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Biomedical subjects

M Kerr

Publications and source records attributed to M Kerr.

At least 37 records · Page 2Linked to original sources

Disruptiveness, friends' characteristics, and delinquency in early adolescence: a test of two competing models of development.

This study tested 2 competing models of friends' influence on the development of delinquency in disruptive boys. In so doing, we examined whether highly disruptive, moderately disruptive, moderately conforming, and highly conforming boys' delinquency increased or decreased depending on their friends' characteristics. A sample of 868 boys was classified into the 4 groups according to teacher ratings at ages 11 and 12. Each group was then subdivided by mutual friends' peer-rated aggressiveness-disturbance at the same ages: aggressive-disturbing friends, average friends, nonaggressive-nondisturbing friends, and no friends. Subgroups were next compared on self-reported delinquency at age 13 while controlling for average self-reported delinquency and socioeconomic variables at ages 11 and 12. Results indicate that moderately disruptive boys with aggressive-disturbing friends were more delinquent at age 13 than other subgroups of moderately disruptive boys. Highly disruptive and conforming boys, however, were unaffected by their friends' characteristics. We conclude that the results partially support each theoretical model, suggesting that both individual characteristics and deviant peer association might play causal roles.

Adolescent

Inhibition of rat parotid gland growth response induced by chronic isoproterenol following treatment with quinolone antibiotics.

While antibiotics are broadly used in dental and medical therapy, little attention has been directed towards the potential toxic side effects of antibiotics on tissue regeneration. Here we examined the effect of a quinolone antibiotic, pefloxacin (Rhone Poulenc) on rat parotid gland responses to chronic isoproterenol treatment. Groups of rats received injections of isoproterenol to induce glandular growth, saline (controls), pefloxacin, or isoproterenol and pefloxacin in combination. Parotid gland weight decreased significantly after pefloxacin treatment for 7 days as well as inhibiting glandular enlargement provoked by isoproterenol. The same trend was observed for the rates of DNA synthesis, with the incorporation of [3H]-thymidine in isoproterenol/pefloxacin-treated rats reduced to 49% of isoproterenol treatment alone levels. Saline-treated animals were 42% of the rate of [3H]-thymidine incorporation into DNA observed in isoproterenol treated rats. While isoproterenol treatment increased steady-state mRNA levels for fos, jun, myc, src, c-erbB-2, ras and topo II, inclusion of pefloxacin with the isoproterenol regimen blocked these increases. Pefloxacin treatment by itself did not alter proto-oncogene mRNA levels in the parotid gland. Glandular amylase activity was decreased in the pefloxacin treated group, while the combination of isoproterenol with pefloxacin did not decrease glandular amylase levels to the extent of that observed with beta-agonist treatment alone. In acute experiments, pefloxacin significantly decreased the volume of saliva secreted by the parotid gland. These results suggest that quinolone-based antibiotics disturb the secretory function of the parotid gland and can inhibit cell proliferation and regeneration.

Adrenergic beta-Agonists

Alterations in the level of phosphotyrosine signal transduction constituents in human parotid tumors.

Human parotid tumors were evaluated for the activation of the phosphotyrosine signaling pathway by Western blot, enzyme activity assay, and reverse transcriptase-polymerase chain reaction. Warthin's tumor and mucoepidermoid carcinomas had the greatest level of tyrosine phosphorylated proteins identified in plasma membrane fractions. These tumors, along with pleomorphic adenocarcinoma, showed high levels of membrane expression of the tyrosine kinase receptor, c-erbB-2, and phosphatidylinositol-3-kinase. Expression of the epidermal growth factor receptor was confined to normal tissue. The level of mRNA for c-erb was elevated only in mucoepidermoid carcinomas. Messenger RNA levels for ras were unchanged from control levels in all tumors, while the level of src mRNA was higher in the tumor samples than the normal parotid tissue. The activities of several signal transduction kinases, including protein kinase A and C were elevated in tumor tissue (7.7- to 18.9- and 0.4- to 3.7-fold higher, respectively), relative to surrounding normal tissue. While the level of glandular amylase was reduced (22%-0% of normal levels) in the tumor tissue, epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha) content was dramatically higher in the neoplastic tissue (10- to 170-fold and 4.6- to 6.0-fold, respectively). These results suggest that with the presence of elevated levels of EGF, TGFalpha, and the oncoprotein receptor c-erbB-2 in the membrane of parotid tumors, cell proliferation and activation of the phosphotyrosine signal transduction pathway may involve autocrine stimulation through the expression of high levels of growth factor and receptor in the same tissue.

