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Biomedical subjects

M Hammond

Publications and source records attributed to M Hammond.

At least 37 records · Page 2Linked to original sources

Functional lung unit in the pig.

To study the size of the vessels supplying the functional lung unit, polystyrene beads of uniform diameter were injected intravenously in anaesthetised pigs and subsequent gas exchange abnormalities were studied using the multiple inert gas elimination technique. Beads of different sizes, ranging from 63 to 262 microm, were used, each pig receiving beads of only one size. Successive 0.25 g boli of beads (cumulative dose 1.0-1.5 g) increased shunt (from 3% baseline to 20% of cardiac output) and pulmonary artery mean pressure (from 26 to 45 mmHg) and decreased arterial P(O(2)) (from 96 to 43 mmHg) and cardiac output from 2.8 to 2.2 L min(-1) with no differences according to bead sizes. The dispersion of the ventilation dist ribution (log SDV), normal at 0.39 before beads, increased progressively with bead size from 0.48 (63 microm to 0.91 (262 microm). The 63 microm beads were lodged in vessels associated with respiratory bronchioles and smaller airways, whereas larger beads were positioned in vessels associated with non-respiratory airways. A linear correlation analysis between log SDV and bead size showed that 59 microm beads produce a log SDV that is 2 SEM above mean baseline log SDV. These findings suggest that the functional lung unit in this species (with no collateral ventilation) is smaller than in a species of the same size and with collateral ventilation (dog) in whom occlusion of 124 microm or larger diameter vessels is required to increase log SDV.

Animals↗

Analysis of the distribution of HLA-A alleles in populations from five continents.

The variation and frequency of HLA-A genotypes were established by PCR-SSOP typing in diverse geographically distributed populations: Brazilian, Colombian Kogui, Cuban, Mexican, Omani, Singapore Chinese, and South African Zulu. HLA-A allelic families with only one allele were identified for HLA-A*01, -A*23, -A*25, -A*31, -A*32, -A*36, -A*43, -A*69, -A*80; and with two alleles for HLA-A*03, -A*11, -A*26, -A*29, -A*33, -A*34, and -A*66. Greater variation was detected for HLA-A*02, -A*24, and -A*68 allele families. Colombian Kogui and Mexican Seris showed the least diversity with respect to HLA-A alleles, albeit with small numbers tested, with only four and five HLA-A alleles identified, respectively. It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation.

Africa↗

Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and caucasoid adults and children.

Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus. Cohorts evaluated included 44 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17(Gag) and p24(Gag) sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However, there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17(Gag) peptide residues 16 to 30 (38 versus 12%; P < 0.01), while p24(Gag) peptide residues 41 to 60 contained the dominant Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005). Within this 20-mer p24(Gag), an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design.

Adult↗

Do you CARE? A national register for cleft lip and palate patients.

The Cleft Palate Index and more recently the Craniofacial Anomalies Register--CARE--have been in operation since 1982. This paper summarises its development and plans for the future. CARE is a multi-disciplinary committee involving all specialties involved in the treatment of this group of patients. It therefore should and can be well placed to coordinate the cleft data arising from these patients.

Cleft Lip↗

Do you care? A national register for cleft lip and palate patients.

The Cleft Palate Index and, more recently, the Craniofacial Anomalies Register--CARE--have been in operation since 1982. This paper summarizes its development and plans for the future. CARE is a multidisciplinary committee involving all specialties involved in the treatment of this group of patients therefore it should and can be well placed to co-ordinate the cleft data arising from these patients.

Cleft Lip↗

Marital conflict management skills, parenting style, and early-onset conduct problems: processes and pathways.

This study examined whether the link between marital conflict management style and child conduct problems with peers and parents is direct or mediated by mothers' and fathers' parenting style (critical parenting and low emotional responsivity). One hundred and twenty children, aged 4 to 7 years, were observed interacting in our laboratory playroom solving a problem with their best friend as well as at home with their parents. In addition, all the children's parents were observed in our laboratory trying to solve two family problems as well as at home interacting under more natural conditions with each other and with their children. Mothers and fathers completed questionnaires assessing marital problem solving as well as reports of their children's behavior problems. Results indicated that a negative marital conflict management style had direct links with children's conduct problems. In addition, the linkage between negative marital conflict management and children's interactions with parents and peers was found to be mediated by both mothers' and fathers' critical parenting and low emotional responsivity, thereby supporting the indirect as well as the direct model of negative family interactions. The findings are discussed in relation to the implications for treatment.

Adaptation, Psychological↗

The natural history of an HLA haplotype and its recombinants.

