bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell Vβrepertoires in childhood vasculitides
Authors: BROGAN P A , SHAH V , BAGGA A , KLEIN N , DILLON M J 
Published: March 2003

SummarySuperantigens (SAgs) are potent stimulators of T cells bearing specific Vβ T cell receptors (TCR) and may play a role in the aetiopathogenesis of systemic vasculitis, although this remains contentious. To investigate the possible aetiological role of SAgs, this study examined peripheral blood T cell Vβ repertoires in children with systemic vasculitis. FACS analysis of 17 different peripheral blood T cell Vβ families was performed in 20 healthy control children, 27 disease control children with nonvasculitic inflammatory disease, 25 children with primary systemic vasculitis, six patients with Kawasaki disease (KD) and six patients with Henoch–Schönlein purpura (HSP). There was a significantly increased variance of CD4 Vβ12 and Vβ17, and CD8 Vβ1 in the primary systemic vasculitis group compared to control and disease controls. Moreover, 80% of the primary systemic vasculitis children had one or more CD4 Vβ expansions or deletions, compared with 30% of controls (P &lt; 0·002), and 37% of the disease controls (P &lt; 0·002). In the KD group, the mean percentage of CD4 Vβ2 T cells was higher than in controls or disease controls. In the HSP group, there was no consistent skewing of the T cell Vβ repertoire. We have observed changes in the T cell Vβ repertoire in children with vasculitis over and above those observed in disease controls. While these data provide impetus for further research into this contentious field, they do not resolve unequivocally the question of the role of SAgs in childhood vasculitic syndromes.
Streptococci andActinomycesinduce antibodies which cross react with epithelial antigens in periodontitis
Authors: YE P , HARTY D W S , CHAPPLE C C , NADKARNI M A , CARLO A A D E , HUNTER N 
Published: March 2003

SummaryPerturbation of epithelial structure is a prominent but poorly understood feature of the immunopathological response to bacterial antigens which characterizes the destructive lesion of periodontitis. Western analysis of sera from 22 patients with periodontitis detected multiple antigens in extracts of epithelial cells whereas sera from 12 periodontally healthy subjects displayed only trace reaction with epithelial antigens. To investigate a possible relationship between the bacterial flora adjacent to diseased sites and the presence of antibodies reactive with epithelium, subgingival plaque samples were taken from deep periodontal pockets and cultured anaerobically. Gram positive bacteria containing antigens cross-reactive with epithelial cells were reproducibly isolated by probing membrane colony-lifts with affinity-isolated (epithelium-specific) antibodies and identified by 16S rDNA sequence homology as streptococci (S. mitis, S. constellatus and two S. intermedius strains) and Actinomyces (A. georgiae, and A. sp. oral clone). Conversely, when serum from patients with periodontitis was absorbed with the captured bacterial species the number of epithelial antigens recognized was specifically reduced. It was concluded that development of cross-reactive antibodies related to these organisms may contribute to perturbation of the epithelial attachment to the tooth and the progression of periodontitis. These autoreactive antibodies could also be a contributing factor in other diseases affecting epithelia.
Development of hyperandrogenism during treatment with insulin‐like growth factor‐I (IGF‐I) in female patients with Laron syndrome
Authors: Klinger  , Anin  , Silbergeld  , Eshet  , Laron  
Published: March 2003

OBJECTIVEPatients with Laron syndrome (LS) can now be treated with recombinant IGF‐I. We describe the development of androgenization during IGF‐I treatment of female LS patients.PATIENTSSix female patients with LS—two clinically prepubertal (11.6 and 13.8 years of age) and four young adults (30 to 39 years old)—underwent long‐term replacement treatment with recombinant IGF‐I. The daily doses were 150 μg/kg/day by subcutaneous (s.c.) injection in the girls and 120 μg/kg/day in the adult women.METHODSTestosterone, Δ4‐androstenedione, LH, FSH, insulin and IGF‐I were determined by radioimmunoassay. Blood samples were obtained after an overnight fast before the IGF‐I injection. Serum IGF‐I was also determined 4 hours after the s.c. injections.RESULTSDuring IGF‐I treatment, four out of the six patients (two girls and two adults) developed progressive clinical symptoms and signs of hyperandrogenism (oligo/amenorrhoea and acne). Laboratory determinations showed a significant elevation in serum testosterone, Δ4‐androstenedione and LH/FSH ratio. The hyperandrogenism occurred concomitantly with an increase in IGF‐I serum and a decrease in serum insulin concentrations. Reduction in IGF‐I dose or interruption in IGF‐I treatment restored androgen levels to normal values. At the same time, the acne and oligomenorrhoea resolved.CONCLUSIONSOverdosage of IGF‐I can lead to androgenization, a previously undescribed undesirable effect of IGF‐I. Long‐term IGF‐I treatment necessitates progressive adjustment of the IGF‐I dose to avoid overtreatment.
The development of the foetal thyroid: in utero ultrasonographic measurements
Authors: Achiron Reuwen , Rotstein Zeev , Lipitz Shlomo , Karasik Avi , Seidman Daniel S. 
Published: March 2003

