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Biomedical subjects

P Kay

Publications and source records attributed to P Kay.

At least 19 recordsLinked to original sources

Further evidence that Whorfian effects are stronger in the right visual field than the left.

The Whorf hypothesis holds that differences between languages induce differences in perception and/or cognition in their speakers. Much of the experimental work pursuing this idea has focused on the domain of color and has centered on the issue of whether linguistically coded color categories influence color discrimination. A new perspective has been cast on the debate by recent results that suggest that language influences color discrimination strongly in the right visual field but not in the left visual field (LVF). This asymmetry is likely related to the contralateral projection of visual fields to cerebral hemispheres and the specialization of the left hemisphere for language. The current study presents three independent experiments that replicate and extend these earlier results by using different tasks and testing across different color category boundaries. Our results differ in one respect: although we find that Whorfian effects on color are stronger for stimuli in the right visual field than in the LVF, we find that there are significant category effects in the LVF as well. The origin of the significant category effect in the LVF is considered, and two factors that might account for the pattern of results are proposed.

Adult↗

A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity.

Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene. In this study, we demonstrate that a soluble ectodomain of LRIG1, containing only the LRRs, inhibits ligand-independent epidermal growth factor receptor (EGFR) activation and causes growth inhibition of A431, HeLa and MDA-468 carcinoma cells. In contrast, cells that do not express detectable levels of EGFR fail to respond to soluble LRIG1. However, when a functional EGFR gene is introduced in these cells, they become growth-inhibited by soluble LRIG1 protein. Furthermore, we demonstrate the existence of high-affinity (K(d)=10 nM) binding sites on the A431 cells that can be competitively displaced (up to 75%) by molar excess of EGF. Even more powerful effects are obtained with a chimeric proteoglycan harboring the N-terminus of decorin, substituted with a single glycosaminoglycan chain, fused to the LRIG1 ectodomain. Both proteins also inhibit ligand-dependent activation of the EGFR and extracellular signal-regulated protein kinase 1/2 signaling in a rapid and dose-dependent manner. These results suggest a novel mechanism of action evoked by a soluble ectodomain of LRIG1 protein that could modulate EGFR signaling and its growth-promoting activity. Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival.

Amino Acid Sequence↗

Veterinary medicines in the environment.

The impact of veterinary medicines on the environment will depend on a number of factors including physicochemical properties, amount used and method of administration, treatment type and dose, animal husbandry practices, manure storage and handling practices, metabolism within the animal, and degradation rates in manure and slurry. Once released to the environment, other factors such as soil type, climate, and ecotoxicity also determine the environmental impact of the compound. The importance of individual routes into the environment for different types of veterinary medicines varies according to the type of treatment and livestock category. Treatments used in aquaculture have a high potential to reach the aquatic environment. The main routes of entry to the terrestrial environment are from the use of veterinary medicines in intensively reared livestock, via the application of slurry and manure to land, and by the use of veterinary medicines in pasture-reared animals where pharmaceutical residues are excreted directly into the environment. Veterinary medicines applied to land via spreading of slurry may also enter the aquatic environment indirectly via surface runoff or leaching to groundwater. It is likely that topical treatments have greater potential to be released to the environment than treatments administered orally or by injection. Inputs from the manufacturing process, companion animal treatments, and disposal are likely to be minimal in comparison. Monitoring studies demonstrate that veterinary medicines do enter the environment, with sheep dip chemicals, antibiotics, sealice treatments, and anthelmintics being measured in soils, groundwater, surface waters, sediment, or biota. Maximum concentrations vary across chemical classes, with very high concentrations being reported for the sheep dip chemicals. The degree to which veterinary medicines may adsorb to particulates varies widely. Partition coefficients (K(d)) range from low (0.61 L kg(-1)) to high (6000 L kg(-1)). The variation in partitioning for many of the compounds in different soils was significant (up to a factor of 30), but these differences could be not be explained by normalization to the organic carbon content of the soils. Thus, to arrive at a realistic assessment of the availability of veterinary medicines for transport through the soil and uptake into soil organisms, the K(oc) (which is used in many of the exposure models) may not be an appropriate measure. Transport of particle-associated substances from soil to surface waters has also been demonstrated. Veterinary medicines can persist in soils for days to years, and half-lives are influenced by a range of factors including temperature, pH, and the presence of manure. The persistence of major groups of veterinary medicines in soil, manure, slurry, and water varies across and within classes. Ecotoxicity data were available for a wide range of veterinary medicines. The acute and chronic effects of avermectins and sheep dip chemicals on aquatic organisms are well documented, and these substances are known to be toxic to many organisms at low concentrations (ng L(-1) to microg L(-1)). Concerns have also been raised about the possibility of indirect effects of these substances on predatory species (e.g., birds and bats). Data for other groups indicate that toxicity values are generally in the mg L(-1) range. For the antibiotics, toxicity is greater for certain species of algae and marine bacteria. Generally, toxicity values for antibacterial agents were significantly higher than reported environmental concentrations. However, because of a lack of appropriate toxicity data, it is difficult to assess the environmental significance of these observations with regard to subtle long-term effects.

