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Biomedical subjects

K Forrest

Publications and source records attributed to K Forrest.

At least 19 recordsLinked to original sources
PubMed2004

Systematic review: is ingestion of paracetamol or non-steroidal anti-inflammatory drugs associated with exacerbations of inflammatory bowel disease?

AIM: To examine the published evidence on the association between paracetamol or non-steroidal anti-inflammatory drugs and relapse in inflammatory bowel disease. METHODS: Medline searches were performed till June 2004 and Embase till April 2003. Abstracts published in Gut and Gastroenterology from 1999 to 2004 were hand-searched. Twenty-nine relevant abstracts and papers were identified. RESULTS: Twenty-two patients with relapse of inflammatory bowel disease following exposure to non-steroidal anti-inflammatory drugs have been described in case-reports. Four patients were re-exposed to non-steroidal anti-inflammatory drugs and relapsed again. Two had relapsed after taking a cyclo-oxygenase 2 inhibitor. One study described increased inflammatory activity and clinical relapse in some patients after challenge with naproxen or nabumetone. Fifteen epidemiological studies were identified. All had small sample sizes and many had methodological problems. Six studies found evidence for an association between non-steroidal anti-inflammatory drug use and relapse of inflammatory bowel disease, but the association was significant in only two. Three studies suggested a relationship between paracetamol use and exacerbations of inflammatory bowel disease. CONCLUSIONS: Non-steroidal anti-inflammatory drugs may precipitate a relapse in some patients with inflammatory bowel disease. This may be an idiosyncratic reaction. The published evidence does not support the view that non-steroidal anti-inflammatory drugs are important in inducing relapse of inflammatory bowel disease. There is weak evidence that paracetamol may be more important.

Acetaminophen↗
PubMed2003

To tell or not to tell: barriers and facilitators in family communication about genetic risk.

Communication about genetic risk in families is an important issue for genetic counsellors. The objective of this study was to explore the barriers and facilitators in family communication about genetic risk. Semi-structured interviews were undertaken with patients in the Northeast of Scotland who had attended genetic counselling for risk of hereditary breast and ovarian cancer and Huntington's disease, and with some spouses/partners. The interviews confirmed that the issue of disclosure was a problem for some, and that there were generic communication issues common to both groups. Telling family members about genetic risk was generally seen as a family responsibility and family structures, dynamics and 'rules' influenced disclosure decisions. A sense of responsibility towards younger generations was also important. The level of certainty felt by a person in relation to his or her own risk estimate also influenced what he or she could tell other family members. Communication within a family about genetic risk is a complex issue and is influenced by both pre-existing familial and cultural factors and individuals' responses to risk information. If genetic counsellors understood how these factors operate in individual families they might be able to identify effective strategies to promote considered decisions and prevent unnecessary emotional distress.

Adult↗
PubMed2003

Activated eosinophils upregulate the metastasis suppressor molecule E-cadherin on prostate tumor cells.

Cell adhesion molecules (CAMs) play an important role in cancer metastasis by facilitating attachment to vascular endothelia, invasion and spread into secondary tissue sites. We have shown that activated eosinophils (EosA) inhibited the growth of prostate cancer (Pca) cells in vitro. In the present study, we examined the ability of EosA 24 hr conditioned supernatants (EosAcs) to modulate the expression of ICAM-1, VCAM-1, ELAM-1, E-cadherin and N-cadherin expression on human Pca cell lines, Du-145 and PC-3 by flow cytometry. TNF-alpha, IL-10 and IL-12 were also evaluated. ICAM-1, expressed on PC-3 and DU 145 cells, was enhanced by TNF-alpha and IL-10. ELAM-1 was present on DU 145 cells but absent on PC-3. TNF-alpha and IL-10 enhanced ELAM-1 on DU 145, but EosA 24 hr supematants failed to do so. All three cytokines, namely IL-10, IL-12 and TNF-alpha-induced ELAM-1 on PC-3 tumor cells. Although VCAM-1 was absent on DU 145 and PC-3 cells, it was expressed on DU-145 cells after exposure to EosA: tumor cell co-cultures, and was expressed on PC-3 following exposure to IL-10 and IL-12. N-cadherin and E-cadherin were both expressed on DU-145. While N-cadherin was expressed on PC-3 cells, E-cadherin was not. N-cadherin was enhanced on DU-145 and PC-3 cells following exposure to EosA co-culture and upregulated on PC-3 by IL-10 and EosA 24 hr supernatants, but decreased by IL-12. E-cadherin was up-regulated on DU 145 cells following co-culture with EosA and was induced on PC-3 by IL-10 and IL-12, but not by EosA co-culture and 24 hr supematants. In conclusion, inflammatory and non-inflammatory cytokines modulate CAM expression on Pca cells; EosA and EosA 24 hr supernatants also exerted modulatory activity of CAM expression. Most significantly, the metastasis suppressor molecule, E-cadherin was enhanced on DU 145 cells by EosA and induced on PC-3 by IL-10 and IL-12 both of which are produced by EosA. This suggests potential use of these cytokines in immunotherapeutic strategies for prostate cancer and its metastasis.

