bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly
Authors: Jenkins D. , O'Brien I. , Johnson A. , Shakespear R. , Sheppard M. C. , Stewart P. M. 
Published: March 2008

SummaryBACKGROUND Reduction of GH concentrations in acromegalic subjects may improve the increased mortality associated with the condition. Audit of the biochemical outcome of the management of acromegaly is, therefore, important.OBJECTIVES (1) To audit the biochemical ‘cure’ rate of acromegalic patients treated by surgery and/or radiotherapy under the care of the South Birmingham Endocrine Clinic. (2) To assess the correlation between random or basal GH with IGF‐I and nadir GH during an oral glucose tolerance test.DESIGN AND MEASUREMENTS Ascertainment Of acromegalic patients from a pituitary database. Mode of therapy, pretreatment GH, pretreatment tumour size, post‐treatment GH, post‐treatment IGF‐l and post‐treatment nadir GH were recorded. Biochemical cure was defined as a most recent random or basal GH < 5 mU/l. Cure rates were determined.PATIENTS Eighty‐nine acromegalic patients were Identified as having received surgery and/or radiotherapy. In 35/89 (39%) the most recent GH was < 5 mU/l. The cure rate following surgery was 26/78 (33%). This was not significantly associated with tumour size, but was associated with pretreatment GH concentration (x2= 7.1, 2d.f., P < 0.05). Random/basal GH showed a log‐linear association with IGF‐I, r= 0.72, and a linear association with nadir GH, r = 0.93.CONCLUSIONS Biochemical cure of acromegaly was more strongly associated with pretreatment GH than with tumour size. Random/basal GH measurements are useful and convenient for the audit of treatment outcome in acromegaly. Ways of improving the biochemical outcome of acromegaly should be sought.
A study of untreated Graves' patients with undetectable TSH binding inhibitor immunoglobulins and the effect of anti‐thyroid drugs
Authors: Kawai K. , Tamai H. , Matsubayashi S. , Mukuta T. , Morita T. , Kubo C. , Kuma K. 
Published: March 2008

SummaryOBJECTIVE We previously reported the clinical characteristics of Graves' disease with undetectable TSH binding inhibitor immunoglobulins (TBII) at first visit, but a study of the prognosis of untreated TBII negative patients with anti‐thyroid drug medication has never been undertaken. The aim of this paper is to study the difference between negative and positive TBll Graves' disease in relation to the effect of anti‐thyroid drug treatment.PATIENTS From January 1986 to April 1991,1545 patients with untreated Graves' disease were referred to Kuma Hospital, Kobe, Japan. Of these, 94 TRAb negative patients were identified. Another 83 TRAb positive patients were randomly selected from the other Graves' disease patients and served as a comparison group. Fifty‐six of the 94 patients in the TBII negative group and 52 of the 83 patients in the TBII positive group completed treatment with methimazole only.MEASUREMENTS The trial was conducted as a retrospective study with a maximum treatment period of 36 months and a follow‐up period of a further 12 months. From the original pool of patients, we classified 56 TBII negative patients into two groups according to the clinical course taken; Group A in whom TBII remained undetectable throughout methimazole treatment (9 men and 34 women, age 37.2 ± 2.2 years), and Group B who became TBII positive (4 men and 9 women, 31.2 ± 44 years). Fifty‐two TBII positive patients served as the comparison Group C (8 men and 44 women, age 38.1 ± 2.0 years).RESULTS Serum free T4 and free T3 levels in groups A and B were significantly lower before treatment than those of Group C (P < 0.001). The thyroid volumes of Group A and B patients were significantly smaller than those of Group C (P < 0.01). The level of TBII in Groups A and B was significantly lower than that in Group C (8.3 ± 0.7 and 8.8·1.1 vs 57.0 ± 28%, respectively, P < 0.001). The level of thyroid stimulating antibody (TSAb) in Groups A and B was significantly lower than that in Group C (478 ± 71.0 and 761 ± 140.3 vs 2143 ± 280%, respectively, P < 0.01), and there were no significant differences in TSAb activities between Groups A and B. The remission rates in Groups A, B and C were 77.4, 36.4 and 36.5%, respectively. These data Indicate that Group A has a good prognosis, but Group B has the same prognosis as Group C.CONCLUSION We conclude that patients In whom TSH binding inhibitor Immunoglobulins remained negative have a much better prognosis than TSH binding inhibitor immunoglobulins positive patients or those who become TSH binding inhibitor immunoglobulins positive, having been initially negative.
Treatment of post‐menopausal osteoporosis with a combination of growth hormone and pamidronate: a placebo controlled trial
Authors: Erdtsieck R. J. , Pols H. A. P. , Valk N. K. , van Ouwerkerk B. M. , Lamberts S. W. J. , Mulder P. , Birkenhäger J. C. 
Published: March 2008

