bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenal Splanchnic Innervation Modulates Adrenal Cortical Responses to Dehydration Stress in Rats
Authors: Ulrich-Lai Yvonne M. , Engeland William C.
Published: April 2003

Classically, the production of glucocorticoids by the adrenal gland is thought to be controlled exclusively by adrenocorticotropic hormone (ACTH). However, there are several examples in stressed humans and animals of increased plasma glucocorticoids in the absence of increased plasma ACTH, suggesting that an additional, non-ACTH mechanism(s) may contribute to the control of glucocorticoid production. The present studies were designed to determine the role of the thoracic splanchnic nerve in controlling plasma corticosterone levels in response to chronic water deprivation in rats, a model previously reported to demonstrate dissociations between plasma corticosterone and ACTH. Briefly, rats underwent right unilateral adrenalectomy and left thoracic splanchnic nerve transection or sham transection. After recovery, rats were water deprived for 48 h or given free access to water, and then sacrificed for collection of plasma and adrenal glands. Water deprivation resulted in consistent, robust increases in plasma corticosterone that were attenuated by splanchnic nerve transection, in the absence of changes in post-dehydration plasma ACTH. Adrenal content of steroidogenic acute regulatory factor (StAR) and cyclic AMP (cAMP) were increased after dehydration; splanchnic nerve transection decreased post-dehydration adrenal cAMP, but not StAR. Splanchnic nerve transection also attenuated plasma corticosterone responses to submaximal doses of ACTH in dexamethasone-blocked, dehydrated rats, suggesting a decreased adrenal sensitivity to ACTH. Collectively, the present results demonstrate that the thoracic splanchnic nerve normally augments the adrenal corticosterone response to dehydration stress by increasing adrenal sensitivity to ACTH, and this augmentation is associated with elevations in adrenal cAMP content. These data support the hypothesis that the splanchnic innervation of the adrenal gland represents an additional physiological mechanism to control stress-induced adrenal cortical responses in vivo.
Prolactin-Releasing Peptide Releases Corticotropin-Releasing Hormone and Increases Plasma Adrenocorticotropin via the Paraventricular Nucleus of the Hypothalamus
Authors: Seal Leighton J. , Small Caroline J. , Dhillo Waljit S. , Kennedy Adam R. , Ghatei Mohammad A. , Bloom Stephen R.
Published: April 2003

Intracerebroventricular (ICV) injection of prolactin-releasing peptide (PrRP) is known to increase plasma adrenocorticotropin (ACTH) and cause c-fos expression in the hypothalamic paraventricular nucleus (PVN). We hypothesize that this is the site at which PrRP acts to increase plasma ACTH. We have used ICV injection and direct intranuclear injection of PrRP into the PVN to investigate the sites important in the stimulation of ACTH release in vivo. To investigate the mechanism of action by which PrRP increases ACTH, we have used primary culture of pituitary cells and measured neuropeptide release from in vitro hypothalamic incubations. ICV administration of PrRP increased plasma ACTH 10 min post-injection (PrRP 5 nmol 81.0 ± 23.5 pg/ml vs. saline 16.8 ± 14.1 pg/ml, p < 0.05). Intra-PVN injection of PrRP increased ACTH 5 min post-injection (PrRP 1 nmol 22.9 ± 5.0 pg/ml vs. saline 10.3 ± 1.4 pg/ml, p < 0.05). This effect continued until 40 min post-injection (PrRP 1 nmol 9.9 ± 1.5 pg/ml vs. saline 6.2 ± 0.5 pg/ml, p < 0.05). In vitro PrRP (1–100 nmol/l) did not effect basal or corticotropin-releasing hormone (CRH)-stimulated ACTH release from dispersed anterior pituitary cells. PrRP increased hypothalamic release of CRH (PrRP 100 nmol/l 1.4 ± 0.2 nmol/explant vs. the basal 1.1 ± 0.2 nmol/explant, p < 0.05) but not arginine vasopressin. PrRP also stimulated neuropeptide Y release (PrRP 100 nmol/l 56.5 ± 11.8 pmol/explant vs. basal 24.0 ± 1.9 pmol/explant, p < 0.01), a neuropeptide known to stimulate the hypothalamo-pituitary-adrenal axis. Our data suggest that in vitro PrRP does not have a direct action on the corticotrope but increases plasma ACTH via the PVN and this effect involves the release of hypothalamic neuropeptides including CRH and neuropeptide Y.
The Amygdala Regulates the Pituitary-Adrenocortical Response and Release of Hypothalamic Serotonin following Electrical Stimulation of the Dorsal Raphe Nucleus in the Rat
Authors: Weidenfeld Joseph , Newman Michael E. , Itzik Anna , Gur Eitan , Feldman Shaul
Published: April 2003

The amygdala is known to modulate the function of the hypothalamo-pituitary-adrenocortical (HPA) axis, but the mechanism of this effect is still not clear. In the present study we examined the specific role of the serotonin (5-HT) system in mediating the effect of the amygdala on the activity of the HPA axis. Bilateral lesions of the amygdala in rats reduced the adrenocorticotropin (ACTH) and corticosterone responses to electrical stimulation of the dorsal raphe nucleus, where the cell bodies of serotonergic neurons are located. Amygdala lesions had no effect on the ACTH and corticosterone responses to administration of a 5-HT1A receptor agonist directly into the paraventricular nucleus (PVN) of the hypothalamus, indicating that there was no impairment in the activity of postsynaptic 5-HT1A receptors in the hypothalamus. In vivo microdialysis showed that amygdala lesions markedly attenuated the effect of electrical stimulation of the dorsal raphe to increase extracellular secretion of 5-HT in the PVN. This is the first demonstration that the amygdala has a facilitatory effect on the function of dorsal raphe 5-HT neurons which project to the PVN, and suggests a mechanism by which the amygdala may modulate the function of the HPA axis.
Recovery from Hemodialysis Therapy in a Patient with Renal Cholesterol Crystal Embolism
Authors: Kato Akihiko , Ohtsuji Akiko , Terada Tatsuhiro , Goto Tetsuo , Fukasawa Hirotaka , Yasuda Hideo , Togawa Akashi , Fujimoto Taiki , Suzuki Hiroyuki , Fujigaki Yoshihide , Yamamoto Tatsuo , Yonemura Katsuhiko , Hishida Akira
Published: April 2003