Cadherins↗
PubMed2003

Eosinophils in a tri-cell multicellular tumor spheroid (MTS)/endothelium complex.

Eosinophils have been found in infiltrates of many different cancers. It is still unclear as to whether they are passive bystanders in the cellular milieu or active cellular agents in host responses. Thus their harmful or helpful nature remains equivocal. We have developed an in vitro tri-cell model of eosinophils, MCF-7 breast tumor cell spheroids and HUVEC endothelial cells to examine the binding and association of eosinophils with both the tumor and the endothelia and the ensuing action of the tumor. Eosinophils bound very rapidly to the tumor spheroid and remained tightly bound throughout the 24 hr culture period. Histological staining of the tri-cell complex revealed highly granulated eosinophils as well as large amounts of degranulated protein diffused throughout the spheroid. IL-5 treatment of eosinophil: MTS complexes resulted in destruction of the tumor cells, particularly those which had grown out from the spheroid onto the endothelial cells. Eosinophils, pretreated with IL-5 before interaction with the tumor or endothelial cells, bound aggressively to the endothelial cells, thereby preventing tumor attachment. This eosinophil tri-cell tumor model system mimics clinical observations with regards to binding to epithelial and endothelial cells, dispersal of granular proteins throughout the tumor and also tumor destruction. Because it closely mirrors in vivo cellular interactions, it allows one to study more closely the mechanism(s) of eosinophil killing, the modulation of eosinophil activity and the testing of therapeutic interventions. The accommodation of the model to tumor invasion, using metastatic tumor cells and extracellular matrices such as matrigel, will help to elucidate a role for eosinophils (and their mediators) in cancer invasion and metastasis.

Breast Neoplasms↗
PubMed2001

Interstitial nephritis, hepatic failure, and systemic eosinophilia after minocycline treatment.

This report describes a 15-year-old white boy who presented with fever, back pain, a disseminated exanthematous rash, renal failure, and hepatopathy 3 weeks after the initiation of oral minocycline therapy for facial acne. Marked peripheral and urine eosinophilia were noted. A bone marrow aspiration showed more than 50% eosinophils without any evidence of malignancy, and a simultaneous kidney biopsy showed acute interstitial nephritis (AIN). The patient's symptoms and laboratory findings improved after high-dose steroid therapy was initiated, worsened when it was withheld, and improved again after it was reinitiated in view of the biopsy findings. The patient recovered completely, and steroids were tapered to discontinuation over 3 months. Over a year later, the patient's peripheral blood mononuclear cells (PBMCs) were cultured for 2 weeks in the presence or absence of minocycline ex vivo, and minocycline was found to induce the emergence of CD4(+) cells after 1 week in culture. In conclusion, this article shows for the first time several new aspects of minocycline-induced morbidity: renal and hepatic failure can occur together, and AIN and elevated blood eosinophil counts can be accompanied by marked bone marrow eosinophilia, suggesting a systemic allergic response as the underlying pathomechanism. Furthermore, the initial phase of such a response appears to involve CD4(+) T cells detectable ex vivo. Lastly, high-dose treatment with corticosteroids appears to be beneficial in this setting.

Acne Vulgaris↗
PubMed2000

Daclizumab (Zenapax) inhibits early interleukin-2 receptor signal transduction events.