SummaryOBJECTIVE It is known that growth hormone can Induce accelerated bone turnover in GH deficient people as well as healthy elderly people. In this study we examined the effect of recombinant human GH (rhGH) on bone mineral mass and bone turnover in the presence of the bone resorption inhibiting agent, pamidronate. Effects on body composition were also studied.METHODS Twenty‐one post‐menopausal osteoporotic women were treated with the bisphosphonate pamidronate during 12 months. During the Initial 6 months rhGH (0.0675 IU/kg, 3 times/week) was administered In a placebo controlled fashion (10 vs 11 patients).MEASUREMENTS Bone mineral Content (BMC) of the lumbar spine and femoral neck was measured with dual‐energy X‐ray absorptiometry and BMC of the distal and proximal forearm with single‐photon absorptiometry. Body composition was measured with bioelectrical Impedance and total body dual‐energy X‐ray absorptiometry. Serum IGF‐I and biochemical indices of bone turnover were also measured.RESULTS The group treated with rhGH showed a two to three‐fold Increase In serum IGF‐I levels. No effects on bone mineral mass were observed in the group treated with rhGH, either after the Initial 6 months of treatment with rhGH or after the total period of 12 months. In women treated with pamidronate, however, a consistent increase of about 5% at the lumbar spine and somewhat less in the distal forearm was reached from 6 months onwards. In neither group was any change observed in BMC at the femoral neck or forearm.Compared to baseline, the biochemical measurements of bone turnover showed a decrease of about 50% in the pamidronate treated group, but this effect was blunted in the group additionally treated with rhGH.The body composition measurements showed clear effects of rhGH administration: a decrease in fat mass of about 5% and an increase In lean body mass of about 3%. However, these effects disappeared after the treatment with rhGH was stopped and both fat mass and lean body mass returned to Initial values.CONCLUSIONS The present study suggests that treatment with rhGH blunted both the pamidronate induced accumulation of bone mineral mass and the reduction of biochemical markers of bone turnover. Furthermore, the positive effect of rhGH on body composition disappears completely after cessation of treatment with rhGH.
Androgens and insulin resistance in type 1 diabetic men
Authors: Ebeling Pertti , Stenman Ulf‐Håkan , Seppälä Markku , Koivisto Veikko A. 
Published: March 2008

SummaryOBJECTIVE In healthy men, both high and low serum testosterone concentrations are associated with insulin resistance, whereas low concentration of sex hormone binding globulin (SHBG) is related to reduced insulin sensitivity. The aim of our study was to examine the association of sex hormones, SHBG, dehydroeplandrosterone (DHEAS) and insulin‐like growth factor binding protein‐1 (IGFBP‐1) on Insulin sensitivity in type 1 diabetic patients.PATIENTS We examined 23 male patients with the mean age of 29 ± 1 years, body mass index 22.9 ± 0.4 kg/m2, Insulin dose 47 ± 3 units/day, glycosylated haemoglobin (HbA1c) 7.8 ± 0.3% and duration of diabetes 13 ± 1 years.DESIGN Each patient was studied With a 4‐hour euglycaemic (5.5 ± 0.1 mmol/l), hyperinsulinaemic (612 ± 26 pmol/l) clamp with indirect calorimetry. Muscle biopsies (quadriceps femoris) for the determination of glycogen synthase were performed In 15 patients before and at the end of the clamp.RESULTS insulin infusion reduced the concentrations of IGFBP‐1 by 90% (P < 0.001), DHEAS by 11% (P < 0.001), and SHBG by 4% (P < 0.01), whereas free or bound testosterone levels remained unchanged. The fall in IGFBP‐1 level was closely related to the basal concentration (r= 099, P < 0.001). Basal SHBG concentration Correlated directly with total (r= 0.51, P <0.05) and non‐oxidative glucose disposal (r= 0.41, P < 0.05), and with the decrease in lipld oxidation (r= 0.47, P <0.05) during Insulin Infusion. The fall in SHBG was inversely related to the mean (30–240 min) FFA concentration durlng hyperinsulinaemia (r=‐0.64, P < 0.001). The fractional activity of glycogen synthase at the end of insulin infusion correlated directly with fasting SHBG (r= 0.71, P <0.01) and DHEAS concentrations (r= 0.67, P <0.01).CONCLUSIONS In male type 1 diabetic patients: (1) acute hyperinsulinaemia decreases IGFBP‐1, DHEAS and SHBG concentrations with the greatest decline in IGFBP‐1, (2) SHBG concentration is positively associated with factors Indicating good insulin sensitivity, (3) association between fuel homeostasis and SHBG, DHEAS and insulin antagonists suggests a network of these factors In the regulation of insulin action in type 1 diabetic patients.
Hexarelin induced growth hormone release is influenced by exogenous growth hormone
Authors: Massoud Ahmed F. , Hindmarsh Peter C. , Brook Charles G. D. 
Published: March 2008