The prognosis of renal cholesterol crystal embolism (CCE) is poor, and many patients progressively develop to the end-stage of chronic renal failure. We herein experienced a 66-year-old male patient who recovered from hemodialysis (HD) shortly after an amputation of inflammatory toes. The patient complained of painful digital cyanosis at bilateral toes and livedo reticularis at right lower leg 4 weeks following aortic angiography. Laboratory examinations revealed eosinophilia and overt proteinuria (3.0 g/day). His serum creatinine level increased from 2.18 to 8.57 mg/dl over 6 weeks, and HD treatment was started. Treatment with simvastatin (5 mg/day) did not reverse renal failure and hypereosinophilia, but the amputation of right gangrene toes promptly increased urine output and eosinophilia completely disappeared concomitantly with a decline of C-reactive protein from 9.7 to 0.7 mg/dl. Serum creatinine level was also reduced to 3.46 mg/dl, and he eventually stopped HD totally after 32 sessions. This case suggested that the surgical amputation promptly recovered renal function. Reversal of inflammation may be more effective than lipid-lowering therapy for renal failure in our patient.
Increased Expression of Glomerular Mesangial Cell 5’-Nucleotidase in Membranous Nephropathy
Authors: Savić Vojin , Vlahović Predrag , Stefanović Vladisav
Published: April 2003

It has been demonstrated in anti-Thy1 glomerulonephritis that extracellular adenine nucleotides have a significant pro-inflammatory activity, however, glomerular ATP/ADPase, which in concert with 5′-nucleotidase converts ATP/ADP, and AMP to anti-inflammatory adenosine had an anti-inflammatory role. We have studied distribution of 5′-nucleotidase and divalent cation-activated ATPase in kidney biopsies of 15 patients with glomerulonephritis. The major finding was an overexpression of 5′-nucleotidase in the mesangium of kidney from patients with membranous nephropathy. No change in 5′-nucleotidase expression was observed in other common forms of glomerulonephritis: IgA nephropathy, mesangioproliferative and mesangiocapillary glomerulonephritis. The distribution of Mg2+-ATPase in investigated specimens was similar to control distribution. Results obtained in this study indicate increased mesangial expression of 5′-nucleotidase in non-proliferative form of glomerulonephritis consistent to a role of mesangial cells in inflammatory processes.
Effect of Polyamines on Mesangial Cell Ecto-5′-Nucleotidase and Ecto-ATPase Activity
Authors: Stefanović Vladisav , Mitić-Zlatković Marina , Savić Vojin , Vlahović Predrag
Published: April 2003

Polyamines were found to modulate the activity of several membrane-bound enzymes, participating in cell growth and differentiation. We have studied the effect of polyamines (spermidine, spermine and putrescine) on rat mesangial cell ectoenzymes: 5′-nucleotidase, Mg2+-ATPase and Ca2+-ATPase. Ecto-5′-nucleotidase activity was significantly increased after 48 h treatment with spermine and spermidine. Mg2+-ATPase was increased only after treatment with spermidine; however, Ca2+-ATPase was significantly increased after both spermine and spermidine treatment of mesangial cells. Culture of mesangial cells with putrescine did not change the activity of these ectoenzymes. Increased expression of mesangial cell ecto-ATPase and ecto-5′-nucleotidase after spermine and spermidine treatment could result in an increased production of adenosine, a powerful autacoid interesting with respect to a role of mesangial cells in inflammatory processes.
A Comparison between the Soluble Transferrin Receptor, Transferrin Saturation and Serum Ferritin as Markers of Iron State in Hemodialysis Patients
Authors: Beerenhout Charles , Bekers Otto , Kooman Jeroen P. , van der Sande Frank M. , Leunissen Karel M.L.
Published: April 2003

An adequate iron management is important in the treatment of anemia and in hemodialysis (HD) patients. Serum ferritin and transferrin saturation (TS) may be influenced by the presence of inflammation. Recently, the soluble transferrin receptor (s-TfR) has been advocated as a parameter of iron status in HD patients. The aim of the present study was to assess firstly the relation between serum ferritin, TS, and s-TfR in HD patients and to predict their agreement (assessed by kappa) in the diagnosis of iron deficiency, and, secondly, to assess the influence of inflammation on the relation between the parameters of iron state. Iron deficiency by either marker was respectively defined as ferritin <100 µg/l, TS <20%, or s-TfR >2.4 µg/ml. In the overall group of patients, TS and s-TfR were significantly related (r = –0.38), whereas s-TfR and serum ferritin were not. Both serum ferritin and TS were related to CRP (r = 0.50 and –0.34; p < 0.05), whereas s-TfR was not. The kappa value for agreement between serum ferritin and TS in the diagnosis of iron deficiency was 0.24 (p = 0.07), 0.12 (p = NS) for the agreement between TS and s-TfR and 0 for that between serum ferritin and s-TfR. In patients with CRP levels ≤2 mg/l (n = 16), the relation between parameters of iron state did not improve. Concluding, a large disagreement is observed between ferritin, TS and sTfR as markers of iron deficiency in HD patients, which appears to be only partly explained by the effect of inflammation.
Adjusting Dry Weight by Extracellular Volume and Body Composition in Hemodialysis Patients
Authors: Chen Yi-Chou , Chen Han-Hsiang , Yeh Jui-Chi , Chen Ssu-Yuan
Published: April 2003

