines are essential.

Assisted Circulation↗

Cervical encerclage--a stitch in time: analysis of 23 cases.

Cervical incompetency has been recognized as a cause of repeated reproductive loss. Currently many surgeons cast doubt on the existence of cervical insufficiency and the efficiency of encerclage to salvage the situation. Over a period of 3 years we did cervical encerclage for 23 patients with recurrent pregnancy loss in whom all other causes were ruled out. Twenty-one patients benefitted by the procedure, only one ended in missed abortion and one patient had preterm delivery with early neonatal loss. We had a fetal salvage of 91.3%. Birth weights of the babies were above 2500 g in 65.2%. In our experience, with proper selection, patients benefitted from encerclage performed at the appropriate time.

Abortion, Habitual↗