OBJECTIVEThe early recognition of potentially treatable thyroid disease in the foetus frequently depends on the detection of abnormal growth of the foetal thyroid gland. We have therefore established nomograms for foetal thyroid transverse width and circumference from 14 weeks of gestation until term, using transvaginal and transabdominal high‐resolution ultrasound techniques.DESIGNA prospective, cross‐sectional study of 193 normal singleton pregnancies was performed.MEASUREMENTSThyroid size was measured by transvaginal ultrasonography between 14 and 17 weeks, and by abdominal ultrasound from 18 to 37 weeks of gestation.RESULTSData was accurately obtained for 193 foetuses. The mean ± SD thyroid width and circumference were 11.7 ± 4.1 mm (95% confidence interval 11.1–12.3) and 39.5 ± 14.1 mm (95% confidence interval 37.4–41.6), respectively. Thyroid size as a function of gestational age was expressed by the regression equations: thyroid width (mm) =−3.94 + 0.68 × gestational age (weeks), and thyroid circumference (mm) =−1.38 + 0.23 × gestational age (weeks). The correlation coefficients, r = 0.91 and r = 0.93, for thyroid width and circumference, respectively, were found to be highly statistically significant (P < 0.0001). The normal mean of thyroid width and circumference for each week of gestational age and the 95% prediction limits were defined.CONCLUSIONSThe present data offer normative measurements of the foetal thyroid that may facilitate the prenatal diagnosis of foetal goitre and make early administration of in utero treatment possible.
Amelioration of polyuria in nephrogenic diabetes insipidus due to aquaporin‐2 deficiency
Authors: Hochberg Ze’ev , Even Lea , Danon Abraham 
Published: March 2003

OBJECTIVEWe have recently reported a large cluster of patients with nephrogenic diabetes insipidus (NDI) due to an autosomal recessive aquaporin‐2 (AQP‐2) early‐stop codon. This paper describes the clinical manifestations and evaluation of therapeutic approaches to this new entity.PATIENTS AND DESIGNNine patients with an AQP‐2 mutation were studied. Urine osmolality was measured in five patients before and at 3 × 30 min intervals after desmopressin given in increasing doses of 5–100 μg. Urinary prostaglandins PGE2 and 6‐keto PGF1α, were extracted from 24‐h urine samples and estimated by radioimmunoassays. Eight NDI patients were given a combination of a low‐sodium diet and hydrochlorothiazide. Four to 11 weeks later, ibuprofen was added, and the patients were retested within the following 4–9 weeks.RESULTSUrine osmolality remained unchanged after supra‐pharmacological doses of desmopressin, at 60–70 mOsm/kg. Urinary PGE2 in control subjects was 0.74 ± 0.1 μg/g creatinine (mean ± SD) compared to 5.0 ± 2.6 μg/g creatinine in AQP‐2 deficient patients (P < 0.05). Urinary 6‐keto PGF1α, was 0.20 ± 0.03 μg/g creatinine in controls and 0.75 ± 0.31 μg/g creatinine in AQP‐2 deficiency (P < 0.05). Urinary volumes decreased by a mean 31% on a low‐salt diet and hydrochlorothiazide, and by a mean of 38% on the combination therapy. Plasma osmolality decreased by a mean 15 mOsm/kg on the low‐salt diet and hydrochlorothiazide, and by 22 mOsm/kg on the combination therapy. Urinary osmolality increased from a mean 80 mOsm/kg to 96 mOsm/kg on the low‐salt diet and hydrochlorothiazide, and to 146 mOsm/kg on the combination therapy.CONCLUSIONAQP‐2 deficiency in these patients with an early‐stop codon is associated with complete unresponsiveness of the collecting duct to vasopressin, implying an indispensable role for AQP‐2 in vasopressin antidiuresis. Urinary PGE2 and 6‐keto PGF1α are elevated, the former being extremely high, apparently due to the extreme vasopressin unresponsiveness. Combination therapy with a combination of a low‐salt diet, thiazide and non‐steroidal anti‐inflammatory drug is partially effective.
Cortisol in dried blood screening specimens from newborns with raised 17‐hydroxyprogesterone and congenital adrenal hyperplasia
Authors: Mitchell Marvin L. , Hermos Rosalie J. 
Published: March 2003