The presence of haplotype-specific recombination sites can be determined by analyzing the conservation of extended haplotypes in the population. This approach considers all meioses in the history of the population and requires the presence of characteristic markers that easily allow the identification of the haplotype or of its recombined segments. The recombination breakpoint can then be mapped by looking for shared alleles between haplotypes selected through the specific marker/s. We identified a rare perfect tandem duplication of a 145 base pair segment in the LTA promoter, which tags a B60 (B60D) haplotype. The duplication was detected in 16/90 B60+ Europeans, while absent in 101 B60+ Orientals. The conservation of the class I end and the extreme variability of the class II end suggested that the present-day B60D haplotypes originated from an ancestral haplotype by recombination events centromeric to the duplicated sequence. Through a fine mapping using markers of the HLA central region a preferential recombination site was localized in the 60 kilobase interval between TNFd,e, and D6S273/K11 Amicrosatellite loci (i.e., between LST1 and BAT3 genes). This site behaves as a potent recombination enhancer leading to fragmentation in most of the extant B60D haplotypes and can be considered responsible for their "instability". In the relatively recently founded Finnish population, where the LST1/BAT3 interval recombination has probably not yet had the chance to occur, a founder effect can explain the presence of a rare DP (DPB1(*)1601) allele in most B60D haplotypes in this population.

Base Sequence↗

Conduct problems and level of social competence in Head Start children: prevalence, pervasiveness, and associated risk factors.

The purpose of the current project was to determine the prevalence of conduct problems, low social competence, and associated risk factors in a sample of 4-year-old low-income children (N = 426) from 64 Head Start classrooms in the Seattle area. Conduct problems and social competence were assessed based on a combination of teacher reports, parent reports, and independent observations of children interacting with peers in the classroom and with parents at home. We examined the relative contribution of a variety of risk factors, including maternal history and socioeconomic background, current levels of stress and social support, mothers' emotional state, and parenting competence in relation to "pervasive" (i.e., at home and school) and "nonpervasive" conduct problems and low social competence. Findings indicated similar risk factors for conduct problems and for low social competence, with an ordered increase in the number of risk factors from normal to "nonpervasive" to "pervasive" groups. Harshness of parenting style (i.e., slapping, hitting, yelling) significantly distinguished between the three groups for low social competence and conduct problems. Positive affect, praise, and physical warmth from mothers were positively related to social competence but unrelated to conduct problems.

Child Behavior Disorders↗

How does alendronate inhibit protein-tyrosine phosphatases?

Alendronate (4-amino-1-hydroxybutylidene 1,1-bisphosphonate) is a drug used in the treatment of osteoporosis and other bone diseases. The inhibition of protein-tyrosine phosphatases (PTPs) by alendronate suggests that PTPs may be molecular targets. As a clear understanding of the inhibition mechanism is lacking, our aim was to analyze the mechanism to provide further insight into its therapeutic effect. We show here that the inhibition of PTPs by alendronate in the presence of calcium followed first-order kinetic behavior, and kinetic parameters for the process were determined. Evidence is presented that the inhibition by alendronate/calcium is active site-directed. However, this process was very sensitive to assay constituents such as EDTA and dithiothreitol. Furthermore, the inhibition of PTPs by alendronate/calcium was eliminated by the addition of catalase. These observations suggest that a combination of alendronate, metal ions, and hydrogen peroxide is responsible for the inhibition of PTPs. The individual effects of alendronate, calcium, or hydrogen peroxide on the inactivation of CD45 were determined. Electrospray ionization mass spectrometry demonstrated that the mass of PTP1B increased by 34 +/- 2 units after the enzyme was inactivated with alendronate/calcium, due to the oxidization of the catalytic cysteine to sulfinic acid (Cys-SO2H). The inhibited PTP1B could be partially reactivated by treatment with reducing agents such as hydroxylamine (NH2OH) and N,N'-dimethyl-N, N'-bis(mercaptoacetyl)hydrazine, indicating the presence of other oxidized forms such as sulfenic acid (Cys-SOH). This further confirms that the inhibition is the result of oxidation of the catalytic cysteine. The relevance of this oxidative inhibition mechanism in a biological system is discussed.

Alendronate↗

Placebo-controlled treatment trial of depression in elderly physically ill patients.

OBJECTIVES: To determine the response of physically ill elderly depressed patients to treatment. DESIGN: Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine. MAIN OUTCOME MEASURE: Response rate as defined by the 17-item Hamilton Depression Rating Scale. RESULTS: Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02). CONCLUSIONS: The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important.

Aged↗

Treating children with early-onset conduct problems: a comparison of child and parent training interventions.