Base Sequence

Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region.

Linkage analysis in separately ascertained families of probands with juvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated "EJM1"), on chromosome 6p, predisposing to a trait defined as either clinical JME, its associated electroencephalographic abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed in 19 families in which a proband and at least one first- or two second-degree relatives have clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was carried out under the assumptions of autosomal dominant inheritance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region formally excluded (LOD score < -2) by using multipoint analysis varies depending on the assumptions made concerning inheritance parameters and the proportion of linked families, alpha-that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected individuals as unknown or excluding a subset of four families in which pyknoleptic absence seizures were present in one or more individuals did not alter these conclusions.

Adolescent

Attitudes of general practitioners to caring for people with learning disability.

BACKGROUND: The views of general practitioners on their increasing role in caring for people with learning disability in the community are not known. AIM: A study was carried out to assess the views of general practitioners with regard to providing routine care, organizing health promotion and specific health checks for people with learning disability and the role of specialists. METHOD: A postal questionnaire was sent to all 242 general practitioners in Gwent, south Wales. Participants had to mark their level of agreement with 20 attitude statements regarding learning disability. RESULTS: A total of 126 general practitioners (52%) responded. Respondents generally agreed that general practitioners were responsible for the medical care of people with learning disability. Respondents tended to be opposed to providing regular structured health promotion for people with learning disability, such as annual health checks and assessing hearing and eyesight. Specialist services were generally valued by respondents. CONCLUSION: General practitioners largely accepted their role as primary health care providers for people with learning disability. In contrast, their role as providers of health promotion for this patient group was not generally accepted. Further research into the appropriateness and opportunity costs of health screening for people with learning disability is needed.

Attitude of Health Personnel

Detection of insulin and insulin-like growth factors I and II in saliva and potential synthesis in the salivary glands of mice. Effects of type 1 diabetes mellitus.

The salivary glands of mammals synthesize and secrete a number of peptide growth factors that play important roles in cell/tissue homeostasis and embryonic development. Using a radioimmunoassay, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) were detected in saliva from mice. Unlike epidermal growth factor (EGF), there was no sexual dimorphism in the concentrations of the insulin growth factor family. Immunohistochemical localization of IGF-I and IGF-II was confined to the duct cells of both the parotid and the submandibular glands. Reverse transcriptase-polymerase chain reaction amplification of total RNA from parotid and submandibular glands confirmed the presence of all three hormone/growth factor mRNAs in both glands. The levels of insulin and IGF-I were higher in saliva from an animal model for autoimmune type 1 diabetes, the non-obese diabetic (NOD) mouse, than in a second inbred strain, BALB/c. In contrast, the IGF-II levels were decreased relative to the BALB/c strain. With the onset of diabetes in NOD mice, insulin levels declined, while IGF-I and IGF-II levels showed trends toward lower levels of these growth factors when compared with non-diabetic animals. These changes were reflected in the concentrations from parotid and submandibular gland cell lysates.

Animals

Lactation is disrupted by alpha-lactalbumin deficiency and can be restored by human alpha-lactalbumin gene replacement in mice.

