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Biomedical subjects

K Owen

Publications and source records attributed to K Owen.

At least 19 recordsLinked to original sources
PubMed2002

[Changes in levels of acute phase proteins in patients with central hypercortisolism].

BACKGROUND: Acute phase protein reaction depends on complex interaction of proinflammatory cytokines and hormones, especially glucocorticoids. Glucocorticoids are essential factors for hepatocellular microenvironment and proteosynthesis during both rest and inflammatory period. Cushing's disease represents a model of glucocorticoid hyperstimulation of acute phase protein synthesis without interleukin-6 and other cytokine influence. METHODS AND RESULTS: 20 patients (age of 38 +/- 11, 11 males, 9 females) with a diagnosis of central hypercorticolism were examined. Plasma levels of 11 acute phase proteins were estimated. These results were compared with plasma ACTH, interleukin-6, and U-cortisol concentrations and correlated to the control group (healthy volunteers, age 30 +/- 5, 13 males, 7 females). Plasma levels of albumin and prealbumin in patients with Cusing's disease were significantly lower. We proved significant elevation of alpha 1-acid glycoprotein, haemopexin, and fibrinogen compared with healthy subjects. The positive correlation of alpha 1-acid glycoprotein and U-cortisol (r = 0.51, p < 0.01), haemopexin and U-cortisol (r = 0.47, p < 0.05) respectively was found. CONCLUSIONS: The interaction between glucocorticoids and proinflammatory cytokines in acute phase protein synthesis depends on permissive effects of corticoids on cytokine signal transduction in hepatocytes. However, our results document that corticoida themselves significantly stimulate acute phase protein synthesis, and this stimulation differs from inflammatory pattern of hepatic proteosynthesis.

Acute-Phase Proteins↗
PubMed2002

[Obesity, type 2 diabetes and their quantitative relation].

Diabetes type 2 and obesity are diseases which have marked mutual relations. The pathogenesis of these relations is in many respects obscure. Also the molecular biological knowledge of the two diseases is inadequate so far. In the submitted brief paper the authors present only a review of some quantitative aspects of the relationship of obesity and diabetes supplemented by some of their own results. The authors summarize the epidemiological relations of diabetes and obesity, possible prediction of the development of diabetes in obese subjects, possible prevention of diabetes in obese subjects and possible treatment of obese diabetics. Slight weight reduction, e.g. by using modern anti-obesity drugs is of fundamental importance for reducing the incidence of diabetes and for its treatment. Based on their own experience the authors present their own results of cluster and factor analysis for evaluating the links between diabetes and obesity with the metabolic syndrome. The authors' work similarly as work quoted in the discussion indicate that diabetes as well as obesity are beyond the so-called nucleus of the metabolic syndrome. Even slight body weight reduction by 5-10%, within the reach of everybody, influences in a fundamental way the incidence and compensation of diabetes as well as other components of the metabolic syndrome.

Cluster Analysis↗
PubMed2001

Maturity-onset diabetes of the young: from clinical description to molecular genetic characterization.

Maturity-onset diabetes of the young is a heterogeneous group of autosomal dominantly inherited, young-onset beta-cell disorders. At least two consecutive generations are affected with a family member diagnosed before 25 years of age. Diabetes is caused either by mutations in the glucokinase gene (glucokinase MODY) or by mutations in transcription factors (transcription factor MODY). Glucokinase maturity-onset diabetes of the young is a mild, non-progressive hyperglycaemia caused by a resetting of the pancreatic glucose sensor. It is treated with diet, and complications are rare. Pregnancies affected by glucokinase mutations have specific management strategies and prognosis. Transcription factor maturity-onset diabetes of the young, caused by mutations in the hepatocyte nuclear factor genes HNF-1alpha, HNF-4alpha and HNF-1beta, and in insulin promoter factor-1 results in a progressive beta-cell defect with increasing treatment requirements and diabetic complications. Cystic renal disease is a prominent feature of HNF-1beta mutations. Further maturity-onset diabetes of the young genes remain to be identified. MODY is part of the differential diagnosis of diabetes presenting in the first to third decades of life. Diagnostic molecular genetic testing is available for the more common genes involved.

Adult↗
PubMed2001

Multifocal fibrosclerosis: a case of thyroiditis and bilateral lacrimal gland involvement.