Background: At present, the determination of dry weight in patients on hemodialysis is largely made empirically by trial and error. Extracellular volume (ECV) assessment by bioimpedance analysis (BIA) is a preferable technique for determining dry weight, and it also provides useful data on body composition. Methods: We measured the ECV of 74 normal subjects and 121 stable chronic hemodialysis patients postdialysis. In addition, for the dialysis patients, we measured intracellular volume (ICV) and lean body mass (LBM) by BIA, and analyzed the ECV, blood pressure and complications of dialysis. We adjusted dry weight according to the ECV and repeated a BIA exam 4 months later to evaluate changes in body composition, blood pressure and dialysis status of these patients. Results: The ECV as a percentage of weight (ECV%) of hypertensive patients was significantly higher than that of normotensive patients (24.29 ± 3.56% vs. 21.50 ± 2.38%, p < 0.001). All patients with excessive ECV% had hypertension, but not all hypertensive patients had excessive ECV%. None of the normotensive patients had ECV excess. Some hypertensive patients with symptoms of dialysis complications still had excessive ECV%. Eight hypertensive patients with excessive ECV had decreased dry weight. ECV% (29.80 ± 2.03% vs. 27.10 ± 2.99%, p < 0.001) and blood pressure (159 ± 7 / 97 ± 4 vs. 137 ± 10 / 86 ± 8 mm Hg, p = 0.006 for systolic and p = 0.004 for diastolic) decreased. ECV was the only portion of body composition that decreased (p < 0.001) after decreasing dry weight, the other parameters remaining unchanged. Twenty symptomatic normotensive patients improved with elevation of the dry weight. The ECV (p = 0.007), ICV (p = 0.009) and LBM (p < 0.001) were significantly increased after increasing dry weight, while the ECV% (p = 0.39) and fat (p = 0.46) remained unchanged. Conclusions: (1) For hypertensive patients, ECV must be evaluated in order to adjust dry weight and correct hypertension. (2) For normotensive patients, if dialysis complications occur, dry weight should be increased until symptoms disappear or the blood pressure begins to rise.
Usage of T Cell Receptor Variable Segments of the Beta-Chain in IgA Nephropathy
Authors: Muro Kaori , Yamagata Kunihiro , Kobayashi Masaki , Hirayama Kouichi , Koyama Akio
Published: April 2003

Background: We previously reported that glomerulonephritis associated with Staphylococcus aureus infection (SAGN) showed an increased usage of T cell receptor Vβ 5.3 and 8 in peripheral lymphocytes and mesangial IgA and IgG depositions. To elucidate the immunological mechanisms and pathogenesis of IgA nephropathy, we analyzed the usage of TCR Vβ in both peripheral blood lymphocytes (PBLs) and renal infiltrating T cells from IgA-N patients. Methods: In 38 patients with IgA nephropathy and controls, the usage of TCR Vβ in PBLs were analyzed using monoclonal antibodies against Vβ 3.1, Vβ 5.1, Vβ 5.2 + 5.3, Vβ 5.3, Vβ 6.7, Vβ 8, Vβ 12.1, and Vβ 13.1 + 13.3 with three-color flow cytometry. Furthermore, we examined immunohistochemically renal biopsy specimens using antibodies against Vβ 5.3 and Vβ 8. Results: The percentages of DR+CD4+CD8– cells, CD45RO+CD4+ cells, and CD45RO+CD4+DR+ cells in PBLs from IgA nephropathy were significantly higher than controls. The percentages of TCR Vβ 5.3 positive cells and TCR Vβ 8 positive cells in PBLs from patients were 1.3 ± 0.1 and 3.1 ± 0.2%, and both were significantly higher than controls. The percentage of renal interstitial TCR Vβ 5.3 expression was significantly higher than that in PBLs. However, there was no significant difference between the TCR Vβ 8 expression in the interstitium and that in PBLs. Conclusions: TCR Vβ 5.3 and 8 usage and broad CD4+ T cell activation have occurred in IgA nephropathy. These changes were similar but weak compared with formerly reported SAGN.
Adult Height in Congenital Hypothyroidism: Prognostic Factors and the Importance of Compliance with Treatment
Authors: Bain Philippa , Toublanc Jean-Edmond
Published: April 2003

Objective: To study the growth, puberty and compliance of 66 hypothyroid children and to determine prognostic factors for adult height. Patients: 66 children were included (12 boys, 54 girls). Aetiologies were 43 ectopic glands, 14 thyroid agenesis, 9 dyshormonogenesis. Results: In girls the mean adult height was 164.7 ± 6.5 cm for a target height (TH) of 162.8 ± 5.4 cm. In boys the mean adult height was 178.2 ± 6.4 cm for a TH of 175.7 ± 4.7 cm. Puberty development was normal. Children who exceeded their TH had an earlier start of treatment versus children who failed to reach their TH: 24.8 ± 13.5 vs. 42.0 ± 47.3 days, p = 0.004. Delayed normalisation of TSH is a risk factor for bad compliance. Adequate correlations between treatment variables appeared only in children who exceeded their TH. Conclusions: TH, day of start of treatment and compliance with treatment are the main prognostic factors for adult height. Early detection of bad compliance is possible.
Evaluation of High-Dose Estrogen and High-Dose Estrogen plus Methyltestosterone Treatment on Cognitive Task Performance in Postmenopausal Women
Authors: Wisniewski Amy B. , Nguyen Tam T. , Dobs Adrian S.
Published: April 2003