Daclizumab, a humanized antibody against the interleukin-2 (IL-2) receptor (R) alpha-chain, is a promising new immunosuppressant in transplantation. As its exact mechanism of action has remained unclear, we examined its short-term effects on primary human T lymphocytes expressing the high-affinity IL-2R. Daclizumab exposure for 20 min neither affected T cell viability nor their surface expression of the IL-2R alpha-, beta-, or gamma-chains. However, after IL-2 stimulation (200 U/ml, 20 min), immunoblots of cell lysates demonstrated attenuation of the IL-2-induced tyrosine phosphorylation of 65-75 kDa proteins by Daclizumab, but not by isotype controls. Since this is the molecular weight of the IL-2R beta- and gamma-chains, which are both tyrosine-phosphorylated by IL-2, we next examined the effect of Daclizumab on their IL-2-induced tyrosine phosphorylation. In immunoblots of IL-2R beta- and gamma-chain-immunoprecipitates the tyrosine phosphorylation of both chains by IL-2, but not by IL-15, was attenuated in the presence of Daclizumab. Furthermore, co-immunoprecipitation experiments showed that Daclizumab inhibited the IL-2-induced association of these chains, a prerequisite for their mutual tyrosine phosphorylation. Lastly, we demonstrated that Daclizumab inhibits the receptor-downstream induction of the IL-2-activated DNA-binding protein STAT5 in gel shift assays. We conclude that Daclizumab directly and specifically interferes with IL-2 signaling at the receptor level by inhibiting the association and subsequent phosphorylation of the IL-2R beta- and gamma-chains induced by ligand binding. Under our experimental conditions, Daclizumab had no effects on cell viability, and it did not modulate the surface expression of the IL-2R alpha-, beta-, or gamma-chains.

Animals↗
PubMed1999

Feature analysis of segmental errors in children with phonological disorders.

There has been a longstanding controversy about the existence, nature, and differentiation of developmental apraxia of speech (DAS), leading to numerous investigations of characteristics that define this articulatory disorder. An analysis of substitutions relative to target sounds led Thoonen, Maassen, Gabreëls, and Schreuder (1994) to conclude that children with DAS show a pattern of feature retention in their error productions that contrasted with that of children with normal articulation. This pattern, in which place of articulation was retained in the substituted sound less frequently than manner of production or voicing, was considered by Thoonen et al. to be of diagnostic significance. The current research re-examines this claim by comparing the retention patterns obtained by Thoonen et al. for children suspected of having DAS to patterns for children suspected of having a phonological disorder. An examination of substitutions used by 20 children who were diagnosed with and treated for phonological disorders demonstrated the same pattern of feature retention that was described for children with DAS. The results of this study showed that voicing is maintained most frequently; manner of production is the next most retained feature; and place of articulation is the feature that is retained least often when a substitute is used for a sound that isn't produced correctly. In a second analysis, this pattern of feature retention was compared to children's phonological knowledge as indexed by percent correct underlying representation (PCUR). Contrary to the findings of Thoonen et al., however, the present work found an inverse relationship between retention of place and phonological knowledge. Children with greater phonological knowledge retained place less often than children with more limited phonetic inventories. These patterns of feature retention may be representative of specific development sequences that occur during phonological acquisition.

Articulation Disorders↗
PubMed1999

The association between osteopenia and periodontal attachment loss in older women.