A patient with invasive fibrous thyroiditis (Riedel's thyroiditis), dysphagia, and bilateral lacrimal gland involvement is described. Resolution of the thyroid mass and orbital swellings followed corticosteroid therapy. The unusual ocular features of this case are briefly discussed and the use of corticosteroid and other immunosuppressant therapy in multifocal fibrosclerosis is reviewed.

Adrenal Cortex Hormones↗
PubMed2001

beta-cell genes and diabetes: molecular and clinical characterization of mutations in transcription factors.

beta-Cell transcription factor genes are important in the pathophysiology of the beta-cell, with mutations in hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, insulin promoter factor (IPF)-1, HNF-1beta, and NeuroD1/BETA2, all resulting in early-onset type 2 diabetes. We assessed the relative contribution of these genes to early-onset type 2 diabetes using linkage and sequencing analysis in a cohort of 101 families (95% U.K. Caucasian). The relative distribution of the 90 families fitting maturity-onset diabetes of the young (MODY) criteria was 63% HNF-1alpha, 2% HNF-4alpha, 0% IPF-1, 1% HNF-1beta, 0% NeuroD1/ BETA2, and 20% glucokinase. We report the molecular genetic and clinical characteristics of these patients including 29 new families and 8 novel HNF-1alpha gene mutations. Mutations in the transactivation domain are more likely to be protein truncating rather than result in amino acid substitutions, suggesting that a relatively severe disruption of this domain is necessary to result in diabetes. Mutations in the different transcription factors result in clinical heterogeneity. IPF-1 mutations are associated with a higher age at diagnosis (42.7 years) than HNF-1alpha (20.4 years), HNF-1beta (24.2 years), or HNF-4alpha (26.3 years) gene mutations. Subjects with HNF-1beta mutations, in contrast to the other transcription factors, frequently present with renal disease. A comparison of age at diagnosis between subjects with different types and locations of HNF-1alpha mutations did not reveal genotype-phenotype correlations. In conclusion, mutations in transcription factors expressed in the beta-cell are the major cause of MODY, and the phenotype clearly varies with the gene that is mutated. There is little evidence to indicate that different mutations within the same gene have different phenotypes.

Adolescent↗
PubMed2001

[Weight reduction and aspects of the metabolic syndrome].

We carried out analysis of the influence of long-term weight reduction on individual parameters of metabolic syndrome X. We enrolled the total of 30 obese patients (22 with, 8 without syndrome X). During weight reduction, the mean BMI decreased by 4.08 +/- 3.00 kg/m2 leading to significant (p < 0.001) decrease in insulinaemia from 33.4 +/- 25.9 to 21.2 +/- 19.625 mu j/ml. In patients with syndrome X, the decrease in BMI of 3.50 +/- 2.76 kg/m2 was coupled with significant (p < 0.001) decrease in insulinaemia from 39.7 +/- 27.7 to 24.0 +/- 21.725 mu j/ml. Using cluster analysis of cases syndrome X patients formed two distinctive groups with different behaviour. It seems, that diagnosis of metabolic syndrome, based on arbitrary criteria, encompasses stable patients, in our study characterized by higher age and presence of hypertension, and volatile patients, who form somewhat transition stage between simple obesity and fully developed syndrome X. Moreover, relationships between individual parameters at the beginning of the study can elucidate the environmental influences (relationship between insulinaemia and hypertension), whereas those at the end of the study represent true pathogenetic relationships (insulinaemia and glycaemia) and relationships between syndrome X constituents (hypertension, hypertriglyceridaemia and decrease in HDL cholesterol).

Adult↗
PubMed1999

A comparative study of the repeat dose toxicity of grepafloxacin and a number of other fluoroquinolones in rats.

