Short term blood pressure and metabolic effects of tibolone in postmenopausal women with non-insulin dependent diabetes.
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Aged↗
Biomedical subjects
A Cox
Publications and source records attributed to A Cox.
Report and abstracts of the Fourth International Workshop on Human Chromosome 2 Mapping 1996.
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Chromosome Mapping↗
Dry bones: a paleopathological study of skeletal remains from a medieval graveyard in Dundee.
We report a study on human skeletal remains excavated from a medieval city centre graveyard. The remains of approximately 75 individuals were examined and radiographs were made of selected specimens. Many bones were normal and apparently from strong, young adults. The most frequent abnormality was osteoarthritis but we also noted osteoporosis, periostitis and an example of probable Paget's disease. From measurements of long bones and using appropriate formulae, we estimated stature. The average height for males was calculated to be 172cm (5' 7") and for females 157 cm (5' 2").
Anthropology, Physical↗
Psychological markers in the detection of autism in infancy in a large population.
BACKGROUND: Investigation to see if there are key psychological risk indicators for autism in a random population study of children at 18 months of age; and to assess how well these discriminate children who receive a diagnosis of autism from other forms of developmental delay. METHOD: Sixteen thousand children in the southeast of England were screened for autism by their health visitor or GP, during their routine 18-month-old developmental check-up, using the CHAT (Checklist for Autism in Toddlers). From a previous high-risk study we predicted that children at 18 months of age who failed three items ('protodeclarative pointing', 'gaze-monitoring', and 'pretend play') would be at risk for receiving a diagnosis of autism. From other evidence, we further predicted that those 18-month-olds who failed one or two of the key items (either pretend play, or protodeclarative pointing and pretend play) would be at risk for developmental delay without autism. RESULTS: Twelve children out of the total population of 16,000 consistently failed the three key items. Of these, 10 (83.3%) received a diagnosis of autism. Thus, the false positive rate was 16.6% (2 out of 12 cases), and even these 2 cases were not normal. When the 10 children with autism were reassessed at 3.5 years of age, their diagnosis remained the same. Thus the false positive rate among the cases diagnosed with autism was zero. In contrast, of 22 children who consistently failed either protodeclarative pointing and/or pretend play, none received a diagnosis of autism, but 15 (68.2%) received a diagnosis of language delay. CONCLUSIONS: Consistent failure of the three key items from the CHAT at 18 months of age carries an 83.3% risk of autism; and this pattern of risk indicator is specific to autism when compared to other forms of developmental delay.
Autistic Disorder↗
Cytokines as genetic modifying factors in immune and inflammatory diseases.
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Autoimmune Diseases↗
Angiotensin-converting enzyme (ACE) gene polymorphism and the erythrocyte sodium-lithium countertransporter (SLC) phenotype in hypertension.
It has been suggested that the association between altered behaviour of the erythrocyte sodium-lithium countertransporter (SLC) and hypertension could be secondary to its association with the risk of vascular disease rather than raised blood pressure (BP) per se. Homozygosity for the angiotensin-converting enzyme (ACE) deletion allele has also been linked to a more severe phenotype for cardiovascular disease. The present study investigated whether there is an association between these two indicators of vascular risk in patients with hypertension. The kinetic characteristics of the countertransporter (SLC activity, Vmax and KNa) of patients having the ID ACE-genotype (n = 16) were compared with those patients who had the DD genotype (n = 12). The median (range) SLC activity (mmol Li/l Red Blood Cells.h) in the ID (0.221 [0.061-0.422]) and DD (0.173 [0.094-0.408]) groups were similar (P = 0.28; Mann-Whitney). No significant differences in Vmax (mmol Li/l RBC.h) emerged between the two study groups (0.279 + 0.124 [ID] vs 0.244 + 0.123 [DD]; P = 0.46; unpaired Student's t-test); similarly, no differences emerged between the two groups with respect to KNa (median [range]; ID, 39.8 [12.4-84.4] vs DD, 35.9 [14.6-78.3]; P = 0.47). These data suggest that the SLC phenotype and the ACE-D allele dose are risk factors for cardiovascular disease that function independently of one another.
Aged↗
Functional expression and recognition of nonclassical MHC class I T10b is not peptide-dependent.
