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Biomedical subjects

K Harris

Publications and source records attributed to K Harris.

At least 73 records · Page 4Linked to original sources

2-Phenyl-4-(aminomethyl)imidazoles as potential antipsychotic agents. Synthesis and dopamine D2 receptor binding.

A series of 2-phenyl-4-(aminomethyl)imidazoles were designed as conformationally restricted analogs of the dopamine D2 selective benzamide antipsychotics. The title compounds were synthesized and tested for blockade of [3H]YM-09151 binding in cloned African green monkey dopamine D2 receptor preparations. The binding affinity data thus obtained were compared against that of the benzamides and a previously described series of 2-phenyl-5-(aminomethyl)-pyrroles.

Animals↗

The transdermal nicotine patch: results of a randomised placebo-controlled trial.

OBJECTIVES: To evaluate the efficacy of the transdermal nicotine patch as an aid to smoking cessation when used as an adjunct to a cognitive-behavioural group intervention and to assess the effectiveness of the patch in ameliorating withdrawal symptoms. DESIGN AND SETTING: Double-blind placebo-controlled randomised trial with six months' follow-up of those who returned to the hospital-based outpatients smoking cessation clinic. SUBJECTS: Three hundred and thirteen smokers recruited from the local community. Mean age was 42 years, 48% were male, mean cigarette consumption was 29 per day and mean duration of smoking was 24 years. INTERVENTION: Cognitive-behavioural intervention delivered in a group context, two hours once a week over five weeks, self-help manual, and 24-hour daily nicotine patch treatment for 10 weeks. MAIN OUTCOME MEASURES: Point prevalence abstinence at three and six months, and sustained cessation from end of treatment to six months, with biochemical validation (expired carbon monoxide). We examined the effectiveness of the nicotine patch in ameliorating specific withdrawal symptoms by self-report of degree of severity. RESULTS: The active nicotine patch resulted in significantly higher biochemically confirmed abstinence rates when compared with placebo at three months (48% v. 21%) and at six months (33% v. 14%). Six-months' continuous abstinence rates were also significantly higher among the active nicotine group (25%) compared with placebo (12%). The most common adverse events among active patch users were sleep disturbance and local skin irritation. The nicotine patch reduced the severity of some withdrawal symptoms. A low level of dependence was the strongest predictor of three and six months' abstinence. CONCLUSIONS: The transdermal nicotine patch is effective when used as an adjunct to a group cognitive-behavioural intervention and it provides relief from withdrawal symptoms associated with nicotine dependence.

Administration, Cutaneous↗

Mycoplasma agassizii causes upper respiratory tract disease in the desert tortoise.

The desert tortoise is listed by the United States government as a threatened species in part of its range. A major contributing factor in the decline of this animal has been the presence of an upper respiratory tract disease (URTD) which is characterized by a chronic disease which eventually leads to severe occlusion of the nares with viscous exudate and destruction of the respiratory epithelium. Electron microscopy of infected tissues demonstrated the presence of a mycoplasma-like organism attached to the respiratory surfaces. The mycoplasma was isolated and designated as a new species, with the proposed name Mycoplasma agassizii. The current study was designed to fulfill Koch's postulates and determine if M. agassizii was the etiologic agent of URTD. Clinically healthy animals with known antibody status were infused intranasally with pooled exudate (n = 8) from ill donor animals, with M. agassizii alone (n = 9) or in combination with Pasteurella testudinis (n = 8), with P. testudinis alone (n = 9), or with sterile broth (n = 12). The pooled exudate was culture positive for M. agassizii. Tortoises which received exudate or M. agassizii alone or in conjunction with P. testudinis were significantly more likely to develop clinical disease (P < 0.0004) than animals which received P. testudinis alone or the broth controls. Tortoises demonstrated a strong immune response to M. agassizii, and seroconversion was seen in all groups with clinical disease. M. agassizii was isolated from the upper respiratory tracts of clinically ill animals up to 6 months postinfection. On the basis of the results of these transmission studies, we conclude that M. agassizii is an etiologic agent of URTD in the desert tortoise.

Animals↗

Is breast preservation possible in women with large, locally advanced breast cancers?

Breast conservation therapy is an accepted treatment option for early stage breast carcinoma, but is rarely considered appropriate for locally advanced nonmetastatic lesions. Mastectomy specimens of 46/50 patients treated at the Ochsner Clinic and the Mallinckrodt Institute of Radiology with neoadjuvant chemotherapy prior to mastectomy +/- irradiation were evaluated by a single pathologist to assess tumor response to chemotherapy. Forty percent of this group would potentially have been eligible for breast conservation therapy, using a residual tumor size of < or = 4 cm with negative surgical margins as the criteria. Patients most likely to qualify for breast conservation therapy were those with T3N0-1 lesions (67%). Least likely were patients with skin involvement at diagnosis 4/33 (12%). Tumors with an extensive intraductal component at biopsy often had residual islands of intraductal carcinoma occupying the original tumor volume, even when the invasive component was absent or much reduced. A prospective trial will be required to determine whether or not acceptable local control rates can be obtained after breast conservation therapy for that subset of patients with a favorable response to induction chemotherapy.

Adult↗

Demonstration by S-100 protein staining of increased numbers of nerves in the papillary dermis of patients with prurigo nodularis.

