Biomedical subjects

B Shine

Publications and source records attributed to B Shine.

At least 19 recordsLinked to original sources

PubMed2005

Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up.

BACKGROUND: Craniopharyngiomas account for 2-5% of all primary intracranial tumours. Despite their benign histological appearance, they are often associated with an unfavourable prognosis and their optimal treatment remains controversial. AIM: To analyse the natural history and treatment outcome of children and adults presenting to the Departments of Paediatrics and Endocrinology with craniopharyngioma between 1964 and 2003. PATIENTS AND METHODS: The records of 121 patients (age range 2.5-83 years, 42 aged < 16 and 79 aged > or = 16) were identified. The mean follow-up period since presentation was 103 months (8.6 years) (range 0.3-468 months). Sixteen patients underwent gross total removal (A), 3 gross total removal + radiotherapy (B), 51 partial removal (C), 33 partial removal + radiotherapy (D), 6 cyst evacuation alone (E) and 3 cyst evacuation + radiotherapy (F). The clinical, imaging and endocrinological data at presentation and during follow-up were analysed. RESULTS: Headache and visual field defects were the most common presenting clinical features (64% and 55%, respectively). Ninety-four per cent of the tumours had an extrasellar component and 23% of them were associated with hydrocephalus. There was a significant difference in the recurrence-free survival rates between groups A-D [at 10 years: 100% (A), 100% (B), 38% (C) and 77% (D), P < 0.01], which persisted even when analysing patients operated after 1980. The median time of first recurrence was 2.5 years (range 0.5-36). The peri-operative mortality of the patients who had any type of neurosurgical intervention due to recurrence was higher than that observed after primary surgery (24%vs. 1.8%) (P < 0.01). The rate of re-accumulation of the cyst fluid was 58% during the first year in patients of group E, whereas none of the subjects of group F experienced such an event during their follow-up period. There was no reversal of pre-existing pituitary hormone deficits after any surgical intervention. The probabilities of GH, FSH/LH, ACTH, TSH deficiency and diabetes insipidus at the 10-year follow-up were 88%, 90%, 86%, 80% and 65%, respectively. After excluding the non-tumour-related deaths, the 10-year survival rate following presentation was 90%. Patients with recurrence had a significantly lower probability for survival compared with those without it (at 10 years: 70%vs. 99%, P < 0.01). At the 10-year follow-up the probability of the presence of major visual field defects was 48%, hyperphagia/obesity 39%, epilepsy 12% and hemi-/monoparesis 11%. In this large series no substantial differences in the outcome of tumours diagnosed during childhood or adult life were found. CONCLUSIONS: Craniopharyngiomas remain tumours associated with significant morbidity. Gross total removal provides favourable results in terms of recurrences. If this cannot be achieved safely, adjuvant radiotherapy is beneficial in preventing tumour re-growth. Childhood- and adult-onset lesions generally behave similarly.

Adolescent↗

PubMed2003

Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism.

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is an autosomal dominant disorder characterized by uniglandular or multiglandular parathyroid tumours that occur in the absence of other endocrine tumours. The disorder may represent either an early stage of multiple endocrine neoplasia type 1 (MEN1), or an allelic variant of MEN1, or a distinct entity involving another locus. We have explored these possibilities in seven families in whom primary hyperparathyroidism occurred as the sole endocrinopathy. METHODS: Seven FIHP families were ascertained and venous blood samples obtained from 35 members (17 affected and 18 unaffected) for DNA sequence analysis of the MEN1 gene. The mean (+/- SD) follow-up period in the 17 affected members was 15.06 (+/- 8.83) years. RESULTS: Four heterozygous germline mutations of the MEN1 gene were identified. These consisted of two 4-bp intragenic deletions that would result in prematurely truncated proteins, and two missense (Asp153Val and Ala411Pro) mutations. Furthermore, analysis of parathyroid tumour DNA from one individual revealed a loss of the wild-type allele and retention of the mutant allele, consistent with Knudson's 'two-hit' model of hereditary cancer and a tumour suppressor role for MEN1 in FIHP. CONCLUSIONS: Our results provide further support for FIHP being a distinct allelic variant of MEN1, and an analysis of the 16 mutations reported to date indicate that FIHP is associated with a higher frequency of missense MEN1 mutations.

Adenoma↗

PubMed2002

Coronary artery disease and dyslipidemia within Europe: genetic variants in lipid transport gene loci in German subjects with premature coronary artery disease.