Studies of classical and nonclassical MHC class I molecules have shown that unique peptides are associated and functionally recognized by alloreactive T cells. We have recently shown that an alloreactive TCR-gamma delta cell recognizes a nonclassical MHC molecule, T10b. However, T cell recognition of this glycoprotein did not appear to require typical peptide recognition based on studies using transporter-defective mutant cell lines. In the current study, we have analyzed in detail, the role of peptide in T10b expression and recognition. The findings reveal that the recognition of the nonclassical MHC molecule by TCR-gamma delta cells is independent of species, tissue type, both the class I and class II Ag processing and presentation pathways, or the presence of peptides. In fact, biochemical analysis of the T10b chimeric molecule, T10b/Ld, transfected into CHO cells using radiolabeled [3H]leucine, HPLC, and mass spectrometry suggest that peptides are not associated with this nonclassical class I molecule. Therefore, some class I molecules, e.g., T10b, do not associate with polymorphic peptides typical of classical MHC class I molecules and can be expressed in the absence of peptides on the cell surface in a functionally active form.
Animals↗
A comparison of individual and family approaches to initial assessment.
The study aimed to examine the influence of initial mode of assessment on attendance, and later assessment and treatment. 100 children newly referred to a child mental health service were randomly assigned to (i) initial family assessment; child and family seen together, or (ii) individual assessment, child and parents seen in parallel. Those invited were more likely to attend following "individual" appointment letters because parents did not always bring all the children in response to "family" appointment letters. Failure to attend the second appointment occurred twice as often if there was a change in who was asked to attend. Psychometric assessment was more often requested following an initial family interview. Long term mode of therapy appeared to be partly but not wholly influenced by initial assessment method. Results suggest that sustained co-operation with long term therapy is more likely to occur when clinicians vary the family members they are working with according to the needs of the case.
Child↗
The Child and Adolescent Psychiatric Assessment (CAPA).
Great advances have been made during the last 20 years in the development of structured and semi-structured interviews for use with psychiatric patients. However, in the field of child and adolescent psychiatry there have been weaknesses in the specification and definition of both symptoms and the psychosocial impairments resulting from psychiatric disorder. Furthermore, most of the available interviews for use with children have been tied to a single diagnostic system (DSM-III, DSM-III-R, or ICD-9). This has meant that symptom coverage has been limited and nosological comparisons have been inhibited. The Child and Adolescent Psychiatric Assessment (CAPA) represents an attempt to remedy some of these shortcomings. This paper outlines the principles adopted in the CAPA to improve the standardization, reliability and meaningfulness of symptom and diagnostic ratings. The CAPA is an interviewer-based diagnostic interview with versions for use with children and their parents, focused on symptoms occurring during the preceding 3 month period, adapted for assessments in both clinical and epidemiological research.
Adolescent↗
SPARC gene expression is reduced in early diabetes-related kidney growth.
Renal enlargement is a characteristic feature of diabetes in humans and experimental animals that may predict subsequent renal disease. The biological processes involved in diabetes-related kidney growth are complex and involve changes in extracellular matrix, cell hypertrophy and hyperplasia. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix protein with anti-adhesive, antiproliferative and matrix remodeling properties. We examined kidney SPARC gene expression and protein content in early experimental diabetes. By Northern blot analysis, kidney SPARC mRNA fell in diabetic animals at day 1 to 40 +/- 15% of controls levels (mean +/- SEM, P < 0.01) to 42% +/- 11% on day 3 (P < 0.01) with a further decrease at day 7 to 29 +/- 7% (P < 0.001). In situ hybridization demonstrated SPARC mRNA within glomeruli renal interstitial cells and in blood vessels but not in tubular epithelial cells. SPARC mRNA was decreased in diabetic rats within a change in the pattern of distribution. By immunofluorescence, SPARC protein was detected in glomeruli and tubular basement membrane. Diabetes was associated with a decrease in SPARC protein at both sites. These data demonstrate that the onset of diabetes-related kidney growth is associated with a reduction in SPARC mRNA and protein. In the context of the known biological actions of SPARC, the findings in the present study implicate this matrix protein in the pathogenesis of diabetes related kidney growth.
Animals↗
Association of angiotensin converting enzyme DD genotype with hypertension in diabetes.
Angiotensin converting enzyme (ACE) genotypes have been associated with hypertension in the general population. However, the relation of ACE genotype to the prevalence of hypertension in diabetic populations is less clear. This study investigated ACE genotypes in 100 patients with diabetes mellitus, of whom 41 were on anti-hypertensive medication. A significant association was found between the presence of the ACE-D allele and hypertension in both the overall diabetic group (D = 0.66, P < 0.01) and in the subset of diabetics who had non-insulin-dependent diabetes (D = 0.69, P < 0.001). There was no correlation of ACE genotype with hypertension in insulin-dependent diabetes (D = 0.57).
Adolescent↗
A rapid test for endotoxin in whole blood.