SummaryOBJECTIVE Growth hormone releasing peptides (GHRPs) are a group of synthetic compounds capable of releasing GH by an unknown mechanism. The aim of this study was to determine the effect of administering biosynthetic human growth hormone (rhGH) on the GH releasing activity of hexarelin, a new and potent GHRP, and to compare the results with those obtained with growth hormone releasing hormone (GHRH).DESIGN Boluses of saline or rhGH were administered intravenously, followed 90 minutes later by a second intravenous bolus of saline, hexarelin or GHRH. Studies were performed following an overnight fast. Each subject underwent six studies performed in a random order and separated by at least 2 days.SUBJECTS Six healthy adult males (23.8–34.3 years) were studied.MEASUREMENTS Serum GH and IGF‐I levels were measured by radioimmunoassay.RESULTS The peak serum GH response to hexarelln was greater than that to GHRH, irrespective of whether the first bolus was saline (P < 0.05) or rhGH (P < 0.02). Prior administration of rhGH led to a reduction in peak serum GH response to hexarelin or GHRH (P < 0.05); the percentage reduction in response to hexarelin was less than that to GHRH, but this difference was not statistically significant (P= 0.3). There was no change In serum IGF‐l concentration before or 90 minutes after the administration of rhGH.CONCLUSIONS Hexarelin is a potent GH secretagogue subject to partial feedback Inhibition by rhGH. This raises issues about its mechanism of action and may have implications for its potential therapeutic use.
Intranasal administration of the GHRP hexarelin accelerates growth in short children
Authors: Laron Z. , Frenkel J. , Deghenghl R. , Anin S. , Klinger B. , Siibergeld A. 
Published: March 2008

SummaryOBJECTIVE Hexarelin is a recently synthesized small growth hormone releasing peptide (GHRP) (His‐D‐methyl‐Trp‐Ala‐Trp‐D‐Phe‐Lys‐NH2). It Is actlve by intra‐venous, oral and intranasal administration In animals and man. The aim of this study was to find out whether longterm administration of this peptlde would promote growth In short chlldren.DESIGN AND PATIENTS intranasal hexareiin was administered in a dose of 60 pglkg thrice dally to 8 prepubertal short children aged 4‐11‐6 years for perlods of up to months.RESULTS Hexarelln treatment stimulated Insulin‐like growth factor‐i (IGF‐I) secretion ralsing the level from 10.4 ± 3.9 (SD) to 141 f 46 nmoill (P < 0.004). The rise IGF‐l led to a significant Increase In the mean (±SD) linear growth velocity from 53 ± 08 to 8 3 ± 1.7 cm/year (P < 0.0001). There was also a slgniflcant decrease skinfold thickness despite Increase in body weight and an Increase in head circumference. Additional flndlngs were a rlse in serum phosphate from 1–5 ± 01 to 1–8 ± 01 mmoi/l (P < 0004) and of aikallne phosphatase from 219 ± 74 to 261 ± 75 U/l (P < 005).CONCLUSIONS The long‐term GHIIGF‐I stimulating, anabolic and growth promoting effects achieved by intranasai administration of this hexapeptide, seemingly without undeslrable slde‐effects, suggests clinical potential for this new class of drugs.
Natural selection on and predicted responses of ecophysiological traits of swamp milkweed (Asclepias incarnata)
Authors: Agrawal Anurag A. , Erwin Alexis C. , Cook Susan C. 
Published: March 2008