Agriculture↗

Salvage revision total knee replacement using the Endo-Model rotating hinge prosthesis.

Inability to balance a knee in complex revision total knee replacement has led to the use of rotating hinged knee devices in these cases as a salvage procedure. We conducted a retrospective study of 50 patients receiving 51 Endo-Model rotating hinge prosthesis with an average follow-up of 4 years (range 2-6 years). Clinical and radiological results were reviewed at latest follow-up. Five patients died from unrelated causes. Reasons for revision were infection (23), aseptic loosening (23), implant failure (3), stiffness (1) and peri-prosthetic fracture (1). The average number of previous surgery from and including the primary arthroplasty was three (ranges 1-14). Seven patients required plastic surgery for soft tissue cover. There was notable improvement in the pain, stability, range of motion and mobility of the patients with an improvement in the Hospital for Special Surgery Score (35.9 to 72.17). Postoperatively, 11 (22%) had an excellent HSS grade, 22 (44%) good grade, 10 (19%) fair grade and 8 (15%) poor grade. A significant number of our patients had an extremely low preoperative HSS score, and for these patients, an improvement to a fair grade HSS score was a satisfactory and realistic outcome. Forty-four (86%) patients were satisfied with the outcome of the revision surgery, 3 (6%) noncommittal and 4 (8%) disappointed. Comparing revision for infection vs. aseptic loosening, 22 (95%) patients out of 23 were satisfied in the aseptic loosening group vs. 17 (74%) out of 23 were satisfied in the infected group. In selected complex cases, salvage revision surgery shows encouraging results in the short to medium term using the Endo-Model rotating hinge prosthesis. A knee score such as the Hospital for Special Surgery score (objective outcome) should be used in conjunction with a patient satisfaction questionnaire (subjective outcome) in assessing the clinical outcome of complex, salvage revision knee surgery. Revision for infected total knee replacement is less likely to produce a satisfactory outcome as compared to revision for aseptic loosening.

Adult↗

The use of knee splints after total knee replacements.

The aim of this randomised prospective study was to establish whether the use of knee splints following total knee replacement is necessary. The study included 81 patients undergoing total knee replacement who were randomised into a 'splint' and a 'no splint' group post-operatively. The following parameters were recorded: The range of movement pre-operatively, 5 days post-operatively and 6 weeks post-operatively; the length of time to straight leg raise; the blood drained from the wound; and the amount of post-operative analgesia required. We found that patients in the 'no splint' group achieved significantly greater flexion at 5 days and 6 weeks post-operatively but drained significantly more blood from the wound. Transfusion requirements were similar in the two groups. There was no other significant difference in the parameters measured between the two groups. In conclusion we found no evidence to advocate the use of knee splints following total knee arthroplasty.

Aged↗

Disability and mental health of patients waiting for total hip replacement.