BACKGROUND: Recent research suggests that osteopenia may be a predisposing factor for periodontal tissue destruction. If so, then a relationship should exist between measures of systemic bone mineral density and periodontal tissue destruction. The purpose of the present cross-sectional study was to evaluate the association between systemic bone mineral density and the clinical signs of periodontal tissue destruction in a large population of elderly dentate women. METHODS: A total of 292 dentate women (average age 75.5 years) were randomly selected for a cross-sectional periodontal substudy from participants at the Pittsburgh Field Center of the Study of Osteoporotic Fractures (SOF), a prospective study of a cohort of elderly women (age > or =65 years at baseline) to determine risk factors for fractures. Bone mineral density (BMD) was measured using single photon absorptiometry (radius, calcaneus) and dual energy x-ray absorptiometry (hip, spine). Oral health examinations, including periodontal probings and an assessment of bleeding on probing, were made using an NIDR probe at 3 buccal sites of all teeth. Multiple regression models were used to assess the association between bone mineral density and measures of periodontal disease status while controlling for potential confounders. Periodontal status variables examined included: average loss of periodontal attachment (LOA); number of sites with at least 4 mm LOA; number of sites with at least 6 mm LOA; number of sites with bleeding on probing; and deepest probing depth per person. RESULTS: This study found no statistically significant association between the 5 indicators of periodontal disease and measures of systemic BMD at 8 anatomic sites after controlling for age, smoking, and number of remaining natural teeth. Some suggestive findings support a weak association between generalized osteopenia and periodontal disease. CONCLUSIONS: Systemic osteopenia is, at best, only a weak risk factor for periodontal disease in older non-black women.

Absorptiometry, Photon↗
PubMed1995

Dynamic aspects of lower lip movement in parkinsonian and neurologically normal geriatric speakers' production of stress.

Lower lip+jaw movement was evaluated for parkinsonian dysarthric and age-matched, neurologically normal speakers during the production of alternating stress contrasts. Discrete measures of movement, including displacement amplitude, peak velocity, the relation of amplitude to peak velocity, and movement durations were compared across groups for stressed and unstressed syllables. Additionally, quantitative (parameter c and the ratio of acceleration to deceleration) and qualitative indices of dynamic characteristics of velocity profiles for lower lip+jaw opening and closing gestures were compared across the subject groups. Within the dysarthric group, the relation between each discrete and dynamic kinematic parameter and the perceived severity of the dysarthria was investigated. The discrete measures confirmed previous findings of reduced displacement and peak velocity for the parkinsonian speakers during opening and closing gestures for both the stressed and unstressed syllables. However, the relation between amplitude and velocity did not differ for the two subject groups for any gesture. Movement durations were equivalent for the two groups during the production of opening gestures, but were significantly shorter for the parkinsonian speakers during closing gestures. Quantitative indices of the velocity profiles also failed to differentiate between the subject groups or between dysarthric speakers as a function of severity. By contrast, the qualitative descriptions of the velocity profiles showed between-speaker differences that were more pronounced for subjects with more severe dysarthria. These qualitative differences were evident in opening gestures toward an unstressed vowel, only.

Aged↗
PubMed1990

Statistical comparison of movement amplitudes from groupings of normal geriatric speakers.

An implicit assumption of many studies of articulatory kinematics is that all normal speakers are equivalent, at least in a statistical sense. The present report investigated this assumption by performing post hoc analyses on random groups of 8 normal, geriatric males. Results of these analyses suggest that, at least for the geriatric population, small numbers of subjects may not represent the parent population adequately, especially when the unit of statistical analysis is the individual trial. These findings have implications for the types of generalizations that can be made from studies with small samples and suggest the need for more comprehensive investigations of speech kinematics.

Aged↗
PubMed1990

Readability of commercial versus generic health instructions for condoms.

Despite the fact that condoms are increasingly recommended for the prevention of acquired immune deficiency syndrome (AIDS) and other sexually transmitted diseases (STDs) and have long been used as a barrier method of contraception, little is known about the readability of the range of materials that have been written exclusively for consumers on how to use a condom. The authors described and compared the reading comprehension levels of condom patient package inserts (PPIs) prepared commercially and those generic instructions (GIs) prepared by health care providers. Fifteen sets of PPIs and 30 sets of GIs were analyzed using six standard readability formulas (Fry, Fog, Dale-Chall, Flesch, Flesch-Kincaid, SMOG). Readability levels of the instructions ranged from grade 6.3 to 13.7. The PPIs required a significantly higher grade level for comprehension (mean 10.32) than the GIs (mean 8.69). This study suggests that instructions prepared by both sources may require a reading level above that of many consumers who need information on how to use a condom.

Contraceptive Devices, Male↗
PubMed1990

Readability of commercial and generic contraceptive instructions.