Mice carrying either a deletion of the murine alpha-lactalbumin (alpha-lac) gene (null allele) or its replacement by the human alpha-lac gene (humanized allele) have been generated by gene targeting. Homozygous null females are alpha-lac-deficient, produce reduced amounts of thickened milk containing little or no lactose, and cannot sustain their offspring. This provides definitive evidence that alpha-lac is required for lactose synthesis and that lactose is important for milk production. Females homozygous for the humanized allele lactate normally, indicating that human alpha-lac can replace murine alpha-lac. Mouse and human alpha-lac expression was compared in mice heterozygous for the humanized allele. The human gene expressed approximately 15-fold greater mRNA and approximately 14-fold greater protein than the mouse, indicating that the major determinants of human alpha-lac expression are close to, or within, the human gene and that the mouse locus does not exert a negative influence on alpha-lac expression. Variations in alpha-lac expression levels in nondeficient mice did not affect milk lactose concentration, but the volume of milk increased slightly in mice homozygous for the humanized allele. These variations demonstrated that alpha-lac expression in mice is gene dosage dependent.

Alleles

Effect of EGF on rat parotid gland secretory function.

The present study reports changes in saliva composition from the rat parotid gland in response to single and repeated administration of epidermal growth factor (EGF). Treatment of rats with EGF (10 micrograms/kg, i.p., twice daily for 3 days) caused an increase in amylase activity in saliva collected from cannulated parotid duct, following stimulation of secretion with pilocarpine, with a corresponding decrease in enzyme activity in the gland. Analysis of parotid gland RNA by reverse transcriptase-PCR generated a single predicted amylase-derived cDNA product of 576 bp. The steady-state levels of mRNA for amylase from EGF-treated parotid total RNA showed a 1.8-fold increase compared to untreated controls. A single dose of EGF (15 min following i.p. injection) elicited an activation of both protein kinase A and protein kinase C activities. While the activation of protein kinase A was still maintained under the chronic EGF regimen, the activity levels of protein kinase C showed down-regulation to untreated control values.

Amylases

General practitioners and psychiatrists: comparison of attitudes to depression using the depression attitude questionnaire.

BACKGROUND: Variation in the management of depression may be linked to doctors' attitudes to depression. AIM: A study was undertaken comparing the attitudes to depression between general practitioners and psychiatrists. METHOD: A sample of 74 general practitioners and 65 psychiatrists in Wales was surveyed by postal questionnaire. Attitudes were assessed by the depression attitude questionnaire and patient management was assessed by a questionnaire on prescribing practice. RESULTS: General practitioners differed significantly from psychiatrists in attitudes, particularly in areas covering professional ease in dealing with patients with depression and identification of depression. Those general practitioners who reported use of low antidepressant doses were significantly more likely than general practitioners prescribing standard doses to believe in psychotherapeutic treatments. Users of short-term continuation therapy expressed a lack of therapeutic optimism and comfort in dealing with depressed patients. CONCLUSION: General practitioners and psychiatrists differ significantly in their attitudes to depression. The attitudes which vary among general practitioners reflect practice. The depression attitude questionnaire may prove useful in indicating how educational initiatives to improve primary care detection and management should be directed.

Attitude of Health Personnel

Characterization of the synthesis and expression of the GTA-kinase from transformed and normal rodent cells.