Objectives: To investigate the cognitive effects of high-dose oral estrogen alone or in combination with oral methyltestosterone in postmenopausal women. Methods: Participants were tested with a randomized, double-blind design on the Identical Pictures, Cube Comparisons, Building Memory and Shape Memory tasks before and after 4 months of hormone treatment. Results: Women receiving estrogen and methyltestosterone maintained a steady level of performance on the Building Memory task, whereas those receiving estrogen alone showed a decrease in performance. Conclusions: These results indicate that the addition of testosterone to high-dose estrogen replacement exerts a protective effect on memory performance in postmenopausal women.
An Autocrine Role for Pituitary GABA: Activation of GABA-B Receptors and Regulation of Growth Hormone Levels
Authors: Gamel-Didelon Katia , Corsi Claudia , Pepeu Giancarlo , Jung Heike , Gratzl Manfred , Mayerhofer Artur
Published: April 2003

There is increasing evidence suggesting that the neurotransmitter γ-aminobutyric acid (GABA) is a local factor involved in the regulation of endocrine organs. Examples of such functions are documented in the pancreas, but recent results suggest that GABA may act in a similar way in the pituitary, in which GABA receptors are expressed and pituitary growth hormone (GH) cells provide a source of GABA. We hypothesised that GABA secreted in somatotropes may act as an autoregulatory signaling molecule. To test this hypothesis we first examined the nature of GABA receptors expressed by GH cells. RT-PCR analysis demonstrated that GABA-B receptor subunits R1 and R2 are present in the whole rat pituitary. Laser microdissection of immunostained GH cells, followed by RT-PCR as well as immunoelectron microscopy, showed that GABA-B receptors are expressed on somatotropes. To investigate GABA-B receptor function in somatotropes, we used rat GH3 adenoma cells, which, like pituitary GH cells, express GABA-B R1 and R2 (as assessed by RT-PCR and immunoelectron microscopy) and produce GABA (checked by high performance liquid chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a chromatography). After inhibition of endogenous GABA synthesis, GH production was stimulated by baclofen, a GABA-B receptor agonist. By contrast, blocking GABA-B receptors by an antagonist, phaclofen, decreased GH levels. We conclude that in GH-producing cells, GABA acts as an autocrine factor via GABA-B receptors to control GH levels.
Splenic Denervation Blocks Leptin-Induced Enhancement of Humoral Immunity in Siberian Hamsters (Phodopus sungorus)
Authors: Demas Gregory E.
Published: April 2003

Nontropical rodents have evolved adaptations to maximize winter survival, including alterations in reproduction, energy balance and immunity. Short-day-housed Siberian hamsters display reductions in body fat and decreases in humoral immunity compared with long-day hamsters. The hormone leptin, secreted by adipose tissue, varies in response to changes in body fat and has been implicated in photoperiodic changes in immunity. In addition, the metabolic effects of this hormone appear to be mediated by the sympathetic nervous system (SNS). Very little is known, however, regarding the role of the SNS in regulating the effects of leptin on immunity. The goal of the present study was to examine the effects of splenic denervation on leptin-induced immune enhancement of short-day Siberian hamsters. Male hamsters were housed in long (LD 16:8) or short days (LD 8:16) for 10 weeks. Half of the animals in each photoperiod received surgical denervations of the spleen; the remaining animals received sham operations. In addition, animals in each group were implanted with osmotic minipumps containing either leptin or vehicle. Hamsters were then injected with keyhole limpet hemocyanin (KLH) and serum anti-KLH antibody production was assessed. Short-day hamsters displayed decreased humoral immunity in short versus long days; leptin attenuated the short-day decrease but did not enhance immunity of long-day hamsters. Furthermore, splenic denervation blocked the leptin-induced increase in immunity in short-day hamsters. Collectively, these data suggest that leptin plays an important role in regulating seasonal changes in humoral immunity of Siberian hamsters and the effects of leptin occur, at least in part, via changes in the SNS innervation of lymphoid tissue.
UVB-Irradiated Dendritic Cells Induce Nonproliferating, Regulatory Type T Cells
Authors: Simon J.C. , Hara H. , Denfeld R.W. , Martin S.
Published: April 2003

It is well established that low-dose UVB radiation inhibits the antigen-presenting cell (APC) function of murine Langerhans cells in vivo and converts them from immunogenic to tolerogenic APC. Recently, we have shown that UVB-irradiated murine bone marrow-derived dendritic cells (UVB-DC) suppressed proliferation of naive and primed T cells, but tolerized primed T cells only. To examine the underlying mechanism for these differences, naive OVA323–339-peptide-specific, TCR-transgenic T cells from DO11.10 mice were analyzed following coculture with unirradiated DC or UVB-DC. First, we found that UVB-DC inhibit OVA-specific T cell proliferation UVB dose and antigen dose dependently. Analysis of T cells cocultured with both, unirradiated and UVB-DC, revealed an activated T cell phenotype with increased expression of CD25 and CD69 by FACS. Supernatants harvested from cocultures with UVB-DC showed reduced levels of IFN-γ, IL-2 and IL-4, but not TGF-β, compared with unirradiated DC as determined by ELISA. Furthermore, these T cells did not proliferate upon restimulation. Interestingly, addition of these nonproliferating T cells to cocultures of naive T cells and freshly prepared unirradiated DC inhibited T cell proliferation depending on the number of added nonproliferating T cells. Also, in supernatants, increased levels of TGF-β were found. Therefore, our data indicate that UVB-DC propagate T cells with a regulatory function. Since regulatory T cells are characterized by enhanced TGF-β secretion and increased CTLA-4 expression, we currently investigate the role of CTLA-4 phenotypically and functionally. In conclusion, we have shown that UVB-DC inhibit proliferation of naive OVA-specific T cells. These T cells, exhibiting an activated phenotype and increased TGF-β production, suppress proliferation of naive T cells cocultured with unirradiated DC. These results suggest that UVB-DC induce nonproliferating, regulatory type T cells.
Melatonin Suppresses Reactive Oxygen Species in UV-Irradiated Leukocytes More than Vitamin C and Trolox
Authors: Fischer Tobias W. , Scholz Georg , Knöll Brunhilde , Hipler Uta-Christina , Elsner Peter
Published: April 2003