We performed a cross sectional study to examine the relationship between physical function and mental health of patients waiting for total hip replacement surgery, and the relationship between physical and social function and mental health to time spent waiting for surgery. We found that, in addition to the expected poor hip function, limited mobility and pain, one-quarter of the patients had clinically significant mood disorders and another quarter were in the borderline range. No association was found between severity of mental disorder and assessment of hip function. The patients had been waiting for 1-26 months (median 6 months) for surgery: yet those waiting longest were no worse on any of the outcome measures and their mental health was better. We conclude that mental disorders are common in patients waiting for hip replacements, are not directly related to hip function and their origins are unknown, but they require clinical assessment and treatment. There is no evidence that physical or social function or mental health are worse in those waiting longer for hip replacement surgery. Even so, these patients are severely disabled and some have to wait too long.

Adult↗

Oral antibodies to human papillomavirus type 16 in women with cervical neoplasia.

This study investigated the relationship between human papillomavirus type 16 (HPV-16) antibodies detected in oral fluid from women with cervical neoplasia, their HPV-16 antibody seroprevalence, and their cervical HPV-16 DNA presence. Cervical HPV-16 DNA was detected by polymerase chain reaction in 43.2% (35/81) of these women. The prevalence of IgG and IgA antibodies to HPV-16 virus-like particles (VLP-16) in oral fluid and was investigated by enzyme-linked immunosorbent assay. Anti-VLP-16 IgA antibodies were detected in oral fluid from 54.3% (44/81) of women with cervical neoplasia, compared with 8% (3/36) in controls (P = 0.000002). Anti-VLP-16 IgG was detected in oral fluid from 43.2.9% (25/72) and 13.3% (4/30; P = 0.029), respectively. Women who were HPV-16 DNA positive at their cervical lesion, displayed an oral fluid anti-VLP-16 IgA prevalence of 60.7% (17/28) and HPV-16 DNA negative women an oral fluid anti-VLP-16 IgA prevalence of 50% (20/40; P = 0.38). Oral fluid anti-VLP-16 IgG prevalence in HPV-16 DNA positive women was 28.6% (8/28) compared with 40% (16/40) in oral fluid from HPV-16 DNA negative women (P = 0.3). Amongst HPV-16 DNA positive women, the anti-VLP-16 IgG seroprevalence was 75% (21/28) and IgA seroprevalence 35.7% (10/28) and for the HPV-16 DNA negative women these values were 60% (24/40) and 32.5% (13/40), respectively. Oral IgA antibody testing proved no more sensitive than serum antibody detection for the determination of HPV infection but could be useful as a non-invasive screening method for women with cervical neoplasia and for estimating the mucosal antibody response to HPV vaccines.

Adolescent↗

The impact of human immunodeficiency virus type 1 status on human papillomavirus (HPV) prevalence and HPV antibodies in serum and cervical secretions.

Human immunodeficiency virus (HIV) type 1-infected (HIV-positive) and -uninfected (HIV-negative) sex workers were examined for the presence of cervical human papillomavirus (HPV) DNA. Cervicovaginal rinse and serum samples from these women were examined for IgG and IgA antibodies to HPV-16 virus-like particles (VLP-16) by ELISA. The HIV-positive women displayed a significantly higher prevalence of HPV DNA (40/47 [85%]) than did the HIV-negative women (22/52 [42%]; P=.00001). Both HIV-positive and HIV-negative sex workers displayed a high seroprevalence rate for anti-VLP-16 IgG antibodies (27/40 [68%] and 30/43 [70%], respectively), but significantly fewer HIV-positive women than HIV-negative women had anti-VLP-16 serum IgA (6/40 [15%] vs. 17/43 [40%], respectively; P=.012). Significantly more HIV-positive women than HIV-negative women had cervical anti-VLP-16 IgG antibodies (16/49 [33%] vs. 6/63 [10%], respectively; P=.002) but not IgA antibodies (P=.3).

Adolescent↗

Seroresponses to human papillomavirus types 16, 18, 31, 33, and 45 virus-like particles in South African women with cervical cancer and cervical intraepithelial neoplasia.