A rapid whole blood agglutination test has been developed for the detection of endotoxin. The test reagent consists of polymyxin B (PmB) conjugated to the Fab fragment of the anti-glycophorin antibody 1C3/86. After addition of reagent to whole blood, red cell agglutination occurs within two minutes in samples from endotoxaemic patients or with the addition of either whole Gram negative bacteria, supernatants from Gram negative bacterial cultures or purified endotoxin. In clinical samples there was a strong correlation (r = 0.83) between the strength of agglutination and the level of endotoxin measured by the Limulus amaebolysate test (LAL). The prospect of a rapid and accurate test for endotoxin may enable better clinical management of Gram negative sepsis.
Adult↗
Comparative analysis of the genetic associations of HLA-DR3 and tumour necrosis factor alpha with human IDDM.
Insulin-dependent diabetes mellitus (IDDM) is associated with class II molecules of the MHC on chromosome 6, in particular HLA-DR and -DQ alleles, but a pathogenic role for TNF-alpha in the class III region of the MHC has also been implied. We therefore tested whether there was any independent association between a biallelic TNF polymorphism and IDDM. The TNF2 allele was present in 61 of 114 (54%) IDDM patients compared to 101 of 253 (40%) control subjects (odds ratio 1.73; p < 0.02). Stratification analysis in individuals matched for HLA-DR3 revealed, however, that this association was not independent of HLA-DR3 and is most likely to be a result of linkage disequilibrium between these alleles.
Adult↗
Head and neck tumors after energetic proton irradiation in rats.
This is a two-year progress report on a life span dose-response study of brain tumor risk at moderate to high doses of energetic protons. It was initiated because a joint NASA/USAF life span study of rhesus monkeys that were irradiated with 55-MeV protons (average surface dose, 3.5 Gy) indicated that the incidence of brain tumors per unit surface absorbed dose was over 19 times that of the human tinea capitis patients whose heads were exposed to 100 kv x-rays. Examination of those rats that died in the two-year interval after irradiation of the head revealed a linear dose-response for total head and neck tumor incidence in the dose range of 0-8.5 Gy. The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. The estimated dose required to double the number of all types of head and neck tumors was 5.2 Gy. The highest dose, 18 Gy, resulted in high mortality due to obstructive squamous metaplasia at less than 50 weeks, prompting a new study of the relative biological effectiveness of high energy protons in producing this lesion.
Adenoma↗
Teratozoospermia and in-vitro fertilization: a randomized prospective study.
A prospective randomized study was conducted to assess the prognostic value of sperm morphology in an in-vitro fertilization (IVF) programme, using strict criteria. The first group (T, teratozoospermic) included 32 couples with an isolated teratozoospermia in the male partner (morphology < 9% normal). The second group (C, control) contained 36 couples with normal semen parameters, including morphology (> 9% normal, strict criteria). In both groups, 50 IVF cycles were performed. Patients were matched for indication for IVF. There was no difference between the two groups regarding age, duration of infertility, stimulation protocol, catheter used for embryo transfer and different sperm parameters. A statistically significant difference between the T and C groups respectively was observed regarding the fertilization rate (69.2 and 79.4%, P < 0.05), pregnancy rate per cycle (12.0 and 42%, P < 0.001), the pregnancy rate per transfer (13.9 and 42.0%, P < 0.01) and per embryo transferred (6.1 and 14.8%, P < 0.05). No pregnancy occurred in the poor prognosis group (morphology < 5% normal). In cases of moderate teratozoospermia, the fertilization rate appeared normal (78.6%) but the conception rate remained low. We concluded that the use of strict criteria in the assessment of sperm morphology is useful in predicting fertilization and pregnancy rate in the human in-vitro model.
Embryo Transfer↗
Neutralizing monoclonal antibodies to an extracellular Pseudomonas cepacia protease.
Pseudomonas cepacia produces at least two extracellular proteases with apparent molecular masses of 36,000 and 40,000 Da. The 36-kDa protease has high proteolytic activity and the 40-kDa protease has low proteolytic activity with hide powder azure as a substrate. Monoclonal antibodies (MAbs) were raised against the purified 36- and 40-kDa proteases. Several MAbs directed against the 36-kDa protease were found to recognize the 40-kDa protease by Western immunoblot analysis. Similarly, a MAb directed against the 40-kDa protease recognized the 36-kDa protease, suggesting that these two proteases may be immunologically related. A MAb directed against the 36-kDa protease, designated 36-6-8, and a MAb directed against the 40-kDa protease (MAb G-11) cross-reacted with other extracellular proteases, such as Pseudomonas aeruginosa elastase and alkaline protease, Pseudomonas pseudomallei protease, and the Vibrio cholerae hemagglutinin/protease. MAb 36-6-8 neutralized the P. cepacia 36-kDa protease, P. aeruginosa elastase, P. pseudomallei protease, and V. cholerae hemagglutinin/protease but did not affect P. aeruginosa alkaline protease activity. In contrast, MAb G-11 to the 40-kDa protease neutralized only the P. cepacia 36-kDa protease. This evidence suggests that the neutralizing MAb, 36-6-8, recognizes an epitope conserved among some metalloproteases. This epitope may lie at or near the active site of the P. cepacia 36-kDa protease and P. aeruginosa elastase.
Antibodies, Bacterial↗
Effect of beta blockade on the neurohumoral and cardiopulmonary response to dynamic exercise in cardiac transplant recipients.
OBJECTIVE: To determine the effects of a small dose of beta blocker on neurohumoral and cardiopulmonary responses after cardiac transplantation. BACKGROUND: Cardiac transplant recipients have a reduced exercise capacity and abnormal cardiovascular responses to exercise. The sympathoadrenal response to exercise has been shown to be abnormal with high venous noradrenaline. The effect of beta blockade on these neurohumoral mechanisms has not been defined. METHODS: 10 non-rejecting cardiac transplant recipients were studied. Patients carried out graded exercise to a symptom limited maximum. Blood samples were taken during exercise. Concentrations of noradrenaline, adrenaline, and atrial natriuretic peptide and plasma renin activity were measured. The next day, the exercise and sampling procedure were repeated after an oral dose of propranolol (40 mg). RESULTS: Patients tolerated exercise poorly after beta blockade, which was reflected in the maximum workload reached. Heart rate and blood pressure were significantly higher at rest and during exercise before beta blockade. Although there was no significant difference when resting, mean (SEM) noradrenaline concentrations during peak exercise were higher after beta blockade (16.2 (2) v 23.6 (2.9) nmol/l, p = 0.001). Adrenaline concentrations at peak exercise were also greater after beta blockade (0.89 (0.31) v 1.18 (0.38) nmol/l, p = 0.055). Atrial natriuretic peptide concentrations tended to be higher after beta blockade (118.75 (50.2) v 169.79 (39.3) pmol/l, p = 0.36). There was no significant change in plasma renin activity. CONCLUSIONS: A small oral dose of a competitive beta blocker such as propranolol has an adverse effect on exercise tolerance and cardiovascular response to exercise in cardiac transplant recipients. There are also increased concentrations of circulating noradrenaline and therefore, sympathetic activity during exercise. beta blockers should be used with caution in cardiac transplant recipients.
Administration, Oral↗
A defect of platelet aggregation associated with an abnormal distribution of glycoprotein IIb-IIIa complexes within the platelet: the cause of a lifelong bleeding disorder.
A young Italian man (A.P.) has a lifelong history of bleeding from gums and mucocutaneous tissue. Electron microscopy showed a wide diversity of platelet size including giant forms. In citrated platelet-rich plasma (PRP), platelet aggregation induced by adenosine diphosphate (ADP) and other agonists was much reduced. Both secretion and clot retraction were normal. The aggregation of washed platelets with ADP was improved but remained subnormal, as was aggregation with collagen and thrombin. Fibrinogen-binding was analyzed by flow cytometry using platelets in whole blood or PRP and was markedly decreased. Crossed immunoelectrophoresis of Triton X-100 extracts of (A.P.) platelets showed that GP IIb-IIIa levels were 40% to 50% of normal. Glycoprotein (GP) IIb and GP IIIa were of usual migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but their labeling was much reduced during lactoperoxidase-catalyzed iodination. Binding to (A.P.) platelets of four different 125I-labeled monoclonal antibodies to GP IIb-IIIa complexes was reduced to 12% to 20% of normal levels. However, when the patient's platelets were stimulated with alpha-thrombin, monoclonal antibody binding showed the same increase (approximately 20,000 sites) as normal platelets. Both flow cytometry and immunocytochemical studies showed that the distribution of residual surface GP IIb-IIIa within the total (A.P.) platelet population was heterogeneous and not related to platelet size. Staining of ultrathin sections confirmed the presence of an internal pool of GP IIb-IIIa. Monoclonal antibodies to other membrane glycoproteins bound normally to (A.P.) platelets. The patient has a selective deficiency of the surface pool of GP IIb-IIIa complexes that is manifested clinically by a mild Glanzmann's thrombasthenia-like syndrome.
Adenosine Diphosphate↗