Grepafloxacin is a new oral fluoroquinolone with potent activity against community acquired respiratory pathogens, including Streptococcuspneumoniae, and pharmacokinetic properties which allow once daily dosing. As part of its safety evaluation a study of 4 weeks duration was performed to compare the toxicity of grepafloxacin with that of a number of commercially available quinolones in the rat. Groups of eight male Sprague-Dawley rats received either control material or grepafloxacin, enoxacin, lomefloxacin, ofloxacin or ciprofloxacin at an oral dosage of 300 mg/kg/day for 4 consecutive weeks. Effects related to the antibacterial activity of the drugs were seen as increased caecal weight, decreased urinary excretion of sodium, increased water consumption, decreased urine volume, increased urine osmolality, soft stools and suppressed body weight gain. It is well documented that fluoroquinolones can cause lesions in the cartilage of the major diarthrodial joints, and blister formation or erosion on the joint surface was observed in all quinolone-treated groups other than the grepafloxacin group. Some quinolones, have been found to cause crystalluria, which is often associated with secondary nephropathy in laboratory animals due to the poor solubility of quinolones under the alkaline conditions of the urine. In the present study, needle-like crystals in the urinary sediment were observed in enoxacin and ciprofloxacin treated groups only. In conclusion, grepafloxacin was well tolerated and showed a low potential for joint toxicity and crystalluria compared to other quinolones.

Animals↗
PubMed1999

The comparative arthropathy of fluoroquinolones in dogs.

1. Fluoroquinolone antibiotics are generally only prescribed to paediatric patients on compassionate grounds. This is because they are known to cause lesions in the cartilage of the major diarthroidal joints in immature experimental animals. As dogs are considered to be the most sensitive species, a series of studies was performed to compare the potential for grepafloxacin (a new fluoroquinolone) to cause arthropathy to that of ofloxacin and ciprofloxacin in juvenile (3 month old) beagles. 2. Grepafloxacin was administered once daily to male juvenile dogs at dosages of up to 100 mg/kg/day (intravenously), 60 mg/kg/day (orally) or 30 mg/kg/day (subcutaneously) for 1 week. Blister formation was observed on the surface of the joints in one of the three animals treated with grepafloxacin intravenously at 100 mg/kg/day. No abnormalities were observed at lower dosages or when grepafloxacin was administered orally or subcutaneously, regardless of dose. In animals treated with ofloxacin or ciprofloxacin at dosages of 10-30 mg/kg/day, blister formation or erosion was observed on the surface of joints regardless of dose or route of administration. 3. Histopathological examination of the joint surfaces of affected animals revealed the loss of cartilaginous matrix and chondrocytes, cavitation within the intermediate zone of cartilage accompanied by cartilage fibrillation or chondrocyte clustering, or loss of the surface layer which covers the cavitation (or loss of outer wall of the cavity). These findings were not present in the absence of grossly observed lesions. 4. Absorption following oral administration of grepafloxacin was low. Examination of plasma concentrations of drug following intravenous administration showed that joint toxicity was seen with ofloxacin and ciprofloxacin at maximum concentrations as low as 3.80 and 4.24 mg/l, respectively, while plasma levels of grepafloxacin of up to 11.95 mg/l failed to cause such lesions. When the concentration of grepafloxacin was 18.69 mg/l a single joint lesion was seen. Following subcutaneous administration of grepafloxacin, systemic exposure (area under the curve) of approximately 1.5 times that seen in man was not associated with joint lesions. However, lesions were noted for ofloxacin and ciprofloxacin treated animals at exposures equal to or below those seen in man. Therefore grepafloxacin appeared to have a relatively low potential for joint toxicity; this was not due to lack of penetration into the synovial fluid.

Animals↗
PubMed1998

Comparative grepafloxacin phototoxicity in mouse skin.

This study was performed in order to compare the phototoxic potential of grepafloxacin (a new fluoroquinolone for the treatment of respiratory tract infections) with that of a number of marketed fluoroquinolones. Groups of Balb/c mice received either control material or grepafloxacin, lomefloxacin, sparfloxacin, ofloxacin, ciprofloxacin or enoxacin at an oral dose of 200 mg/kg before being exposed to 20 J/cm2 longwave ultraviolet irradiation for 110-115 min. Lomefloxacin and sparfloxacin caused erythema and oedema which were often severe and lasted the full 7 days of the study. Enoxacin caused a long-lasting erythema, while the erythema seen following the administration of grepafloxacin, ciprofloxacin and ofloxacin was relatively mild and short-lived. The results of this study demonstrate the good safety profile of grepafloxacin in terms of phototoxicity.

Alopecia↗
PubMed1995

Unemployment and mental health.