The murine transformed cell line YC-8 and beta-adrenergic receptor agonist (isoproternol) treated rat and mouse parotid gland acinar cells ectopically express cell surface beta 1-4 galactosyltransferase during active proliferation. This activity is dependent upon the expression of the GTA-kinase (p58) in these cells. Using total RNA, cDNA clones for the protein coding region of the kinase were isolated by reverse transcriptase-PCR cloning. DNA sequence analysis failed to show sequence differences with the normal homolog from mouse cells although Southern blot analysis of YC-8, and a second cell line KI81, indicated changes in the restriction enzyme digestion profile relative to murine cell lines which do not express cell surface galactosyltransferase. The rat cDNA clone from isoproterenol-treated salivary glands showed a high degree of protein and nucleic acid sequence homology to the GTA-kinase from both murine and human sources. Northern blot analysis of YC-8 and a control cell line LSTRA revealed the synthesis of a major 3.0 kb mRNA from both cell lines plus the unique expression of a 4.5 kb mRNA in the YC-8 cells. Reverse transcriptase-PCR of LSTRA and YC-8 confirmed the increased steady state levels of the GTA-kinase mRNA in YC-8. In the mouse, induction of cell proliferation by isoproterenol resulted in a 50-fold increase in steady state mRNA levels for the kinase over the low level of expression in quiescent cells. Expression of the rat 3' untranslated region in rat parotid cells in vitro led to an increased rate of DNA synthesis, cell number an ectopic expression of cell surface galactosyltransferase in the sense orientation. Antisense expression or vector alone did not alter growth characteristics of acinar cells. A polyclonal antibody monospecific to a murine amino terminal peptide sequence revealed a uniform distribution of GTA-kinase over the cytoplasm of acinar and duct cells of control mouse parotid glands. However, upon growth stimulation, kinase was detected primarily in a perinuclear and nuclear immunostaining pattern. Western blot analysis confirmed a translocation from a cytoplasmic localization in both LSTRA and quiescent salivary cells to a membrane-associated localization in YC-8 and proliferating salivary cells.

Amino Acid Sequence

Chemotherapy prolongs survival in inoperable pancreatic carcinoma.

Forty-three patients with irresectable advanced pancreatic cancer were randomized to receive chemotherapy using a combination of 5-fluorouracil, Adriamycin and mitomycin or no chemotherapy. Groups were well matched with regard to age, extent of disease and performance status on entry. Chemotherapy was well tolerated and, although common, side-effects were usually mild. Psychological measurements based on the Hospital Anxiety and Depression score were made in 31 patients. These showed significantly less depression but not anxiety in the treated group immediately after randomization and following 2 months of chemotherapy. Median survival in the treated group was 33 (range 9-80) weeks compared with 15 (range 1-62) weeks in the untreated group (P < 0.002). Chemotherapy should be considered in all patients presenting with advanced inoperable pancreatic cancer.

Adult

Increasing opportunities for requesting in classrooms serving children with developmental disabilities.

Evaluated an intervention package for increasing requesting opportunities in special education classrooms. Five teachers, serving 26 children with moderate to severe disabilities, received in-service training, consultation, and feedback on the use of three strategies designed to create opportunities for requesting (i.e., missing item, interrupted chain, delayed assistance). Observations were conducted in a multiple-baseline across classrooms design to record the number and types of opportunities provided by each teacher. During baseline, few opportunities for requesting were observed. The number of opportunities for requesting and the number of correct student responses increased during intervention. Opportunities continued to be provided during generalization and follow-up sessions. The study demonstrated an effective strategy for helping teachers incorporate opportunities for functional communication into the natural environment.

Adolescent

Opportunities for communication in classrooms serving children with developmental disabilities.

Documented the number and types of opportunities for communication provided by teachers in seven classrooms for children with developmental disabilities and by teachers of nonhandicapped preschoolers in a day care center. In the special education settings, less than 14% of the more than 6,000 observation intervals contained an opportunity for communication. Most opportunities involved naming an object or event followed in frequency by opportunities to request, answer, and imitate. Similar results were obtained in the day care center. In the special education classrooms, a strong positive correlation was found between a child's existing communication skills and the number of opportunities received. Results suggest that these teachers did incorporate opportunities for communication into classroom activities.

Adolescent

Phenotypic variability of familial adenomatous polyposis in 11 unrelated families with identical APC gene mutation.