The aim of the study was to determine the prevalence of antibodies to human papillomavirus (HPV) types 16, 18, 31, 33, and 45 in woman in Cape Town with cervical intraepithelial neoplasia (CIN) (n = 95), cervical cancer (n = 40), female blood donors (n = 95) and children (n = 110). The enzyme-linked immunosorbent assay (ELISA) made use of baculovirus synthesised HPV virus like particles (VLPs) as antigen. Antibodies to at least one HPV type were detected in sera from 75% of cancer patients, 71.6% of CIN patients, 44.2% of blood donors and 27.3% of children. Sera from 95 women with CIN were compared with age-matched female blood donors. There was a significant association of seropositivity to VLP-16 (P = 0.006) and VLP-45 (P = 0.008) with CIN compared with the blood donors. There was also a significant difference in the seropositivity of women with CIN to any of the five virus-like particle (VLP) types compared to the blood donors (P = 0.0002: OR = 3.2). Thirty-nine of sixty-nine (56.5%) women with CIN were found to be HPV-16 DNA positive. The average age of women in this group that were VLP-16 seropositive was 34 years and those found to be VLP-16 seronegative was 52 years of age. Antibodies to all five VLP types were detected in these populations, thus an ideal vaccine should induce protection from infection by a wide range of HPV types.

Adult↗

Surgical treatment of adult primary hepatic sarcoma.

BACKGROUND: Primary sarcomas of the liver are extremely rare in adults. Optimal therapeutic approaches remain unclear. METHODS: Twenty consecutive adult patients who had surgical treatment for primary hepatic sarcomas were reviewed. Patient age ranged from 23 to 80 years. Other than one patient with primary hepatic angiosarcoma who had a history of thorium dioxide colloid (Thorotrast) exposure 23 years before diagnosis, no predisposing causes were apparent. Nineteen patients had hepatic resection and one patient had an orthotopic liver transplant. No patient received neoadjuvant chemotherapy or radiotherapy but radiotherapy was delivered intraoperatively in one patient. RESULTS: Leiomyosarcoma was the most common histological type of sarcoma diagnosed (five of 20 patients), followed by malignant solitary fibrous tumour (four) and epithelioid haemangioendothelioma (three). Fourteen tumours were high-grade sarcomas and six were low grade malignancies. Thirteen patients developed a recurrence. Distant metastases (ten patients) and intrahepatic recurrence (six) were the predominant sites of initial treatment failure. Six patients received salvage chemotherapy. Histological grade was the only factor significantly associated with overall patient survival (P= 0.03). With complete resection, patients with high-grade tumours had a 5-year survival rate of 18 (95 per cent confidence interval 5-62) per cent compared with 80 (52-100) per cent for patients with low-grade tumours. The 5-year survival rate for all 20 patients was 37 (20-60) per cent. CONCLUSION: Surgical resection is the only effective therapy for primary hepatic sarcomas at present. Better adjuvant therapy is necessary, especially for high-grade malignancies, owing to the high failure rate with operation alone.

Adult↗

Relation between duration and intensity of first exercise and "warm up" in ischaemic heart disease.

OBJECTIVE: To determine the importance of the duration and intensity of "warm up" exercise for reducing ischaemia during second exercise in patients with exertional angina. DESIGN: Randomised crossover comparison of three warm up exercise protocols. PATIENTS: 18 subjects with stable ischaemic heart disease and > 0.1 mV ST segment depression on treadmill exercise testing. INTERVENTIONS: The warm up protocols were 20 minutes of slow exercise at 2.7 km/h, symptom limited graded exercise for a mean of 7.4 (range 5.0 to 10.5) minutes, and three minutes of symptom limited fast exercise of similar maximum intensity. MAIN OUTCOME MEASURES: ST segment depression during graded treadmill exercise undertaken 10 minutes after each warm up protocol or no warm up exercise. RESULTS: Compared with exercise with no warm up, the duration of graded exercise after earlier slow warm up increased by 4.9% (95% confidence interval (CI), -3.3% to 13.7%), after graded warm up by 10.3% (95% CI, 5.6% to 15.2%), and after fast warm up by 16% (95% CI, 6.2% to 26.7%). ST segment depression at equivalent submaximal exercise decreased after slow warm up by 27% (95% CI, 5% to 44%), after graded warm up by 31% (95% CI, 17% to 44%), and after fast warm up by 47% (95% CI, 27% to 61%). Compared with slow warm up exercise, the more intense graded and fast warm up protocols significantly increased the duration of second exercise (p = 0.0072) and reduced both peak ST depression (p = 0.0026) and the rate of increase of ST depression (p = 0.0069). CONCLUSIONS: In patients with exertional angina the size of the warm up response is related to the maximum intensity rather than the duration of first exercise.