The literature review has been carried out to examine current evidence linking mental health and unemployment. The research reviewed in this paper covers a wide range of academic disciplines spanning epidemiological medical research to more descriptive papers from social policy and geography, and while international material is included, the work concentrates on British literature. The paper examines published accounts of the relationship between mental health, suicidal behaviour and employment giving special attention to the influence of the variables, age and gender, on the experience of unemployment. All the literature reviewed suggests a link between unemployment and mental health problems. However, the direction of this link, that is whether unemployment is the cause of poor mental health or the result of poor mental health, is not clear. This paper will be of interest to a wide range of community health professionals, especially those working in areas affected by unemployment or mental health professionals working with individuals who recently have been made redundant.

Female↗
PubMed1995

The preclinical toxicological evaluation of sumatriptan.

1 Sumatriptan is a potent and selective 5-HT1 receptor agonist marketed for the treatment of migraine by both oral and subcutaneous routes. An extensive toxicological programme employing high doses of sumatriptan was carried out in a range of animal species. The studies evaluated both the local and systemic tolerance to single and repeated dosing, effects on all stages of reproduction, as well as the genotoxic and oncogenic potential of sumatriptan. 2 The administration of relatively high single and repeated doses of sumatriptan was well tolerated by both rodents and dogs by the oral, subcutaneous and intravenous routes. Behavioural effects, suggestive of involvement of the central nervous system, were the most obvious result of such doses and were generally more pronounced in dogs than rodents. The reason for this may be related to the higher plasma concentrations of the drug achievable in dogs. Additional observations restricted to dogs, were transient, and included tachycardia, facial oedema and breaks in the continuity of secretion films on the corneal surface. A tendency for an increase in weight gain was seen for rats, while a slight decrease was usually seen for dogs. The only pathological changes related to treatment with high concentrations of sumatriptan consisted of local reactions at the site of subcutaneous administration. 3 Sumatriptan is an indole; the structures of this chemical class show varying propensities for nitrosation. However, appropriate testing with sumatriptan failed to identify any mutagenic nitroso compounds. 4 Sumatriptan was neither genotoxic nor oncogenic. 5 Reproductive studies demonstrated that sumatriptan was not teratogenic and had no effect on peri- and postnatal development. Some embryotoxicity was observed, but only at maternally toxic doses. A slight decrease in the success of insemination was also noted at high oral doses in rats. 6 Results of the toxicological programme performed in support of migraine therapy with sumatriptan provide good assurance of safety for subcutaneous and oral use.

Administration, Oral↗
PubMed1994

Spearman's hypothesis and test score differences between whites, Indians, and blacks in South Africa.

Numerous studies in the United States have shown that mean test scores between Blacks and Whites differ by about one standard deviation. It has further been noted that the magnitudes of these differences vary on different tests. This variation can be explained by Spearman's hypothesis, which states that Black-White differences on a set of cognitive tests are positively associated with the tests' g loadings (the general intellectual ability). The present study, conducted among Black, Indian, and White secondary students in South Africa, showed mean Black-White differences of two standard deviations, indicating that the American results of one standard deviation are not universally correct. With regard to Spearman's hypothesis, it was found that, although the mean White-Indian differences were about one standard deviation, these differences did not support the hypothesis. Results pertaining to the Black-White differences were ambiguous; the correlation of .62 (p < .05) between the Black g and the Black-White differences strongly supported the hypothesis. A nonsignificant correlation of .23 was obtained between the White g and the Black-White differences. Possible reasons for this finding are discussed.

Adolescent↗
PubMed1994

Toxicity of a novel HMG-CoA reductase inhibitor in the common marmoset (Callithrix jacchus).

1. GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1 day-1 were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7.5 and 20 mg kg-1 day-1 for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days. 2. Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes. There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1 day-1 and above. 3. Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment. 4. Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity. 5. Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function. 6. HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.

Administration, Oral↗
PubMed1993

Sex differences in primary cognitive abilities among blacks, Indians and whites in South Africa.

Sex differences are reported for samples of approximately 1000 16-year-old blacks, Indians and whites in South Africa on ten tests of cognitive ability. Males obtained significantly higher means on non-verbal reasoning, spatial and mechanical aptitude, and females obtained significantly higher means on perceptual speed and memory for meaning (except among the black sample). In general the sex differences in South Africa are consistent with those typically obtained in the United States.

Adolescent↗