Summary

Given the rapid and reversible impact of the environment on plant ecophysiological traits, it has been speculated that such traits may have low heritabilities, high phenotypic plasticity and experience selection which is highly variable.
We estimated heritabilities, phenotypic plasticity and natural selection on five ecophysiological traits (carbon : nitrogen (C : N) ratio, leaf water content, specific leaf area (SLA), trichome density and water use efficiency (WUE)) of swamp milkweed Asclepias incarnata. In a 2‐year field experiment, we studied 49 full‐sibling families in a common garden and assessed phenotypic and genotypic selection.
Consistent evidence indicated selection for increased leaf trichome density and reduced WUE. Less strong evidence suggested selection for reduced SLA and leaf water content, and there was no selection on C : N of leaves.
Although the ecophysiological traits showed many phenotypic and genetic correlations, we found little evidence that these correlations would constrain adaptive evolution.
To evaluate the phenotypic plasticity of the same traits, we conducted a separate growth chamber experiment and found evidence that leaf water content, SLA and C : N responded to environmental conditions (herbivory, water stress, nutrient addition).
Synthesis. We have demonstrated natural selection on ecophysiological traits and their probable response to selection with a genotypic selection analysis. We cautiously reject the notion that these traits lack heritable variation and that genetic correlations among them constrain their response to selection. Thus, plants such as A. incarnata appear capable of adaptive responses in their ecophysiological traits.
Induction of Experimental Arthritis in Balb/C Mice by Inclusion of a Foreign Protein in the Collagen Inoculum
Authors: Bäckström N. F. , Dahlgren U. I. H. 
Published: March 2008

AbstractThe susceptibility of mice to collagen‐induced arthritis (CIA) has, among other things, been linked to the major histocompatibility complex class II genes as well as other genes. This study was designed to examine the possibilities to establish CIA in low susceptible I‐Ad (Balb/C) mice. Balb/C mice were immunized twice with bovine type II collagen (BCII) in complete Freund’s adjuvant (CFA) containing the amount of Mycobacterium tuberculosis needed to induce CIA in low susceptible I‐Ab (C57BL/6) mice. Some mice received the conceivable arthritogenic inoculum mixed with ovalbumin (OVA). Clinical arthritis was monitored. Antibody activity and T‐cell reactivity to BCII were determined. Unexpectedly, only mice that were immunized with the BCII–OVA mixture developed arthritis. Combining BCII with another foreign protein, keyhole limpet hemocyanin, but not the self‐protein mouse serum albumin, also triggered arthritis. Prior to the appearance of arthritis the serum levels of IgG autoantibodies to BCII were higher in the coimmunized mice than in the mice that were immunized with BCII alone. Yet, splenocytes stimulated in vitro with BCII did not proliferate or produce interferon‐γ. Immunization of Balb/c mice with an emulsion‐containing CFA and BCII mixed with a foreign body, but not a self‐protein, elevates the level of circulating autoantibodies to CII and subsequently induces arthritis.
REPETITIVE SHARP WAVE ON THE ELECTROENCEPHALOGRAM—Report of 2 Cases With Both Cerebral Disease And Hepatic Dysfunction—
Authors: Miyazaki Motoji , Ebe Mitsuru , Aki Motoo 
Published: March 2008

SummaryTwo cases were reported in which the repetitive sharp waves consisted of main electroencephalographic feature. In contrast to the previous reports of this particular discharge which were noted in subacute progressive encephalitis, subacute vascular encephalopathy, cerebral lipidosis, hepatic coma and hyperammonemia, pathological diagnoses of our two cases were acute disseminated encephalomyelitis and cerebral metastases of pulmonary adenocarcinoma and in addition hepatic dysfunction in both cases. Owing to the diversity of the disaass showing similar REG feature, we are inclined to believe the non‐specificity of the pattern. Alteration of the pattern in concordance with the progress of the disease makes us favor a biochemical affair as an inducing mechanism rather than structural damage of specific areas concerned.
HISTOCHEMICAL STUDY ON HEPATOLENTICULAR DEGENERATION
Authors: Arioka Iwao , Tanimukai Hiroshi , Nishimura Tsuyoshi , Nishinuma Keiji , Ueda Masaharu 
Published: March 2008

SummaryThe brain and liver of five classical cases of hepatolenticular degeneration were histochemically examined for copper and iron. Within the brain, both copper and iron were detected in two cases. Coppsr was demonstrated in the liver of all cases and iron in two cases. The histochemical findings obtained were discussed.
CORTICAL AND RETICULAR EFFECTS UPON EVOKED ACTIVITY OF THALAMIC SOMATOSENSORY RELAY NUCLEUS
Authors: Iwama Kitsuya , Yamamoto Chosaburo 
Published: March 2008