Families of 97 children with early-onset conduct problems, 4 to 8 years old, were randomly assigned to 1 of 4 conditions: a parent training treatment group (PT), a child training group (CT), a combined child and parent training group (CT + PT), or a waiting-list control group (CON). Posttreatment assessments indicated that all 3 treatment conditions had resulted in significant improvements in comparison with controls. Comparisons of the 3 treatment conditions indicated that CT and CT + PT children showed significant improvements in problem solving as well as conflict management skills, as measured by observations of their interactions with a best friend; differences among treatment conditions on these measures consistently favored the CT condition over the PT condition. As for parent and child behavior at home, PT and CT + PT parents and children had significantly more positive interactions, compared with CT parents and children. One-year follow-up assessments indicated that all the significant changes noted immediately posttreatment had been maintained over time. Moreover, child conduct problems at home had significantly lessened over time. Analyses of the clinical significance of the results suggested that the combined CT + PT condition produced the most significant improvements in child behavior at 1-year follow-up.

Analysis of Variance↗

Treatment of depression in the elderly: effect of physical illness on response.

OBJECTIVES: To determine the response to treatment of different subgroups within a sample of physically ill elderly depressed patients. DESIGN: Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine. MAIN OUTCOME MEASURE: Response rate as defined by the 17-item Hamilton Depression Rating Scale. RESULTS: Data were analysed in subgroups according to diagnosed physical problems and concomitant medication. A logistic regression analysis was performed to identify subgroups valid for separate analysis. Those reaching at least 5 weeks of treatment showed a significant improvement compared with the placebo group if they had serious life-threatening disease, cerebrovascular disease, were not demented, or were either on no analgesics or on analgesics stronger than paracetamol. CONCLUSION: While the response to treatment in these subgroups was encouraging, general physicians must not be led to believe that the answer to depression lies only in pharmacological intervention, just as the belief that the risk-benefit ratio of such treatment where indicated is too high must be discouraged.

Aged↗

A study of letters between general dental practitioners and consultant orthodontists.

A survey was undertaken involving 268 general dental practitioners and 13 orthodontic consultants to determine the content of letters passed between them. There was good agreement between the two sets of respondents as to the appropriate contents of a letter. The feature of a letter least valued by both dentists and consultants was a detailed description of the case, although 54% of consultants described cases at some length when replying to referrers. The information that GDPs valued most highly was a treatment plan, the date on which the patient was seen and the name of the clinician involved, a short case description and the length of time before treatment would being if the patient was accepted for specialist treatment.

Communication↗

Everyday memory following traumatic brain injury.

Residual memory deficits may represent a problem to the everyday functioning of a large number of people, including those who have sustained traumatic brain injury (TBI). The present exploratory study sought to investigate the interrelationships between subjective memory reports, performance on traditional memory tests, and performance on tests of prospective memory. These interrelationships were contrasted between a group of 24 adults who had sustained TBI and a group of 24 matched control subjects. Prospective memory was hypothesized to be indicative of everyday memory functioning. The results provided preliminary evidence that prospective memory tests are sensitive to TBI-related neurological impairment and, in comparison to traditional tests, may be better indicators of functional memory capacity. This pattern was particularly true for control subjects, possibly because TBI subjects had difficulties in evaluating their memory functioning.

Activities of Daily Living↗

Simple in vitro translation assay to analyze inhibitors of rhinovirus proteases.

We have developed a simple in vitro translation method to analyze compounds that inhibit the rhinovirus 3C protease in peptide substrate assays but demonstrate no antiviral activity. This complementary assay, which provides both qualitative and quantitative results, detects the inhibition of the 3CD protease in the native polyprotein form.

3C Viral Proteases↗

Immediate effects of mainstreamed settings on the social interactions and social integration of preschool children.

The immediate effects of mainstreamed and specialized settings on the peer interactions of preschool children with and without developmental delays were examined. Mainstreamed and specialized playgroups were established involving unacquainted peers and using a methodology that ensured appropriate matching of child and family characteristics. For each 2-week playgroup, the social and play interactions of each child were observed during a designated free-play period. Peer sociometric ratings also were obtained. Results indicated higher levels of peer interactions in mainstreamed settings for both typically developing children and children with developmental delays. The immediate impact of mainstreamed settings appeared to be attributed to the social demands and higher interaction levels of the former group. Children with developmental delays were not fully accepted nor totally socially integrated based on sociometric measures and behavioral indices of peer preferences. Implications of these findings for developing intervention programs to maximize children's peer-related social competence was discussed.

Child, Preschool↗