This study describes the readability levels of written instructions for methods of contraception. Materials studied include patient package inserts (PPIs) from commercial manufacturers and generic instructions (GIs) written by staff members in selected health agencies in the community and by health information publishers. Written materials were analyzed using Dale-Chall, Fry, Fog, Flesh, Flesch-Kincaid and SMOG formulas for readability. Readability levels ranged from elementary school (grade 5.5) to college (grade 13.6). Required comprehension levels of the PPIs were higher than those of the GIs for three of the four groups of contraceptives studied (diaphragms, pills, condoms).

Contraceptive Devices↗
PubMed1990

Listeners' familiarity and perception of an idiosyncratic phonologic pattern.

Idiosyncratic production of [l] for target /j/ (for example, production of the word "less" for "yes") was observed in a phonologically impaired preschooler. Recordings of his apparently homonymous productions of minimal pairs contrasting /j/ and /l/ were presented in random order to the child's mother and to five adult listeners who were unfamiliar with the child. No difference was seen across the listeners in their ability to identify target /l/ words. The child's mother, however, correctly identified /j/ targets more frequently than did unfamiliar listeners suggesting that familiarity enhances one's ability to decode idiosyncratic phonologic error patterns.

Articulation Disorders↗
PubMed1989

A study of the vaginal contraceptive sponge used with and without the fertility awareness method.

The actual effectiveness rates of natural and barrier methods of family planning are lower than the theoretical ones. If couples accurately defined the limits of the fertile phase and used barriers at that time, then actual effectiveness might increase. A randomized, controlled clinical trial was initiated to determine the effectiveness of the contraceptive sponge used only during the fertile time and to compare this with sponge use at every intercourse. Recruitment problems and discontinuation forced the early termination of this study, but qualitative information about compliance and acceptability was collected. Common sponge problems were reported as were misuses of the sponge, but problems and misuse were not related. Determination of the fertile phase was reportedly easy, but complaints of and discontinuation for inconvenience occurred. For unplanned pregnancies, contraceptive behaviors around the time of conception are presented.

Adolescent↗
PubMed1989

Evaluation of the clinical performance of three triphasic oral contraceptives: a multicenter, randomized comparative trial.

Three hundred thirteen women participated in an open, multicenter comparison of the incidence of intermenstrual bleeding (breakthrough bleeding and or spotting) associated with the use of three triphasic oral contraceptives. Triphasil (n = 107), containing levonorgestrel and ethinyl estradiol, and Ortho-Novum 7/7/7 (n = 97) and Tri-Norinyl (n = 109), both of which contain norethindrone and ethinyl estradiol, were administered over four cycles for a total of 1141 cycles. The total incidence of intermenstrual bleeding was significantly lower with Triphasil (17.2%) than with Ortho-Novum 7/7/7 (39.5%) or Tri-Norinyl (49.0%). The pattern remained the same when findings were analyzed cycle by cycle and for breakthrough bleeding and spotting separately. The incidence of other side effects was comparable for all regimens. Results of this study demonstrate superior cycle control with Triphasil compared with Ortho-Novum 7/7/7 and Tri-Norinyl during the first four cycles of use.

Adolescent↗
PubMed1989

Kinematic, acoustic, and perceptual analyses of connected speech produced by parkinsonian and normal geriatric adults.

Acoustic and kinematic analyses, as well as perceptual evaluation, were conducted on the speech of Parkinsonian and normal geriatric adults. As a group, the Parkinsonian speakers had very limited jaw movement compared to the normal geriatrics. For opening gestures, jaw displacements and velocities produced by the Parkinsonian subjects were about half those produced by the normal geriatrics. Lower lip movement amplitude and velocity also were reduced for the Parkinsonian speakers relative to the normal geriatrics, but the magnitude of the reduction was not as great as that seen in the jaw. Lower lip closing velocities expressed as a function of movement amplitude were greater for the Parkinsonian speakers than for the normal geriatrics. This increased velocity of lower lip movement may reflect a difference in the control of lip elevation for the Parkinsonian speakers, an effect that increased with the severity of dysarthria. Acoustically, the Parkinsonian subjects had reduced durations of vocalic segments, reduced formant transitions, and increased voice onset time compared to the normal geriatrics. These effects were greater for the more severe, compared to the milder, dysarthrics and were most apparent in the more complex, vocalic gestures.

Acoustic Stimulation↗