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Biomedical subjects

G King

Publications and source records attributed to G King.

At least 19 recordsLinked to original sources

Integration of a barcode reader with a commercial flow cytometer.

This report describes the application and installation of a barcode reader on a standard EPICS Elite flow cytometer. The barcode reader system eliminates keyboard entry of sample information on the cytometer. The system automates the transfer of sample information already present in our laboratory database to the cytometer at run time. The system uses a standard "off-the-shelf" bar code wand with a personal computer keyboard interface and requires no additional software at run time. No typing of sample information is required by the operator at any stage of normal sample operation at the cytometer. All operations are automatically coded into the cytometry software using the macro functions of the software. Tubes are inserted into the tube reader and sample information is transferred automatically into the cytometer. We have found that the system allows rapid and continuous operation of routine clinical and research samples. This automated data entry also reduces the possibility of data input errors.

Electronic Data Processing

Immunopathological changes in the skin following recombinant interleukin-2 treatment.

The systemic administration of the cytokine recombinant interleukin-2 (rIL-2) is associated with a number of toxic effects, including dermatological complications. The clinical, histological, and immunopathological changes occurring in the skin of six patients receiving rIL-2 for metastatic colorectal carcinoma have been studied. All of the patients developed a diffuse erythema shortly after initiation of the treatment. In one patient, generalized erythroderma and photosensitivity developed. The initial biopsy revealed patchy spongiosis, focal exocytosis, and focal basal layer damage with a perivascular chronic inflammatory cell infiltrate. With further treatment there was progressive thickening of the epidermis. Immunohistochemistry revealed changes in the expression of CD1, CD3, CD4, and CD25, particularly on perivascular cells. Additionally, there was an increase in the expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes in the basal and mid-layers of the epidermis, endothelial cells, and perivascular cells. It is hypothesized that the expression of ICAM-1 by the epidermal keratinocytes may be the important event in initiating the cutaneous manifestations associated with rIL-2 administration.

Aged

Echocardiographic abnormalities in ankylosing spondylitis.

Twenty four patients with ankylosing spondylitis of 10 or more years' duration were assessed for evidence of cardiac disease. Seven patients (29%) had evidence of cardiac disease, including one patient with a pericardial effusion, three with conduction abnormalities, and two with aortic incompetence. Aortic incompetence in one patient was clinically silent and was detected only with Doppler echocardiography. This patient had, in addition, thickening of the posterior aortic wall, an echocardiographic feature not previously described in ankylosing spondylitis. There was no evidence of aortic valve disease in a control group matched for age and sex. Patients with ankylosing spondylitis and cardiac abnormalities were older, had a longer disease duration, and more peripheral joint disease than those without cardiac abnormalities. Doppler echocardiography is a useful technique in the assessment of cardiac disease in ankylosing spondylitis and may detect aortic valve disease at an early preclinical stage.

Adult

Expression of c-erbB-2 oncoprotein in salivary gland tumours: an immunohistochemical study.

Sections of formalin-fixed, paraffin-embedded primary salivary gland tumours were stained with a monoclonal antibody to the c-erbB-2 oncoprotein to determine the incidence and significance of expression of this protein. The series of 131 tumours comprised 33 cases of pleomorphic adenoma, 2 of malignant mixed tumour, 1 oxyphil adenoma, 31 Warthin's tumours, 4 basal cell adenomas, 6 mucoepidermoid carcinomas, 14 acinic cell carcinomas, 19 adenoid cystic carcinomas, 3 squamous carcinomas, and 18 poorly differentiated adenocarcinomas. Positive staining, as defined in previous studies, was present in five tumours (three cases of poorly differentiated adenocarcinoma, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma). A review of the medical records of all patients did not disclose any clear difference between the clinical behaviour of positive and negative cases over a period of follow-up that ranged from 18 to 120 months. The findings of this study indicate that the protein product of the c-erbB-2 proto-oncogene is infrequently expressed in salivary gland tumours, and when it is localized on the tumour cell surface membrane, there is no clear evidence that this determines the biological behaviour of the tumour.

Biomarkers, Tumor

Efficacy of acemannan in treatment of canine and feline spontaneous neoplasms.

Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.

Adjuvants, Immunologic

Urinary excretion of metabolites of norepinephrine in Tourette's syndrome.

Urinary excretion of the norepinephrine metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NMR) was measured in Tourette's Syndrome (TS) patients and in control subjects matched for age and education. The 24-h excretion (expressed per gram of creatinine) of total MHPG and of free and total (free + conjugated) NME was significantly lower in TS patients than in the normal subjects.

Child

Indirect retainers in soft palate obturator design.

Definitive framework design for the maxillofacial patient with complete maxillary dentition who has had a soft palate resection requires the use of direct and indirect retainers. It is possible to retain these prostheses, however, with only two posterior clasps and indirect retainers without clasps. This design offers an esthetic, retentive, and functional restoration while preserving existing structures. Four clinical applications are described.

Denture Design

Plasma amino acids in attention deficit disorder.

This study examines plasma amino acids in a group of 28 patients meeting DSM-III criteria for attention deficit disorder (ADD) and 20 control subjects. Compared with controls, the ADD subjects had significantly lower levels of phenylalanine, tyrosine, tryptophan, histidine, and isoleucine. These data suggest a general deficit in amino acid transport, absorption, or both.

Amino Acids

Phenylethylamine metabolism in Tourette's syndrome.

Beta-phenylethylamine, phenylalanine, and phenylacetic acid were examined in 24-hour urine samples and/or plasma samples obtained from 28 medication-free patients with Tourette's syndrome and 20 control subjects matched for age and education. Statistical analyses revealed that Tourette patients had lower plasma phenylalanine and urinary free beta-phenylethylamine compared with the controls, but did not differ on urinary total levels of phenylacetic acid. Fifty percent of the Tourette patients had a urinary beta-phenylethylamine level that was lower than the lowest control subject. In addition, urinary beta-phenylethylamine levels were inversely related to several scores from the Tourette Syndrome Global Scale. These data suggest that abnormalities in synthesis or metabolism of beta-phenylethylamine may be involved in the etiology of some patients with Tourette's syndrome.

Child

Acute endotoxin-induced lymphocyte subset sequestration in sheep lungs.

Endotoxemia is associated with an early phase of pulmonary hypertension and a later increase in microvascular permeability. These physiologic changes are attended by peripheral blood and lung lymph leukopenia and a rapid accumulation of both granulocytes and lymphocytes in the peripheral lung. In the present study, the numbers of lymphocytes in blood, lung lymph, and lung tissue after infusion of endotoxin were determined by fluorescent labeling of lymphocyte populations with monoclonal antibodies to sheep T1, T4, T8, or leukocyte common antigen and with rabbit anti-sheep immunoglobulins (B cells). Peripheral blood, lung lymph, and lung tissue samples were collected at baseline and 15, 30, 60, 120, 180, and 240 minutes after the start of intravenous infusion of E. coli endotoxin (1.25 micrograms/kg, N = 6) or saline (N = 4) from open-chest anesthetized sheep. Pulmonary artery pressure and lung lymph flow were also monitored at these times. Endotoxin caused marked reductions in the number of T and B lymphocytes in blood and lung lymph. As compared with baseline, total blood leukocytes and granulocytes were significantly reduced below control levels from 30 minutes of endotoxin, and lymphocyte numbers were reduced from 60 minutes. T1, T4, T8 and B lymphocyte subsets contributed to the fall in blood lymphocytes. Endotoxin caused a significant fall in number of lung lymph leukocytes (T1, T4 and T8 cells) from 120 minutes; numbers of B lymphocytes were also reduced. Counts of the number of lymphocytes in the biopsy tissue revealed a significant rise in T lymphocytes sequestered in the lung. We conclude endotoxemia in sheep causes a reduction in lymphocytes in blood and lung lymph and an increase in these cell types in peripheral lung tissue. These findings suggest that lymphocyte subpopulations accumulate in the lungs during periods of pulmonary hypertension and increased permeability and may participate in endotoxin-induced lung injury.

Animals

Ciguatera and mannitol: experience with a new treatment regimen.

Ciguatera is a distressing, hitherto-untreatable and not rare disease which results from the eating of ciguatoxin-contaminated fish from tropical and subtropical waters. We report here the results of a pilot study to assess the efficacy of mannitol therapy in ciguatera poisoning. Twelve adult patients (six men) have been treated, five of whom--who were ill acutely--experienced a significant benefit from this therapy, in three cases, with a hitherto-unexperienced dramatic reversal of symptoms. We conclude that an intravenous infusion of 1.0 g/kg of mannitol which is given over 45 minutes, after rehydration if required, can be of significant benefit to at least some acutely intoxicated victims. We postulate either a reduction of axonal oedema, or a scavenger effect, or both, as the mechanism of the beneficial effects of mannitol. Ciguatoxin is rich in hydroxyl groups, and causes microscopic oedema of neural tissue. If our conclusion of the beneficial effects of mannitol therapy is confirmed, this will offer the first effective therapy for acute phases of this disease, and has promise of preventing much long-term morbidity.

Acute Disease

In vivo transfection of murine lungs with a functioning prokaryotic gene using a liposome vehicle.

The authors report successful in vivo transfection of lungs of mice with a functioning prokaryotic gene encoding the intracellular enzyme, chloramphenicol acetyltransferase (CAT). Transfection was accomplished by injecting a plasmid containing the coding region for CAT driven by the SV40 early promoter (pSV2CAT) complexed to specially synthesized cationic liposomes. Intravenous or intratracheal injection of DNA-liposomes resulted in expression of the CAT gene in the lungs, persisting for at least a week, with little enzyme activity detectable in systemic organs. This method should permit either transient or stable in vivo transfection of the lungs with a gene encoding any protein of interest, providing a powerful experimental tool and potentially a novel and broadly applicable clinical therapeutic technique.