To prove the relative potency of melatonin as a radical scavenger in UV-irradiated leukocytes, it was compared to other antioxidative substances such as trolox and vitamin C. Human leukocytes were isolated from EDTA whole blood and incubated with melatonin, trolox and vitamin C. The experiments were performed in a wide concentration range from 0.1 nM to 1 mM and in a small concentration range from 0.5 to 2 mM (mel), 5 mM (trolox) and 10 mM (vit. C). Irradiation was performed with UV-light (280-360 nm) at a dose of 750 mJ/cm2. Radical formation was measured by the chemiluminescence technique. The maximum effect of radical suppression was seen at a concentration of 10 nM (p = 0.003) and 1 mM melatonin (p < 0.001) and vitamin C (p = 0.002; p < 0.001), respectively. ROS suppression by trolox was only significant at 1 mM (p < 0.001). In the small concentration range, a linear dose-response relationship was found and melatonin showed the strongest radical suppression (IC50 = 0.21 mM) followed by vitamin C (IC50 = 0.26 mM) and trolox (IC50 = 1.03 mM).
Emblica Cascading Antioxidant: A Novel Natural Skin Care Ingredient
Authors: Chaudhuri Ratan K.
Published: April 2003

A standardized extract of Phyllanthus emblica (trade named Emblica) was found to have a long-lasting and broad-spectrum antioxidant activity. The product has no pro-oxidation activity induced by iron and/or copper because of its iron and copper chelating ability. Emblica helps protect the skin from the damaging effects of free radicals, non-radicals and transition metal-induced oxidative stress. Emblica is suitable for use in anti-aging, sunscreen and general purpose skin care products.
Interventional Neurophysiological Mapping during Spinal Cord Procedures
Authors: Deletis V. , Bueno De Camargo A.
Published: April 2003

As part of interventional neurophysiology’s growing armamentarium, we present two intraoperative mapping techniques that can be used to guide the neurosurgeon during spinal cord procedures. They are: (1) Dorsal Column Mapping (DCM) and (2) Mapping of the Corticospinal Tract (CT) within the spinal cord. These two techniques are currently in different stages of development and clinical trials.
Spiegel and Wycis – The Early Years
Authors: Gildenberg Philip L.
Published: April 2003

The field of human stereotactic surgery was introduced by Ernest A. Spiegel and Henry T. Wycis by a historical paper in Science in 1947. Spiegel was a conservative Vienna trained experimental neurologist who fled the Nazis to Temple Medical School in Philadelphia. Wycis was a huge flamboyant but brilliant neurosurgeon who started as Spiegel’s student and then became his collaborator. They described a Horsley-Clarke apparatus that could be used in human stereotactic surgery. It relied on internal cerebral landmarks, which made it accurate enough to be used in humans. The fields of human neurophysiology, pneumoencephalography, radiology, and electrophysiology had advanced enough to provide for the first time the required technology. At the time of their initial publication, they had probably already performed surgery for psychiatric illness, pain, movement disorders, and aspiration of tumor cysts. The first decade after their publication was a remarkably productive time for them and the other pioneers who entered the field.
Lesioning the Thalamus for Dyskinesia
Authors: Ohye Chihiro , Shibazaki Tohru
Published: April 2003

Recent advances on understanding the pallidothalamic relation lead us to perform Vim-Vo thalamotomy (combined thalamic lesion in ventralis intermedius nucleus and ventralis oralis nucleus) for cases with dyskinesia. In our recent series of thalamotomies, there are 12 cases of dyskinesia caused by various etiologies. Therefore the clinical manifestation of the involuntary movement was different in each case, including, more or less, some elements of irregular involuntary hyperkinetic movement. Stereotactic operation was performed using Leksell’s apparatus aided by Surgiplan and MRI. The Vim nucleus was identified by physiological study using microelectrodes. High background activity and kinesthetic neurons are reliable indicators of Vim nucleus (but only for the lateral part). Then, selective coagulation was made by dual coagulation needles. Since the Vo nucleus is located just rostral to the Vim nucleus, the coagulation needle was turned toward the anterior part to partly cover the Vo nucleus. Thus, selective Vim-Vo thalamotomy was shown to be quite successful for the treatment of dyskinesia.
Microanatomy of Medial Temporal Area and Subtemporal Amygdalohippocampectomy
Authors: Hori Tomokatsu , Yamane Fumitaka , Takenobu Atsumi
Published: April 2003

For seizure control in temporal lobe epilepsy, the head of the hippocampus to the choroidal point, parahippocampal gyrus, entorhinal area, uncus, and at least the basolateral nucleus of the amygdala should be completely removed. The subtemporal approach should be selected for removal of these structures, and it does not interrupt the temporal stem and optic radiation. Pre- and postoperative neuropsychological examinations revealed that there is no significant decline of scores of various examinations including WAIS, WMS, Randt memory, and verbal associates learning tests, even if the resection were performed on the language dominant side. Seizure control for the 20 non-lesional patients operated with this approach is 60% (Class I and II), without definite permanent complications.
The Optimal Stimulation Site for Chronic Stimulation of the Subthalamic Nucleus in Parkinson’s Disease
Authors: Yokoyama Tetsuo , Sugiyama Kenji , Nishizawa Shigeru , Yokota Naoki , Ohta Seiji , Akamine Souichi , Namba Hiroki
Published: April 2003