Fifteen polymorphisms in six lipid transport genes were studied in a German population for relationships with dyslipidemia and coronary artery disease (CAD), to investigate a possible genetic basis for the marked differences in mortality rates from coronary heart disease within Europe. In other populations these polymorphisms have all been associated with CAD or with phenotypes known to predispose to CAD. The apoAI PstI polymorphism (P<0.005) and the lipoprotein lipase Ser(447)-Ter mutation (P<0.005) were associated with plasma triglyceride concentrations. Additionally, the apoAI PstI polymorphism (P<0.05), the apoB XbaI polymorphism (P<0.05) and apoE phenotypes (P<0.05) were associated with plasma cholesterol concentrations. However, none of the allele frequencies of the polymorphisms studied were related to the presence, or absence, of coronary artery disease. Associations between five polymorphisms representing four lipid transport gene loci and dyslipidemia were demonstrated in this German population. It is possible that predisposition to dyslipidemia in Germany involves a particular selection of polymorphic loci, which are different from those identified in other European countries.

Adult↗

PubMed2001

Linear growth characteristics of congenitally GH-deficient infants from birth to one year of age.

Birth length has been reported to be either normal or reduced in infants with congenital GH deficiency (CGHD). We evaluated 46 infants with CGHD followed in a single regional medical center. All were born full term and had peak GH of less than 10 microg/liter after provocative stimulation. Length SD score at birth was normal but subsequently showed deceleration, at 6 months and 12 months of age, before GH treatment. The majority were delivered vaginally (83%), and delivery was uncomplicated in 61%. Four patients (9%) had breech vaginal delivery. Perinatal morbidities were found in 72% of infants and included jaundice (n = 17), hypoglycemia with or without seizure (n = 14), and hypoxemia (n = 5). Multiple pituitary hormone deficiencies were found in 85% of the subjects. Organic lesions were documented in all 22 subjects who had magnetic resonance imaging and in 4 of 11 subjects who had computed tomography scan. Only the hypoglycemic infants received early GH treatment. Growth data in hypoglycemic and normoglycemic CGHD infants were not significantly different. In our population, CGHD did not adversely affect fetal growth but is essential for normal linear growth during early infancy. Congenital developmental abnormalities in the hypothalamic-pituitary region are the most common cause of CGHD and are best diagnosed by an magnetic resonance imaging study.

Aging↗

PubMed2001

Common genetic variants that relate to disorders of lipid transport in Spanish subjects with premature coronary artery disease.

Fifteen common polymorphic variants at six loci (apolipoproteins AI, B, CIII and E, hepatic lipase and lipoprotein lipase) involved in plasma lipid transport have been studied in 210 northern Spanish men, of whom 98 had proven coronary artery disease. The other 112 men were clinically free from coronary artery disease and acted as controls. The genotypes were investigated for relationships with plasma lipid and lipoprotein levels, as well as for the presence of coronary artery disease. As expected, the mean levels of plasma triacylglycerols (triglycerides) and lipoprotein (a) and the number of smokers were significantly higher in the disease group, and high-density lipoprotein (HDL)-cholesterol was significantly lower. Surprisingly, plasma cholesterol and low-density lipoprotein cholesterol were not different between the two groups. With regard to the common mutations, plasma triacylglycerol levels were related to the HindIII variants of lipoprotein lipase (P<0.05), to the apolipoprotein CIII variant (C3175G in exon 4) and to the apolipoprotein AI XmnI polymorphisms (P<0.05 and P<0.02 respectively). The apolipoprotein E variants were related to plasma cholesterol (P<0.05), HDL-cholesterol (P<0.02), plasma triacylglycerols (P<0.05) and the triacylglycerol/HDL ratio (P<0.01). Only the three-codon insertion/deletion variants of the apolipoprotein B signal peptide region discriminated between the two groups with or without arterial disease (P=0.02). The possible functional effects of these common mutations are discussed.

Adult↗

PubMed1998

Radiation dose and diagnosticity of barium enema examinations by radiographers and radiologists: a comparative study.