Acetylation

Expression of a prokaryotic gene in cultured lung endothelial cells after lipofection with a plasmid vector.

Transfection of cultured cells with functioning foreign genes can be a powerful tool for delineating mechanisms controlling gene expression and for manipulating cellular synthetic machinery. We transfected cultured bovine pulmonary artery endothelial cells with a plasmid (pRSVCAT) containing the prokaryotic gene, chloramphenicol acetyltransferase (CAT), driven by a Rous sarcoma virus (RSV) promoter. Transfection was accomplished by binding the plasmid DNA to specially synthesized cationic liposomes and incubating cell monolayers with the liposome-DNA complex (a process called lipofection). We found marked CAT expression in endothelial cells by 24 h after lipofection (complete chloramphenicol acetylation in a 4-h assay incubation with less than 0.1 mg cell protein). Marked CAT expression persisted after splitting the cells 1:2 at 6 days after lipofection. Detectable CAT activity was present 14 days after lipofection following two 1:2 splits of the cells. CAT expression was related to the quantity of plasmid DNA used for lipofection; 1.0 micrograms DNA per 60-mm dish of cells resulted in less CAT activity at 48 h than did 5 or 10 micrograms DNA per dish. Ten micrograms of DNA-liposome complex per dish caused substantial numbers of endothelial cells to detach from the dish, but little cytotoxic effect was seen with 5 or 1 micrograms DNA-liposome complex per dish. This simple, highly efficient method for introducing functioning foreign genes into cultured endothelial cells will permit a broad range of studies of molecular mechanisms of endothelial cell function and studies of the consequences of highly specific modifications in protein synthesis on endothelial responses.

Animals

Chest pain evaluation unit: a cost-effective approach for ruling out acute myocardial infarction.

We compared a "cardiac profile" test with standard creatine kinase (CK) and lactic dehydrogenase (LD) electrophoresis in 798 cases of possible acute myocardial infarction (MI). The cardiac profile enzyme screen (CK-B, CK, LD) used on 495 patients who came to the emergency department with chest pain suggestive of acute MI but without diagnostic ECG changes. Instead of admission to the coronary care unit, they were placed on observation status (Chest Pain Evaluation Unit) for a period up to 20 hours (average 11.1 hours). Using the results of the cardiac profile, 327 were able to be sent home. Of the 168 patients admitted, only 30 (18%) had subsequent enzyme evidence of myocardial necrosis. Use of the chest pain evaluation unit resulted in an 80% reduction in cost of ruling out acute MI for the 327 patients not admitted.

Adult

Gynaecological cytology screening in South Australia: a 23-year experience.

The Cytology Laboratory at The Queen Elizabeth Hospital, Adelaide, processed 630,131 gynaecological smears from 347,389 patients between September 1, 1959 and July 31, 1982. The data suggested a lack of compliance with the recommendations of screening frequency, with an average of only 1.8 smear-tests per woman being performed during the 23-year study period. There was a two-fold increase in the incidence of histologically-confirmed cervical dysplasia and carcinoma-in-situ from 1977, but no increase in the incidence of invasive carcinoma. The age distributions of the incidence of dysplasia and carcinoma-in-situ moved towards younger age-groups during the study period. By the end of the study period (1977-1981), the incidence peaks of dysplasia and carcinoma-in-situ were both at ages 25 to 34 years compared with 30 to 39 years of age and 35 to 44 years of age, respectively, in 1962-1966. Invasive carcinoma had a much broader age distribution, with two incidence peaks, and the distribution shifted towards older age groups. The first peak had moved from 40 to 49 years of age (1962-1966) to 50 to 59 years of age (1977-1981) and the second peak moved from 60 to 69 years of age to 75 to 84 years of age. Error rates in cytological assessment were determined by comparing the histological diagnosis with the result of the most recent smear-test. By means of this method the sensitivity was 84.6%. The sensitivity was increased to 91.4% if the estimate were based on the most abnormal result of a smear-test before the histological diagnosis. A poor correlation was found between a mildly-atypical (inflammatory) cytological result (class 2) and a benign histological diagnosis: 48% of class-2 smears were diagnosed histologically as dysplasia or worse. In very few of these cases had an elapsed time of more than five years occurred between the class-2 result of a smear-test and the subsequent diagnosis of neoplasia. Thus, the majority of these cases were either underdiagnosed by cytology or had developed within five years, which indicates the importance of the careful follow-up of women with class-2 smears. Finally, the data illustrate the ability of gynaecological cytology screening to assist in the detection of extracervical gynaecological neoplasms of the uterus, ovary, vagina and vulva, as 132 such cases were diagnosed during the study period after positive results of a smear-test led to further investigations.

Adult