BACKGROUND/AIMS: Familial adenomatous polyposis is caused by germline mutation of the adenomatous polyposis coli (APC) gene. Affected individuals develop hundreds of colorectal adenomas at young age and can have extracolonic lesions. METHODS: This study evaluated the phenotype of 74 patients with familial adenomatous polyposis from 11 unrelated families with an identical 5-base pair deletion at codon 1309 of the APC gene. RESULTS: Polyp density in the sigmoid colon of 16 patients from 9 families varied from 3.8 to 13.1/cm2, and mean polyp diameter ranged from 1.4 +/- 0.1 to 2.7 +/- 0.1 mm. The distribution of colonic adenomas also varied, with diffuse polyposis in 6 patients but relative polyp sparing in the more proximal colon in 6 others. Age at diagnosis of colorectal cancer ranged from 19 to 62 years, but the mean age did not differ among the 4 families with multiple cases. Colorectal cancers occurred predominantly in the rectosigmoid (80%) but also in the more proximal colon. The percentage of patients affected by various extracolonic lesions differed widely among and within the 11 families (range, 0%-100%). CONCLUSIONS: APC gene mutation at codon 1309 results in intrafamily and interfamily phenotypic variation in familial adenomatous polyposis. Environmental and/or other genetic factors must play roles in the expression of germline APC gene mutations.

Adenomatous Polyposis Coli

A survey of aggressive behaviour among a population of persons with intellectual disability in Queensland.

A survey was conducted on aggressive behaviour within a population of 2412 persons with intellectual disability in Queensland, Australia. Two hundred and sixty-one individuals were identified who engaged in at least one form of aggressive behaviour, yielding an overall prevalence of 11%. The relative prevalence of aggressive behaviour was higher among institutionalized persons (35%) when compared to those living in group homes (17%) or other community-based facilities (3%). The aggressive behaviour sample included a higher percentage of males (64%). Most were described as functioning in the severe/profound (54%) or moderate (31%) range of intellectual disability with one-third having no intelligible speech. Two-thirds of the sample received medication for their challenging behaviour, while only one-third had behavioural programmes. Eighty per cent engaged in three or more forms of aggression. Many also displayed self-injury (34%) or property destruction (30%). Surveys of aggressive behaviour may prove useful for coordinating services.

Adolescent

Case managers and physicians: communication and perceived problems.

OBJECTIVE: To describe case managers' perceptions of the physician-case manager relationship. DESIGN: A qualitative field study using in-depth open-ended interviews was used to elicit case managers' experiences and practices. A multidisciplinary team analyzed transcripts using an adaptation of the "grounded theory" approach of Glaser and Strauss. PARTICIPANTS/SETTING: Case managers were selected for interview using a maximum variation sampling strategy within an established state-wide case management agency. MAIN OUTCOME MEASURES: Transcript analysis allowed for the organization of observations into themes, which were merged across interviews to generate theses. RESULTS: Case managers report that: (1) The case manager role is poorly understood by physicians. (2) Physicians lack insight into the social and environmental aspects of home-bound elderly people. (3) Access to physician services is often difficult to obtain. (4) Power struggles occasionally surface in care planning. (5) Decisions by physicians and case managers regarding the care of frail elderly are often made from different agenda. CONCLUSIONS: From the perspective of case managers, gaps in interprofessional communication may hinder the optimal care of frail elderly individuals.

Aged

"Stockless" cost reduction in the operating room.

St. Paul-Ramsey Medical Center in St. Paul, MN became one of the first hospitals in the United States to initiate a "stockless" par level inventory system. Successes with stockless led the hospital to look at implementing it in the OR to achieve a reduction of expense to revenue. Materiel Management and Surgical Services discussed a number of issues relevant to implementing a stockless program, including product flow, accuracy and cost of case carts and preference cards, item pricing, committed usage of items brought into the system and establishment of a steering committee. Specific OR issues and practices required evaluation and adjustment, such as the routine use of emergency direct ordering. Information systems support was brought in and a products committee established to do education and oversee the program. Savings for 1993-94 were $185,146.

Cost Savings