BACKGROUND AND OBJECTIVEScreening for congenital adrenal hyperplasia (CAH) in newborns has become a routine part of many programmes by measuring levels of 17 α‐hydroxyprogesterone (17‐OHP) in the newborn filter‐paper blood specimen. Unfortunately, raised levels of 17‐OHP, which are largely the consequence of cross‐reacting metabolites, are also found in low birth weight, premature and ill neonates. We speculated that differences in concen_trations of cortisol in the newborn screening specimen would aid in distinguishing between CAH positive and CAH negative infants among those with raised levels of 17‐OHP.DESIGNComparison of cortisol concen_trations was made between newborns with CAH and those without but with raised 17‐OHP levels.PATIENTSNewborn filter‐paper blood specimens from 31 infants with transient 17‐OHP elevations and 16 infants with confirmed CAH were analysed for cortisol. In addition, assay performance was validated by comparing cortisol values obtained from dried whole blood on filter‐paper with the corresponding plasma from 31 adults and six neonates.MEASUREMENTSCortisol in filter‐paper blood specimens was determined by adapting a commercial radioimmunoassay kit that had been designed for the determination of cortisol in serum.RESULTSThe mean cortisol level in the CAH negative group was significantly higher than the mean value in the group with documented CAH (means 1190 ± 795 nmol/l vs 627 ± 210 nmol/l; P < 0.01). However, approximately half of the CAH negative infants had cortisol values that overlapped those from the CAH positive group. There was no relationship between the magnitude of the 17‐OHP elevation and cortisol concen_trations.CONCLUSIONThe measurements of cortisol in dried blood on filter‐paper using a commercial radioimmunoassay kit has been shown to be reliable and simple to carry out. The level of cortisol in newborn blood specimens can be used to exclude some infants with elevated 17α‐hydroxyprogesterone levels from further testing for CAH. However, overlapping cortisol values between CAH positive and negative infants precludes the assay of cortisol from being used routinely as a reliable means of decision making.
Growth hormone status in adults treated for acute lymphoblastic leukaemia in childhood
Authors: Brennan  , Rahim  , Mackie  , Eden  , Shalet  
Published: March 2003

OBJECTIVEGrowth hormone status was assessed in a cohort of 32 (16 male) adults who had received cranial irradiation (XRT) in childhood as part of their treatment for acute lymphoblastic leukaemia (ALL) and compared with 35 age matched young adults (18 male).DESIGNHeight and weight were measured in all subjects and the heights of the patients at XRT were obtained from their case notes. Each patient and control underwent two provocative tests of growth hormone (GH) secretion using insulin (0.2 IU/kg body weight) and arginine (20 g/m2). Basal serum insulin like growth factor‐1 (IGF‐1) and IGFBP‐3 (binding protein‐3) concen_trations were also measured.RESULTSThe patient group had a significantly lower peak GH response to both provocative tests (P < 0.01), and lower IGF‐1 and IGFBP‐3 levels compared with the normal controls (P < 0.01). Nine of the patient group were severely GH deficient (peak GH response <9 mU/l to both provocative agents) and a further 12 patients were GH insufficient (peak GH response <20 mU/l to both tests with at least one peak GH response >9 mU/l). Overall a significant median change in height from XRT to final height of −0.5 SDS was found which was even greater in the severely GH deficient group (median change in height of −2.1 SDS).CONCLUSIONThese data suggest that a significant proportion of adults treated with cranial XRT in childhood with irradiation doses between 18–25 Gy, as part of their treatment for ALL, are severely GH deficient now and should be considered for GH replacement. Changes in GH secretion evolve with time following irradiation‐induced damage to the hypothalamic‐pituitary axis; therefore long‐term surveillance will be required in those remaining patients, in whom GH status is considered currently to be insufficient or even normal.
Growth hormone treatment improves body fluid distribution in patients undergoing elective abdominal surgery
Authors: Møller  , Jensen  , Frandsen  , Møller  , Kissmeyer  , Laurberg  
Published: March 2003