To determine the optimal stimulation site within the subthalamic nucleus (STN), monopolar stimulation of four electrode contacts and the resulting effects on parkinsonian symptoms were evaluated in 10 consecutive patients. The UPDRS score for rigidity and akinesia improved significantly after stimulation at each of the contacts, compared to the pre-evaluation state (Fisher’s test, p < 0.05). The most significant improvement was obtained after stimulation at contact-2 (rigidity: 74.4 ± 20.4%, akinesia: 53.7 ± 14.3%) (Fisher’s test, p < 0.001). Contact-2 was located at the dorsal border of the STN at a mean distance of 0.3 ± 0.7 mm. DBS at the dorsal border of the STN, where the stimulation affects the neurons as well as their axonal fibers, produces the greatest clinical improvement in parkinsonian symptoms.
Microvascular Decompression for Hemifacial Spasm: A Long-Term Follow-Up of 1,169 Consecutive Cases
Authors: Chung Sang Sup , Chang Jong Hee , Choi Jae Young , Chang Jin Woo , Park Young Gou
Published: April 2003

We analyzed the records of 1,169 patients with hemifacial spasm (HFS) who underwent microvascular decompression (MVD) and were followed up for more than 6 months from January 1987. The mean follow-up duration was 23.8 months (6–145 months). Excellent surgical outcome was obtained in 90.5% and good in 4.5%, giving an overall success rate of 95.0%. There was statistically significant relationship between vertebral artery (VA) shift and side of symptom. Permanent facial weakness and hearing impairment were 1.4% and 2.3%, respectively. There were no anatomical differences at the root entry zone (REZ) and significant differences of surgical outcome in young HFS (34 patients). Factors such as type of offender, severity of compression on the facial nerve root, and the degree of decompression of the REZ on postoperative MRI did not correlate with surgical outcome.
Prevention and Detection of Diabetic Embryopathy
Authors: McLeod Lynne , Ray Joel G.
Published: April 2003

Congenital anomalies are more common in the offspring of women with type 1 and type 2 diabetes mellitus. Herein we define those anomalies more commonly found in the offspring of women with diabetes mellitus, and examine the role of hyperglycemia in their pathogenesis. We then discuss methods for the optimal screening and detection of embryopathy. We conclude by presenting evidence in support of preconception diabetes care to lower the risk of fetal anomalies in women with diabetes mellitus.
Molecular and Cellular Basis of Isolated Dominant-Negative Growth Hormone Deficiency, IGHD Type II: Insights on the Secretory Pathway of Peptide Hormones
Authors: Mullis Primus-E. , Deladoëy Johnny , Dannies Priscilla S.
Published: April 2003

Estimates of the frequency of GH deficiency range from 1:4,000 to 1:10,000. Most cases are sporadic and presumed to be secondary to a wide variety of aetiologies. However, in families with consanguinity, or when a second case occurs in the same family, a genetic cause may be suspected. Given that the patient is isolated GH deficient four distinct familial types of isolated GH deficiencies (IGHD) are well-differentiated on the basis of inheritance, hormonal deficiencies as well as molecular analyses. Two forms are autosomal recessively (IGHD type IA and IB), one is autosomal dominantly (IGHD type II) and one X-linked inherited. In this review, we focus on the secretory pathway of peptide hormones in general and on the possible mechanisms causing IGHD type II in detail. Most interestingly, in IGHD type II the apparently same phenotype of IGHD is caused by distinct GH-1 gene alterations leading to different blockades within the secretory pathway. Furthermore, this type of IGHD, in addition to some other specific GH-1 gene mutations, provides the most important opportunity to shed light on cell-biological mechanisms far beyond its pure description at the DNA/RNA level.
Clinical Significance of the Antibody against Oxidized Low-Density Lipoprotein in Acute Myocardial Infarction
Authors: Inoue Teruo , Yaguchi Isao , Uchida Toshihiko , Kamishirado Hirotoshi , Nakahara Shiro , Hayashi Terumi , Morooka Shigenori
Published: April 2003

To establish the clinical significance of the antibody against oxidized low-density lipoprotein (anti-Ox-LDL) titer in patients with acute myocardial infarction (AMI), we measured the anti-Ox-LDL titer in 39 patients with AMI and 25 controls. In all AMI patients, the anti-Ox-LDL titer on admission was higher (p < 0.05) than the value in the controls. One month after admission, the titer decreased significantly (p < 0.001) reaching control levels. In patients who underwent thrombolytic therapy, the anti-Ox-LDL titer on admission was identical in patients with occluded infarct-related arteries (IRA) and patients with patent IRA during emergency coronary angiography. In patients who did not undergo thrombolytic therapy, the anti-Ox-LDL titer on admission was higher in patients with occluded IRA than in patients with patent IRA. An increased anti-Ox-LDL titer may be a risk factor for the onset of AMI. Spontaneous recanalization of the IRA may be associated with increased anti-Ox-LDL titers, while thrombolysis-induced recanalization may be independent of it.
Isolated Left Ventricular Noncompaction: An Unclassified Cardiomyopathy with Severe Prognosis in Adults
Authors: Rigopoulos Angelos , Rizos Ioannis K. , Aggeli Constadina , Kloufetos Periklis , Papacharalampous Xenophon , Stefanadis Christodoulos , Toutouzas Pavlos
Published: April 2003

Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy, which appears to represent an arrest in intrauterine endomyocardial morphogenesis. It is diagnosed both in children and adults. Its common presentation involves heart failure symptoms, ventricular tachyarrhythmias and thromboembolic events, but the age of onset varies widely. The diagnosis is made by the combined appearance of numerous, excessively prominent trabeculations and multiple deep intertrabecular recesses perfused from the ventricular cavity, commonly involving the apical and midventricular segments of the left ventricle. Although the peculiar echocardiographic picture may possibly lead to the correct diagnosis, this condition may be often misdiagnosed or unrecognized since it is not widely known.
Unusual Myelodysplastic Syndrome with the Initial Presentation Mimicking Idiopathic Thrombocytopenic Purpura
Authors: Kuroda Junya , Kimura Shinya , Kobayashi Yutaka , Wada Katsuya , Uoshima Nobuhiko , Yoshikawa Toshikazu
Published: April 2003

Idiopathic thrombocytopenic purpura (ITP) and primary myelodysplastic syndrome (MDS) are hematological disorders that are frequently associated with thrombocytopenia, and both are heterogeneous disorders of uncertain etiology. Their diagnosis requires the exclusion of other hematological or immunological disorders whose diagnosis is usually not difficult. However, in some patients presenting with thrombocytopenia, the differential diagnosis is complex. We performed a retrospective study of 47 consecutive patients treated between 1990 and 2001; in 25 patients the initial diagnosis was ITP, in 22 it was MDS; we compared their backgrounds, laboratory data and clinical outcomes. Among the 25 ITP patients, there were 5 confusing cases. Following treatment, they presented with inexplicable refractory anemia and/or neutropenia. Cytopenia, the polyploidization pattern of megakaryocytes, and chromosomal aberrations were of diagnostic relevance in these patients’ defective hematopoiesis. Their cytopenia progressed relatively slowly and none progressed to leukemic transformation. We suggest that these 5 patients should be classified into an unusual subtype of MDS with clinical characteristics resembling ITP.
Pure or Predominantly Sensory Transient Ischemic Attacks Associated with Posterior Cerebral Artery Stenosis
Authors: Kim Jong S.
Published: April 2003

Pure or predominantly sensory transient ischemic attacks (ps-TIAs) are uncommon, and underlying vascular abnormalities have rarely been described. The author reports 5 patients with TIAs which were of short duration, stereotypical and purely or predominantly sensory in nature. Brain MRI did not reveal any lesions, while angiography demonstrated focal stenoses in the proximal portion of the posterior cerebral artery (PCA). It is concluded that ps-TIAs strongly suggest the presence of PCA disease. Repeated compromise of small vessels supplying the posterior-lateral part of the thalamus seems to be the pathogenic mechanism.
Iatrogenesis or Bad Luck? Relapse of an LMP1-Positive Follicular Lymphoma after Immunosuppression for Hepatitis-Associated Aplastic Anaemia
Authors: Krsnik Isabel , García-Suárez Julio , López-Rubio Montserrat , Santana Alicia
Published: April 2003

A 55-year-old man suffered a cutaneous relapse of an LMP1-positive follicular lymphoma after treatment with antithymocyte globulin and cyclosporine A (CSA) for a hepatitis-associated aplastic anaemia (AA). Rituximab was not effective, so CSA was tapered off. Lymphoma masses did not regress but AA relapsed. A second remission of both lymphoma and AA was achieved with high-dose cyclophosphamide, but the patient died of a bilateral pneumonia. The relationships between immunosuppression, viral reactivation and tumour growth are discussed. The use of rituximab and lamivudine in immunodepressed patients is also commented.
Evaluation of Tumor Necrosis Factor-α and Erythropoietin Serum Levels in B-Cell Chronic Lymphocytic Leukemia Patients with Anemia
Authors: Capalbo Silvana , Battista Cosima , Delia Mario , Ciancio Angela , De Santis Gaetano , Dargenio Michela , Diomede Daniela , Liso Vincenzo
Published: April 2003

Serum levels of tumor necrosis factor-α (TNF-α) and of erythropoietin (Epo) have been evaluated in 100 patients with B-cell chronic lymphocytic leukemia (CLL) in order to determine whether these factors could be significant in the development of anemia, which was observed in some cases with advanced disease. In our series of patients, TNF-α serum levels had an inverse correlation with hemoglobin levels (r = –0.813). In patients with anemia, the serum levels of TNF-α were significantly higher (p = 0.022) than in those without anemia (186.7 ± 84.7 vs. 39.8 ± 20.7 pg/ml). Serum Epo levels were also significantly (p = 0.0003) increased in CLL patients with anemia compared to those without (134.1 ± 225.9 vs. 12.3 ± 4.8 mU/ml). The ratio of observed/predicted (O/P) serum Epo was adequate (>0.8) for the degree of anemia in 70% of patients with anemia and inadequate in the remaining 30%. In the latter, the mean serum TNF-α level was significantly higher (p = 0.005) than the mean for the anemic cases with an adequate O/P ratio of serum Epo (234.1 vs. 166.4 pg/ml). These data suggest that although CLL anemia is not characterized by inadequate Epo production, in some CLL patients this factor may be correlated. In these cases, the levels of TNF-α were significantly higher than in other anemic cases. Compared to other CLL patients with anemia, these CLL patients might better respond to therapy with recombinant human Epo in pharmacological doses.
Cytogenetic and Molecular Genetic Aspects of Essential Thrombocythemia
Authors: Steensma David P. , Tefferi Ayalew
Published: April 2003