Aged↗

Reference chart derived from post-stent-implantation intravascular ultrasound predictors of 6-month expected restenosis on quantitative coronary angiography.

BACKGROUND: Intravascular ultrasound (IVUS)-guided stent implantation and the availability of a reference chart to predict the expected in-stent restenosis rate based on operator-dependent IVUS parameters may interactively facilitate optimal stent placement. The use of IVUS guidance protects against undue risks of dissection or rupture. METHODS AND RESULTS: IVUS-determined post-stent-implantation predictors of 6-month in-stent restenosis on quantitative coronary angiography (QCA) were identified by logistic regression analysis. These predictors were used to construct a reference chart that predicts the expected 6-month QCA restenosis rate. IVUS and QCA data were obtained from 3 registries (MUSIC [Multicenter Ultrasound Stenting in Coronaries study], WEST-II [West European Stent Trial II], and ESSEX [European Scimed Stent EXperience]) and 2 randomized in-stent restenosis trials (ERASER [Evaluation of ReoPro And Stenting to Eliminate Restenosis] and TRAPIST [TRApidil vs placebo to Prevent In-STent intimal hyperplasia]). In-stent restenosis was defined as luminal diameter stenosis >50% by QCA. IVUS predictors were minimum and mean in-stent area, stent length, and in-stent diameter. Multiple models were constructed with multivariate logistic regression analysis. The model containing minimum in-stent area and stent length best fit the Hosmer-Lemeshow goodness-of-fit test. This model was used to construct a reference chart to calculate the expected 6-month restenosis rate. CONCLUSIONS: The expected 6-month in-stent restenosis rate after stent implantation for short lesions in relatively large vessels can be predicted by use of in-stent minimal area (which is inversely related to restenosis) and stent length (which is directly related to restenosis), both of which can be read from a simple reference chart.

Clinical Trials as Topic↗

Hypermethylation of the MYF-3 gene in colorectal cancers: associations with pathological features and with microsatellite instability.

Myf-3 is the human homologue of the murine Myo-D1 gene involved in muscle-cell differentiation. Using Southern blot analysis, we examined methylation of Myf-3 in histologically normal colonic mucosae, adenomas and carcinomas from a large series of patients with primary colorectal cancer. Hypermethylation of this gene in comparison with normal mucosa was observed in 88% of adenomas and in 99% of carcinomas. The pattern of Myf-3 methylation was similar in different areas of the same tumour, suggesting that methylation imbalances occur before the bulk of clonal-cell expansion. Significantly increased levels of Myf-3 methylation were observed in tumours which were more invasive, located in the proximal colon or from older patients. Patients whose tumours had extensive methylation showed a trend for shortened survival, though this was probably related to their being more invasive. Extensive methylation was significantly more frequent in tumours with microsatellite instability. Further work is required to determine whether the hypermethylation of Myf-3 observed in colorectal cancers is a specific alteration with functional significance or whether it reflects non-specific methylation imbalances occurring early during tumorigenesis.

Adenoma↗

Factors affecting socket fixation after cemented revision.

Factors influencing the radiographic outcome of revised cemented sockets have been investigated in 360 cases; 70 with radiological signs of failure were analysed. The acetabular bone stock at revision and preparation of the acetabular floor were the two factors which had a significant influence on the outcome. The thickness of the cement mantle around the socket also had an influence. Young patients were at a higher risk of failure. The use of a flanged socket and an acetabular cement pressuriser appeared to improve the radiographic result, but this was not statistically significant.

Acetabulum↗