SummaryUsing cats and dogs, effects of cortical and reticular formation stimulation were examined upon the thalamic evoked potential produced by single shock stimulation of the posterior funiculus. Cortical stimulation was done with a single shock applied to the sensorimotor cortex of one side ipsilateral to the thalamic somatosensory relay nucleus which is to be activated by posterior fimiculus stimulation. The reticular formation was stimulated at the mesencephalic level repetitively with shocks of varying frequencies for about 0.1 second.1. Cortical stimulation, when made 100–200 msec prior to posterior funiculus stimulation, was followed by an augmentation of the delayed component of the thalamic evoked potential and a suppression of the initial one.2. The thalamic evoked potential suffered suppression by repetitive stimulation of the reticular formation. Among the initial and delayed components of the thalamic evoked potential, the former was more resistant to the reticular suppression than the latter. The suppression was most marked immediately after the end of reticular stimulation.3. A small dose of barbiturate, injected intravenously, abolished the suppressing effect of reticular origin with the cortical effect well preserved.4. An extensive lesion of the reticular core at the intercollicular level facilitated the delayed component of the thalamic evoked potential. Even under this condition the cortical facilitatory action could be elicited.
AN ELECTRON MICROSCOPIC STUDY ON CEREBRAL SWELLING, ESPECIALLY ON THE CHANGES IN THE NERVE CELLS
Authors: Sekiya Toru 
Published: March 2008

SummaryThe nerve cells in the brain stem of animals suffering from cerebral swelling produced by liver injuries and in the cerebral cortex of a human with the increase of brain volume associated with a metastatic intracerebral hypernephroma were comparatively investigated in the electron‐microscopic preparations.1. In experimental cerebral swelling, morphological changes were observed in the nerve cells. These changes were classified into “vacuolar changes” and “shrinking changes” on the basis of electron‐microscopic findings.1) The “swelling changes” did not bring on any remarkable changes in the nucleus but were characterized by vacuolated mitochondria and lessened density of the cytoplasmic ground substances. The so‐called vacuolar appearance as described light‐microscopically might be based upon the decreased quantity of Palade's particles and very marked swelling of mitochondria in the cytoplasm.2) Shrinked nucleus and dense appearance of the cytoplasmic ground substances were the characteristics of the “shrinking changes”; It seems that the so‐called cell shrinkage light‐microscopically is due to the shrinkage of nuclei and the dense package of Palade's particles in the cytoplasm.2. Perineuronal satellite glial cells could be found even in ultra‐thin sectioned samples. Especially, in cerebral swelling more than two satellites were often observed. The electron micrographs showing the cytoplasmic fusion between a nerve cell and the glial cells might be considered to correspond to the so‐called pseudoneuronophagia because of the “shrinking changes” observed in the nerve cell, although the identity of such figures is uncertain in terms of classical neuro‐pathology.3. Since the “vacuolar changes”, analogous to those observed in cases of experimentally produced cerebral swelling, including the characteristic of the vacuolation of mitochondria, were found in the nerve cells in the case of human brain with the metastatic hypernephioma, it is highly probable that this human brain falls under the category of cerebral swelling.It was found, thus, that the changes in electron micrographs of nerve cells in cerebral swelling experimentally produced mainly by hepatic injuries were analogous to those of the nerve cells in the increase in volume of the human brain produced by the metastatic hypernephroma without any liver diseases. This finding may become an important key for the clarified phenomena in cerebral swelling caused by various factors.
EFFECT OF RETICULAR AND HYPOTHALAMIC STIMULATION UPON THE SUSCEPTIBILITY OF THE NEOCORTEX, AMYGDALA AND HIPPOCAMPUS TO SEIZURE DISCHARGES
Authors: Miyasaka Matué , Kawamura Hiroshi 
Published: March 2008

SummaryThe effects of high frequency electrical stimulation of the mid‐brain reticular formation and the hypothalamus upon the susceptibility of the neocortex, amygdala and hippocampus to the locally induced seizure discharge were studied in 25 non‐anesthetized, curarized cats.1) Facilitatory effect on the neocortical seizure discharge: The preceding stimulation of the mid‐brain reticular formation and posterior hypothalamus which provoked markedly the desynchronized arousal pattern of the neocortex lowered the threshold or prolonged the duration of neocortical seizure discharge.2) Inhibitory effect on the seizure discharges of the amygdala and hippocampus:The preceding stimulations of the hypothalamus and mid‐brain reticular formation, which provoked the typical arousal patterns of the amygdala or hippocampus, elevated the threshold or shortened the duration of the seizure discharges of the amygdala or hippocampus.3) Opposite effects between the stimulations of the anterior part and posterior part of the hypothalamus upon the hippocampal seizure discharge: The preceding stimulations of the posterior hypothalamus and mid‐brain reticular formation, which provoked the regular slow activity in the hippocampus, elevated the threshold or shortened the duration of hippocampal seizure discharge. On the other hand, the preceding stimulation of the anterior part of the hypothalamus, which provoked low voltage fast activity in the hippocampus, lowered the threshold or exceedingly prolonged the duration of hippocampal seizure discharge.The above remarked experimental results were discussed in relation to the clinical and electroencephalographid knowledges of the psychomotor and the other types of epilepsy.