Essential thrombocythemia (ET) is a chronic myeloid disorder that is characterized by thrombocytosis, thrombohemorrhagic and vasomotor symptoms, a long median survival, and a low risk of transformation to leukemia. ET can be difficult to distinguish from secondary (reactive) thrombocytosis, and the diagnosis of ET can only be made after the exclusion of other marrow disorders with similar features. Although ET has been assumed to be a clonal process, recent studies have suggested that a substantial number of cases classified as ET may actually not be clonal, and nonclonality may be associated with a lower risk of thrombosis. The lack of a characteristic cytogenetic marker for ET confounds analyses of clonality and offers no insight into disease pathogenesis. There is controversy over the proper classification of thrombocytosis associated with the pathological BCR-ABL gene rearrangement; such cases are not clearly distinguishable from chronic myelogenous leukemia (CML) and should be provisionally classified as CML. New insights are emerging into the role of the megakaryocytopoiesis regulator thrombopoietin (TPO) and its receptor, c-Mpl, in ET and related disorders, but TPO-Mpl dynamics appear to be complex. In some familial thrombocythemic syndromes, mutations in the 5′ untranslated region of TPO have recently been described, but these have not yet been observed in sporadic ET. In the future, global analysis of gene expression patterns may help overcome diagnostic dilemmas, refine disease classification, and lead to an improved understanding of the pathogenesis of ET.
Role of Interleukin-6 in Growth Failure: An Animal Model
Authors: De Benedetti Fabrizio , Meazza Cristina , Martini Alberto
Published: April 2003

Indirect evidence suggests a link between factors produced during the inflammatory response and stunted growth. The demonstration of this link was provided by the observation that mice transgenic for the inflammatory cytokine interleukin-6 (IL-6), expressing high circulating levels of IL-6 since birth, show a marked decrease in growth rate leading to adult mice 50–70% the size of wild-type littermates. The growth defect is completely abolished by neutralization of IL-6. In these mice the production of GH is normal, while circulating levels of IGF-I are markedly decreased. Administration of IL-6 to wild-type mice results in a marked decrease in IGF-I levels. These observations show that in vivo high levels of IL-6 are associated with low levels of IGF-I. However, IL-6 does not directly affect IGF-I production both in vitro and in vivo. In contrast, markedly decreased levels of IGFBP-3 are present in the IL-6 transgenic mice and administration of IL-6 to wild-type mice results in a marked decrease in IGFBP-3 levels. In these mice the decrease in IGFBP-3 levels is associated with impaired formation of the 150 kD ternary complex, even in the presence of normally functional ALS. As a consequence, IL-6 transgenic mice show increased clearance of circulating IGF-I, suggesting that IL-6 decreases IGF-I levels by increased clearance. Proteolytic degradation of IGFBP-3 occurs in the IL-6 transgenic mice, suggesting that the decrease in IGFBP-3 could be at least in part due to proteolysis. The abnormalities of the IGF-I system observed in the IL-6 transgenic mice are similar to those found in patients with systemic juvenile idiopathic arthritis, one of the chronic inflammatory diseases characterized by stunted growth and prominent production of IL-6. The IL-6 transgenic mice represent a faithful animal model of the growth impairment associated with chronic inflammation and may therefore provide information relevant to the understanding and treatment of this complication of inflammatory diseases.
Mechanisms Influencing Bone Metabolism in Chronic Illness
Authors: Daci E. , van Cromphaut S. , Bouillon R.
Published: April 2003

Bone is permanently renewed by the coordinated actions of bone-resorbing osteoclasts and bone-forming osteoblasts, which model and remodel bone structure during growth and adult life. The origin of osteoblastic cells (osteoblasts, osteocytes and bone-lining cells) differs from that of osteoclasts, but both cell groups communicate with each other using cytokines and cell-cell contact as to optimally maintain bone homeostasis. This communication in many ways uses the same players as the communication between cells in the immune system. During acute life-threatening illness massive bone resorption is the rule, while bone formation is suppressed. During chronic illness, the balance between bone formation and bone resorption also shifts, frequently resulting in decreased bone mass and density. Several factors may contribute to the osteopenia that accompanies chronic illness, the most important being undernutrition and low body weight, inflammatory cytokines, disorders of the neuroendocrine axis (growth hormone/IGF-1 disturbances, thyroid and gonadal deficiency), immobilization, and the long-term use of glucocorticoids. Their combined effects not only influence the generation and activity of all bone cells involved, but probably also regulate their life span by apoptotic mechanisms. Osteopenia or even osteoporosis and bone fragility, and before puberty also decreased linear growth and lower peak bone mass are therefore frequent consequences of chronic illnesses.
Growth in Paediatric Crohn’s Disease
Authors: Cezard J.P. , Touati G. , Alberti C. , Hugot J.P. , Brinon C. , Czernichow P.
Published: April 2003

Growth failure (GF) is one of the major complications affecting children with inflammatory bowel disease. The faltering is temporary in 40–50% of cases and prolonged in 10–20% in Crohn’s disease (CD). Such failure is rare in children with ulcerative colitis (5%). This complication is often associated with retarded bone development and delayed onset of sexual maturation. The delayed linear growth has a variety of causes including insufficient intake due to anorexia and the inflammatory process with increased energy and protein expenditure. Other factors are increased intestinal loss, secondary hypopituitarism and treatment with steroids. Therapeutic strategies of CD in children have changed this last decade by introducing new therapeutic agents such as topic steroids, immunosuppressors, anti-TNF (antibody and notably in children enteral nutrition which has shown its efficacy in inducing remissions of active CD, restoring nutritional status and stimulation of linear growth. The results of a recent prospective multicentric study over 2 years in 82 CD show that severe GF (–2 SD) is initially present in 15% (n = 12), among them 11 remain < –2SD after 2 years of follow-up. Six patients who were on the normal range initially increased their GF during the follow-up (< –2SD) (total 21% < –2SD (n = 17) at 2 years). At inclusion in this group there was no difference in growth velocity, used of steroids, enteral nutrition or severity of CD as compared to the group with no GF. It suggests that new treatment strategy should be developed in the future for this specific complication of paediatric CD.