BACKGROUND: We hypothesized that hyperplasia of papillary dermal nerves was a constant feature of prurigo nodularis. OBJECTIVE: We tested this hypothesis by examining sections from 25 cases of prurigo nodularis, 25 cases of skin lesions characterized by epidermal hyperplasia without clinical pruritus, and 22 cases of clinically pruritic dermatoses with variable degrees of epidermal response for the presence of papillary dermal nerves. METHODS: We used a standard immunohistochemical assay with an antibody to S-100 protein as a means of identification of nerves. RESULTS: In 24 of 25 cases of prurigo nodularis, papillary dermal nerves were identified by immunostaining. Cutaneous nerves were present in 1 of 22 cases of epidermal hyperplasia with pruritus and were absent in the papillary dermis in nonpruritic cases. CONCLUSION: We conclude that hypertrophy of cutaneous papillary dermal nerves is a relatively constant feature of prurigo nodularis. The presence of papillary dermal nerves suggests a neurocutaneous component in the pathogenesis of prurigo nodularis.

Humans↗

Reassessment of the temporal patterns of bronchial obstruction after exposure to occupational sensitizing agents.

Typical asthmatic reactions after exposure to common or occupational allergens have been classified as isolated immediate, early late, late, and dual (Pepys and Hutchcroft, 1975). Atypical reactions can also occur, but their temporal behavior and frequency are unknown. We analyzed 69 bronchospastic reactions after exposure to three types of occupational sensitizers in the laboratory: isocyanates, western red cedar, and IgE sensitizing agents. Graphs of the reactions were presented to three observers in a blind, randomized way. Reactions were defined as follows: (1) typical patterns, that is, isolated immediate, early late, late, and dual, as put forward by Pepys and Hutchcroft, and (2) atypical patterns including progressive (onset, during, or minutes after exposure, progressing to a maximum reaction 5 to 6 hours later) and square waved (similar to a dual reaction but with only partial recovery [less than 10%] between the immediate and late falls in FEV1). Some curves were also analyzed by polynomial regression. The three observers agreed in 59/69 cases (86%), and a consensus was reached after discussion for the remaining subjects. Fifteen of 63 (22%) reactions were atypical. IgE-mediated reactions and reactions to red cedar were, respectively, mainly of the immediate and late types. The distribution of reactions to isocyanates, however, was significantly different (chi-square, 6.1; p = 0.01), the "progressive" pattern occurring in 7/23 instances (30%). There was a satisfactory concordance between visual assessment and polynomial fit analysis in distinguishing dual from square-waved reactions. We conclude that isocyanates frequently cause atypical progressive bronchospastic reactions that are rarely observed after exposure to IgE agents and western red cedar.

Adult↗

Relations between prosodic variables and communicative functions.

Three children were observed interacting with their mothers at three different times: before the onset of single words, when vocabulary consisted of 10 words, and when vocabulary consisted of 50 words. Relations between communicative functions and acoustic analyses of prosodic variables (i.e. rise vs. nonrise of terminal contours) were studied. Considerable variability was found among the children in the number of rises produced overall and those produced for any function. Each child's use of rise was fairly constant over time and rises were produced relatively more frequently than nonrises with functions requiring a response from the listener. Factors affecting similarities and differences are discussed.

Child Language↗

Inability to express fimbriae results in impaired ability of Haemophilus influenzae b to colonize the nasopharynx.

We cloned into the structural fimbrial subunit gene from a fimbriated Haemophilus influenzae b a 1.5-kb kanamycin resistance gene. The resultant strain (RKAW5) was tested by Southern analysis, hemagglutination, and electron-micrographic examination to confirm gene inactivation. In comparison with the parent, RKAW5 exhibited a significant decrease in adherence to human buccal epithelial cells and in nasal colonization of yearling rhesus monkeys.

Animals↗

Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients.

Identifying lower respiratory pathogens in young, non expectorating cystic fibrosis (CF) patients has been problematic. Bronchial secretions are difficult to obtain, and little is known about lower airway flora in these patients. We collected simultaneous bronchial and oropharyngeal specimens in 43 CF patients in optimal respiratory status, including both expectorating (17) and nonexpectorating (26) patients, to determine the predictive value of oropharyngeal cultures for identifying lower airway pathogens. An additional goal was to characterize the lower respiratory flora of these patients. Predictive values were defined as the proportion of oropharyngeal culture results that accurately reflected the results of bronchial cultures. Predictive values of positive oropharyngeal cultures in nonexpectorating patients were 83% (95% confidence interval 36 to 100%) for Pseudomonas aeruginosa and 91% (59 to 100%) for Staphylococcus aureus. Predictive values of negative oropharyngeal cultures were lower: 70% (48 to 86%) for R aeruginosa and 80% (52 to 96%) for S. aureus. A relatively high proportion of nonexpectorating CF patients less than 10 yr old had R aerusginosa (11 of 24, 46%) or Klebsiella species (5 of 24, 21%) in their lower airways. The isolation of Klebsiella was associated with younger age (p = 0.03) and recent administration of antistaphylococcal antibiotics (p = 0.05). Our results suggest that oropharyngeal cultures yielding R aeruginosa or S. aureus are highly predictive, but such cultures lacking these organisms do not rule out the presence of these pathogens in the lower airways of CF patients.

Bacterial Infections↗

Bone scans and the timing of treatment for condylar hyperplasia.

Bone scintiscans comparing the uptake of technetium 99 in the normal and affected condyles of 10 patients with unilateral condylar hyperplasia were recorded at or after the time when overall growth had ceased. The scans of 6 patients demonstrated persisting increased growth activity at this time. In 2 of these cases where the abnormal condyles showed uptakes of 240% and 170% with respect to the normal side, the nature and timing of treatment were changed when the results of the scans were known.

Adolescent↗