Biomedical subjects
Publications and source records attributed to G King.
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.
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.
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.
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.
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.
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.
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.
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.
Social workers are in an ideal position to identify, refer, and treat alcoholic patients. However, they need special training and specific work experience. The authors discuss the credentialing program for alcoholism counselors in New York State as well as effective treatment applications.
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.
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.
A comparison of tooth movement cycles and changes in alveolar tissue mineral densities was made between young (21 to 28 days old) and adult (90 to 100 days old) rats. An initial 60-g mesial tipping force was applied to the maxillary first molars; tooth movement was estimated by measuring the opening between first and second molars, and tissue mineral density by sample ash weight per cubic centimeter. A characteristic three-part tooth movement cycle was found in both groups of rats. This cycle consists of an early "instantaneous" movement that is a function of the viscoelastic properties of the tissues, a delay period during which little tooth movement occurs due to hyalinization and undermining resorption, and a late period during which bone remodeling and tooth movement occur. Compared with the adult group, the amount of "instantaneous" movement in the young rats was greater (P less than 0.001), the delay period was shorter, and the rate of late tooth movement was faster (P less than 0.001). The young rats had significantly lower (P less than 0.05) mineral densities before orthodontic treatment. Both groups experienced a slight but insignificant increase in density followed by rapid declines to a nadir that was not different between the groups. The young rats reached this point by day 5 and the adults by day 7. The point of lowest mineral density occurred in the treated alveolar tissues toward the end of the delay period for each group and was followed by a return to control values at rates that were not significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic forms of severe insulin resistance are often characterized by alterations in binding and/or kinase properties of the insulin receptor. To evaluate whether alterations in insulin receptor kinase of erythrocytes can be used as genetic markers, we studied patients with two apparently inherited conditions of severe insulin resistance (leprechaunism and the type A syndrome of insulin resistance) and their families. In the two propositi, [125I]insulin binding to intact erythrocytes was decreased by 64% and 45%, respectively. This was primarily due to a decrease in receptor number and was found in intact cells and solubilization of the receptors. Similar insulin binding defects were found on monocytes. Insulin-stimulated tyrosine kinase activity of the solubilized receptor from erythrocytes was also decreased and to a similar extent as binding. Parents of neither patient had clinical manifestations of leprechaunism or the type A syndrome. Furthermore, no alterations in insulin receptor binding or kinase activity were found in erythrocytes from the mothers. Insulin binding in the father of the type A patient was also normal, whereas the father of the leprechaun had decreased receptor affinity. Receptors extracted from the both fathers' cells had a 40-60% decrease in maximal insulin-stimulated phosphorylation and significant rightward shifts of the insulin dose-response curves (ED50, 141 and 42 ng/mL, respectively; control ED50, 16 ng/mL). The finding of biochemical defects in insulin receptor kinase activity in clinically unaffected parents of patients suggests that these alterations may be useful genetic markers and more sensitive than insulin binding studies for studying pattern of inheritance of these diseases.
The history, reality, and prolonged effects of racial stratification and its supportive ideology in the United States require systematic study of the impact of racial perceptions in the health sphere and in every facet of American life (Berry 1965; Berreman 1985; Blackwell 1985). In this regard, the use of race as an independent variable in social research is, in principle, similar to the presumed explanatory power of other status characteristics such as class or economic position. Depending on which meaning is intended, the potential policy, health services, and sociopolitical outcomes could be diametrically opposed to one another. Far from being an esoteric subject among intellectuals, any definition of race has fundamental and practical extensions to cultural and political realities. Essentially, studies and discussions of racial similarities and differences in health matters, whether intended or not, go beyond statistical compilations and correlations and reflect norms, values, the country's common beliefs (Praeger 1982), and the structural positions of majority and minority groups. Presumably, these are among the reasons that racial categories are studied in social science. They are assumed to represent socially relevant and unique histories, experiences, and statuses which differentiate black and white Americans in particular. The risks in epidemiologic and in social science research involve the preoccupation with disparities in the health difficulties among them; the attribution of racial biology and genetic traits to virtually all health spheres; the assumed preponderance of disabling conditions for blacks; and the unrelenting focus on only two racial populations despite our having a multiethnic society (Wilkinson 1987). Since health behaviors are directly associated with a group's "way of life," they should be carefully scrutinized within relevant socio-environmental contexts as part of the scientific processes of discovery, for the underlying premises, ideological translations, and practical applications of their studies especially with respect to race-specific health research. It is likely that systematic probing beyond demographic or constitutional factors will enable social scientists and health researchers to discover that for certain behaviors (e.g., prevention), individual attributes such as race and sex--and even knowledge, roles, attitudes, and diets--may explain far less than will environmental hazards and basic structural variables such as the organization of the health care delivery system, availability of and access to care, ability to pay, provider patterns, diagnostic processes, institutional operations, and quality of care.(ABSTRACT TRUNCATED AT 400 WORDS)
Evaluation of the free energy of ionization of acidic groups in proteins may be used as a powerful and general test case for determining the reliability of calculations of electrostatic energies in macromolecules. This work attacks this test case by using an adiabatic charging process that evaluates the changes in free energies associated with ionizing the acidic groups Asp-3 and Glu-7 in bovine pancreatic trypsin inhibitor and aspartic acid in solution. The results of these free energy calculations are very encouraging; the error range is about 1 kcal/mol for these free energy changes of about-70 kcal/mol. This indicates that we are finally approaching the stage of obtaining quantitative results in modeling the energetics of solvated proteins.
Monoclonal antibodies were used to analyse skin samples from human fetuses (15-19 weeks gestational age) for the presence of class II major histocompatibility antigens (HLA-DR, DQ and DP). Cells expressing these antigens were clearly demonstrated within the epidermis from a proportion (4/7) of cases and were completely absent from the others. The negative samples were uniformly those with an epidermis of three cell layers or less. Such material may prove useful in studying the induction of class II antigen expression and the role of these antigens in allostimulation.
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