OBJECTIVETo investigate the possible beneficial effects of growth hormone (GH) in catabolic patients we examined the impact of GH on body fluid distribution in patients with ulcerative colitis undergoing elective abdominal surgery.DESIGN AND MEASUREMENTSTwenty‐four patients (14 female, 10 male) aged 19–47 years were in a double‐blinded study randomly assigned to receive either placebo (n = 12) or GH (n = 12) 6IU s.c. twice daily from 2 days before until 7 days after ileo‐anal J pouch surgery. Extracellular and plasma volume (ECV, PV) were determined using 82Br and 125I albumin dilution at day −2 and at day 7, and body composition was estimated by dual X‐ray absorptiometry and bioimpedance. Changes in body weight and fluid balance were recorded and hence intracellular volume was assessed.RESULTSDuring placebo treatment body weight decreased 4.3± 0.6 kg; during GH treatment body weight was constant (P < 0.01). There was a positive fluid balance in the GH‐treated patients compared to the placebo group (GH: 3.6 ± 0.7 l; plc: −0.7 ± 1.2 l, P < 0.01). ECV increased 2.12 ± 0.70 l during GH and was unaffected during placebo (P = 0.02). PV was unchanged by GH and decreased 0.39 ± 0.08 l during placebo administration (P = 0.03). Intracellular volume (ICV) decreased less during GH than during placebo (GH: −1.42 ± 0.45; plc: −3.70 ± 0.76; P = 0.02). Bioimpedance remained constant during GH administration and increased 60 ± 9 ohm in the placebo‐treated group (P < 0.05). Plasma renin and aldosterone remained unchanged in both study groups.CONCLUSIONBody weight, plasma volume and intracellular volume is preserved during GH treatment in catabolic patients and ECV is increased. From a therapeutic point of view these effects may be desirable under conditions of surgical stress.
Serum prolactin concentration in patients taking neuroleptic drugs
Authors: Pollock Anne , McLaren E. H. 
Published: March 2003

OBJECTIVENon‐tumour causes of hyperprolactinaemia, including prolactin‐elevating drugs, must be excluded. There is a general view that such drugs are unlikely to raise serum PRL above 3000 mU/l, but the literature is confusing. We report 8 patients receiving treatment with neuroleptic drugs, whose serum PRL concentrations were grossly elevated.METHODSProlactin was measured using a 2‐site immunofluorometric assay (Abbott Laboratories; reference range < 500 mU/l). Seven of the eight women (age range 24–49 years) were symptomatic (galactorrhoea, oligo‐ or amenorrhoea).RESULTSProlactin concentrations ranged from 3600 mU/l to 7300 mU/l. All patients had a normal pituitary CT scan. Five patients were treated with bromocriptine without detriment to their mental state.CONCLUSIONProlactin can rise to concentrations associated with prolactinomas in patients on neuroleptic drugs. As it is rarely possible to stop the drugs to see if the PRL concentration will decline to normal, neuroradiology is required in these patients to exclude a vision‐threatening macroprolactinoma before deciding on medical treatment.
Dual facets of hyponatraemia and arginine vasopressin in patients with ACTH deficiency
Authors: Yamamoto Toshihide , Fukuyama Jiro , Kabayama Yasuhiro , Harada Hiromasa 
Published: March 2003