With the current emphasis on the extension of the role of the radiographer, radiographers in some hospitals now undertake some of the procedures traditionally performed by radiologists. In the present study, dose-area product (DAP) measurements for over 1000 barium enema examinations performed by radiologists and radiographers were analysed and compared to ascertain whether there were significant differences in the radiation dose to the patient, depending on the category of staff performing the examination. All examinations were reported by a radiologist. The radiologist's reports were analysed against the known outcomes to compare the diagnosticity of the examination when carried out by the two categories of staff. The study shows that although radiographers are able to produce consistent diagnostic results, there is an increase in patient dose due to extra films taken for reporting, which may be difficult to justify. Measures for reducing the dose from this component of the examination were explored.

Aged↗

PubMed1995

Common genetic variants of lipoprotein lipase that relate to lipid transport in patients with premature coronary artery disease.

Two common coding sequence mutations of lipoprotein lipase (serine447-ter, producing a carboxy terminal truncation; and asp9-asn variants) were studied in 329 Caucasian subjects, of whom 243 had angiographic features of premature atheroscelerosis (220 with coronary artery disease; 23 with coronary and peripheral artery disease). As expected, the mean levels of cholesterol, triglycerides, LDL-cholesterol, ApoB and Lp(a) were significantly higher in the arterial disease group than in the controls. HDL levels were lower in the patient group. With regard to the common mutations, plasma triglycerides and VLDL-triglycerides were lower in subjects possessing the Serine447-Ter mutation (p = 0.06 and < 0.05, respectively). When the lipid distributions were analysed by tertiles, the Ser447-Ter mutation was significantly less frequent in the highest tertiles for triglycerides (p < 0.02), and VLDL (p < 0.04). The Asp9-Asn substitution was significantly more frequent in the lowest tertiles for ApoAI (p = 0.05). Case-control analyses of genotypic distributions between the two groups with or without arterial disease did not show any significant differences. The possible functional effects of these common mutants of lipoprotein lipase are discussed.

Asparagine↗

PubMed1994

Mortality in multiple trauma patients with fractures.

A multicentered study was performed to determine the mortality rate of patients with multiple injuries with major pelvic and long bone fractures who have early total care of their injuries. A 2-year review of patients with ISSs > or = 18 with major fractures treated at the trauma centers in Buffalo, New York, Camden, New Jersey, Nashville, Tennessee, Baltimore, Maryland, Tampa, Florida, and Seattle, Washington was performed. This group of 676 patients was compared with a similar group of 906 patients from the American College of Surgeons' Multiple Trauma Outcome Study. Mortality was significantly reduced in the patients who had early total care of all their injuries including fracture stabilization for patients less than 50 years of age and those 50 years and older. In a subgroup of patients less than 50 years of age and an ISS of 18-34 and 35-45 there was a mortality reduction from 11.8% to 5.1% and from 25.8% to 11.5%, respectively, when the fractures were managed acutely. Similar reductions in mortality were found in the patients 50 years of age and older with early fracture stabilization with a reduction from 26.4% to 8% in patients with ISSs of 18-24 and a reduction from 42.3% to 18.4% in the patients with ISSs of 35-45. This study clearly shows the additional benefit of early fracture stabilization in reducing mortality rates in the patient with multiple injuries.

Adult↗

PubMed1991

C reactive protein and immunoglobulin G in synovial fluid and serum in joint disease.

C reactive protein (CRP) and immunoglobulin G (IgG) were measured in synovial fluid and serum of 72 patients (29 with rheumatoid arthritis (RA), 17 with osteoarthritis, 11 with crystal synovitis, seven with undifferentiated arthritis, and eight with seronegative arthritis). The synovial fluid:serum (SF:S) ratios were compared with those calculated from the SF:S ratios of transferrin, caeruloplasmin, and alpha 2 macroglobulin, using the binomial test within groups and the Mann-Whitney test between groups. In RA synovial fluid CRP concentrations were lower than expected and IgG concentrations higher than expected. In osteoarthritis CRP concentrations were higher than expected. In seronegative arthritis IgG concentrations were raised. The ratio of CRP:IgG was depressed in RA. These findings are consistent with a role for CRP in the inflammatory process of RA, while the CRP:IgG ratio may be of value in the differential diagnosis of joint disease.

Arthritis↗

PubMed1990

Association between Graves' ophthalmopathy and smoking.

Patients with Graves' disease were questioned by postal survey about their smoking history. There were significantly more smokers in the group with ophthalmopathy than in the group with Graves' thyrotoxicosis or controls. Patients with severe eye signs smoked significantly more tobacco than did those with less serious signs.

Adult↗

PubMed1990

Antilens antibodies in cataract and inflammatory eye disease: an evaluation of a new technique.

A new technique measuring serum antoantibodies to lens proteins, employing antigen linked to magnetisable cellulose particles and fluorescent end-point detection, was used to examine patients with senile cataract and inflammatory eye disease. 40% of patients with senile cataract had antibodies to lens proteins, as did 28% of patients with heterochromic cyclitis and 20% of patients with uveitis, while there were no positive sera from patients with scleritis. The single patient with lens-induced uveitis had a high titre, but so did some patients with senile cataract. With the incorporation of a standard curve this technique offers a reliable quantitative assay for lens autoantibodies. It may provide a valuable tool for the investigation of pathogenetic mechanisms in cataract and inflammatory eye disease.

Autoantibodies↗

PubMed1990

Analysis of HLA-DQB and HLA-DPB alleles in Graves' disease by oligonucleotide probing of enzymatically amplified DNA.

We have tested the possible association of HLA-DQB and HLA-DPB alleles with Graves' thyrotoxicosis, with or without severe ophthalmopathy, by polymerase chain amplification of genomic DNA and allele-specific oligonucleotide probing. There was no significantly abnormal distribution of DQB alleles compared to 50 control subjects except for a reduced prevalence of DQw 3.1 in the Graves' patients with severe ophthalmopathy (X2 = 6.23, P less than 0.02). HLA-DPB 2.1/8 was found in only 1 of 40 of these patients compared with 15 of the controls (X2 = 11.49, P less than 0.001). Ten of 48 patients with Graves' disease but without clinically significant eye involvement were HLA-DPB 2.1/8 positive, not significantly different from controls, but significantly different from the ophthalmopathy group (X2 = 6.70, P less than 0.01). The other DPB alleles in both groups of Graves' disease patients were the same as controls. These results suggest that HLA-DPB 2.1/8 may confer a protective effect in Graves' disease with respect to ophthalmopathy.

Alleles↗

PubMed1990

Thyroid-stimulating antibody activity between different immunoglobulin G subclasses.

To investigate the distribution of thyroid-stimulating antibody (TSAb) activity between IgG subclasses, sera from 11 patients with Graves disease (including the National Institute of Biological Standards and Control (NIBSC) Research Standard, long acting thyroid stimulator-B) were fractionated by chromatography on affinity columns of monoclonal IgG subclass antibodies or protein A to deplete all but a single subclass. The resulting fractions were 98% or more pure for a single subclass. In all 11 patients, TSAb activity appeared to be confined to the IgG1 fraction as determined by cAMP production on addition of the fractions to the FRTL-5 rat thyroid cell line. In all of eight specimens from seven patients so tested, the whole serum activity was recovered in the IgG1 fraction, after adjusting for the recovery of the isotype from the column. TSAb activity in one serum comprised both lambda and kappa light chains but was IgG1 restricted. This IgG subclass restriction was not found when the same fractions were tested for thyroglobulin, microsomal/thyroid peroxidase, or tetanus toxoid antibody activity. Together with previous results showing marked restriction of both light chain usage and isoelectric point of TSAb, these results support the idea that Graves' disease may be the result of an oligo- or possibly monoclonal response at the B cell level.

Cyclic AMP↗

PubMed1989

T and B cell reactivity to extraocular and skeletal muscle in Graves' ophthalmopathy.

We have sought human eye muscle membrane binding antibodies in patients with Graves' ophthalmopathy using an enzyme-linked immunoassay. Antibodies were found in patients with thyroid autoimmunity irrespective of eye signs, and binding correlated closely (r = 0.94) with binding to skeletal muscle, showing that these antibodies are not site-specific. T cells from patients with thyroid autoimmunity proliferated in response to eye muscle, but again this was not specific for eye muscle or the presence of ophthalmopathy. No single antigen was responsible for inducing proliferation. These results fail to confirm a recent report of eye muscle membrane binding antibodies in a high proportion of patients with ophthalmopathy, and suggest instead that T and B cell autoreactivity to striated muscle antigens is a frequent feature of autoimmune thyroid disease, unlikely to be directly related to eye disease.

Adolescent↗

PubMed1989

Immunohistochemical analysis of the retrobulbar tissues in Graves' ophthalmopathy.

We have characterized the mononuclear cell infiltrate in the extraocular muscle of three patients with Graves' disease, using antibodies which permit staining of paraffin-embedded tissue. The majority of lymphocytes, occurring in foci or interstitially, were T cells, most of which stain for CD3 or with UCHL1. T cells few, if any, stained with SN130, directed against the CD45R determinant. This suggests that these lymphocytes comprise a recently activated population within which memory cells may reside. B cells were also found but were predominantly confined to focal aggregates, and in one patient lymphoid follicles were seen. The orbital fat and connective tissue from a further two patients contained very few infiltrating cells which were mainly UCHL1-positive. Eye muscle cells did not express Ia antigens but the interstitial cells between them were Ia-positive and the vascular endothelium in four of the five specimens also stained with Ia. These results indicate that Graves' ophthalmopathy is associated with T cell, and to a lesser extent B cell, responses against the retrobulbar tissues; the extraocular muscle interstitial cells, probably including fibroblasts, may be targets of activation resulting from this infiltration.

Adult↗

PubMed1988

Immunogenetics of Graves' ophthalmopathy.

We have performed an immunogenetic analysis of 53 patients with severe Graves' ophthalmopathy, 51 patients with Graves' disease but little or no clinically apparent eye disease, and 90 controls. The distribution of restriction fragment length polymorphisms was analysed in the three groups, using probes for the HLA-DQ alpha and DR beta regions, the T-cell receptor C alpha, V alpha, C beta and J gamma genes and the immunoglobulin gene switch regions, S alpha and S mu. There was no abnormal distribution of these polymorphisms in either group of Graves' patients, or differences between the Graves' patients with or without eye disease. It was possible to assign HLA-DR types in most patients using the polymorphisms found after probing with DQ alpha and DR beta; there was no abnormal distribution of DR types (including HLA-DR3) assigned by restriction fragment polymorphisms in the two Graves' groups. These results fail to confirm the reported associations between ophthalmopathy and HLA-DR3 and between Graves' disease and the T-cell receptor C beta polymorphism; they also argue against a strong influence of Gm allotypes in Graves' disease since these genes are in linkage disequilibrium with the S alpha polymorphisms. The association of Graves' disease with HLA-DR3, defined hitherto using serological reagents, may be less strong than previously described.

Graves Disease↗

PubMed1988

Management of dysthyroid eye disease.

Once the diagnosis of thyroid eye disease has been made the doctor's problems begin because the management is long term with a condition that has many ramifications over a period of years. Short-term heroics to save vision by use of high-dose systemic steroids, orbital decompression or radiotherapy may have to be followed by control of diplopia by muscle surgery and prisms. Lid retraction, both upper and lower, may merit surgery, and even those patients who have come to terms with their facial appearance may still complain of lacrimation, irritation and grittiness. The advantages of a thyroid clinic, run jointly by a physician and an ophthalmologist, are presented and the patient is helped to live with this distressing condition.

Adult↗

PubMed1988

Kappa/lambda immunoglobulin distribution in Graves' thyroid-stimulating antibodies. Simultaneous analysis of C lambda gene polymorphisms.

From patients with untreated Graves' disease 11 sera showing high cAMP release in the FRTL-5 cell assay were studied for relative proportions of kappa or lambda Ig molecules showing cAMP releasing activity. Immunoabsorption of gamma-globulins was performed using monoclonal murine anti-kappa or anti-lambda antibodies linked to cyanogen bromide-activated sepharose. Specific kappa- or lambda-adsorbed fractions were also eluted from immunoabsorbents using chaotrophic thiocyanate buffers and equilibrated with pH 7.4 low salt buffer by dialysis. Immunoabsorption and elution experiments showed that five Graves' sera contained predominant cAMP-releasing activity within lambda Ig fractions, whereas two Graves' sera showed predominant cAMP-releasing activity in kappa Ig fractions. Four sera showed cAMP release approximately equally divided between kappa and lambda Ig both after immunoabsorption and specific anti-kappa or anti-lambda eluates were studied. C lambda genotypes were examined by Southern blotting and restriction fragment length polymorphism analysis of Eco RI-digested genomic DNA from 158 patients with Graves' disease in parallel with 112 normal controls and 29 patients with autoimmune hypothyroidism. Notable shifts in proportions of 8/8 and 18/18 genotypes were present when Graves' patients were compared with normal controls. Allelic frequencies and ratios of genotype 8 to 18 were significantly different (P less than 0.05) when Graves' patients were compared either to normal controls or to patients with autoimmune hypothyroidism.

Absorption↗