OBJECTIVEHyponatraemia is often observed in patients with ACTH deficiency who are thought not to suffer from volume depletion. Their high plasma AVP levels relative to plasma osmolality are presumed to be maintained by non‐osmotic mechanisms. We attempted to assess volume status from changes in selected clinical measurements related to body fluid balance in the course of i.v. fluid supplementation and following glucocorticoid (GC) replacement in ACTH‐deficient patients, and to interpret plasma AVP levels in the context of the estimated volume status.PATIENTS AND DESIGNThis report consists of three parts. First, an ACTH‐deficient patient with hyponatraemia and volume depletion who was followed through volume replacement to recovery after GC replacement is described (case report). Secondly, medical records of five ACTH‐deficient patients with hypovolaemia and hyponatraemia were surveyed retrospectively to observe changes in serum levels of sodium, uric acid (UA) and haematocrit (Hct) following i.v. fluid supplementation of low sodium content (retrospective study). Thirdly, five ACTH‐deficient patients with or without overt dehydration were studied with regard to body weight, blood pressure, serum sodium, total proteins, Hct and blood urea nitrogen before and after GC replacement (prospective study). Plasma AVP levels were measured after i.v. fluid supplementation without GC replacement in the patients of the retrospective study, and before and after GC replacement in the patients of the prospective study.RESULTSThe first patient became more hyponatraemic after i.v. fluid supplementation and recovered ultimately from hyponatraemia after GC replacement. In five patients studied retrospectively, the serum sodium levels fell progressively following i.v. fluid supplementation, concurrent with reduction in UA levels and Hct, which indicated the dilutional nature of the hyponatraemia. In the patients observed prospectively, the accumulation of fluid and sodium was indicated by a rise in body weight, blood pressure and serum sodium levels and a decline in Hct and total proteins after GC replacement. Plasma AVP levels rose similarly in patients with dilutional hyponatraemia and in patients with borderline hyponatraemia before GC replacement.CONCLUSIONPatients with untreated ACTH deficiency may have either of two kinds of hyponatraemia—i.e. borderline hyponatraemia associated with subclinical hypovolaemia, or dilutional hyponatraemia. Similarity of plasma AVP levels in two hyponatraemic states suggests their AVP secretion is regulated by nonosmotic, non‐volume mechanisms, possibly released from GC suppression at low plasma osmolality.
Oestrogen has no short‐term effect on intestinal strontium absorption in healthy postmenopausal women
Authors: ten Bolscher Marieke , de Valk‐de Roo Gerdien W. , Barto Rob , van der Vijgh Wim J. F. , Netelenbos J. Coen 
Published: March 2003

OBJECTIVEImpaired intestinal calcium absorption in postmenopausal women is often indirectly linked to decreased serum 1,25(OH)2D or to intestinal resistance to its action rather than directly to low circulating oestrogen levels following the menopause. The purpose of this clinical study was to investigate the short‐term effect of oral 17β‐oestradiol on intestinal calcium absorption, with strontium as a marker.DESIGN AND PATIENTSTwenty‐five healthy postmenopausal women participated in this randomised double blind placebo controlled clinical trial. Twelve women received oestradiol therapy (2 mg/day) and thirteen placebo for 2 months. Fractional strontium absorption (Fc240) was assessed at baseline and after 2 months of oestradiol/placebo therapy.RESULTSIntestinal strontium absorption (Fc240) was unchanged after treatment with 17β‐oestradiol (10.1 ± 5.0 vs. 10.2 ± 3.8 (%)). Serum total calcitriol (1,25(OH)2 D) was unchanged after treatment with placebo (88 ± 22 vs. 79 ± 21 (pmol/l)) but increased after treatment with oestradiol (88 ± 30 vs. 116 ± 33 (pmol/l); P < 0.005). Serum vitamin D binding protein (DBP) increased after oestradiol but not after placebo treatment. The free serum 1,25(OH)2D index was calculated. This index did not change after oestrogen therapy (1.6 ± 0.5 vs. 1.8 ± 0.5).CONCLUSIONIn healthy postmenopausal women, short‐term suppletion with exogenous oral oestrogen did not influence intestinal calcium absorption as measured by the strontium absorption test.
Familial non‐medullary thyroid carcinoma: pathology review in 27 affected cases from 13 French families
Authors: Leprat  , Bonichon  , Guyot  , Trouette  , Trojani  , Vergnot  , Longy  , Belleannée  , De Mascarel  , Roger  
Published: March 2003

BACKGROUND AND OBJECTIVESWhen familial non‐medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC.PATIENTS AND METHODSThirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 ± 16 years; mean ± SD) was ‘siblings’ in eight families, ‘parent and child’ in four and ‘aunt and niece’ in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 ± 11 mm) was performed.RESULTSinitial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 ± 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative ‘familial’ phenotype of FNMTC, this may be fortuitous.CONCLUSIONMicro familial non‐medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non‐medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue.