bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Related Modifications of Circadian Rhythm of Serum Leptin in Healthy Men
Authors: Zhao Zi-Yan , Fu Yue-Rong , Li Xin-Hua , Li Yu-Yang , Bogdan André , Touitou Yvan
Published: April 2003

Background: Leptin, the product of the ob gene, is secreted by the adipocyte and is involved in the regulation of body weight, energy homeostasis and a wide spectrum of biological activities. Objective: We studied how variations in circadian serum leptin levels change as people age. Methods: Serum leptin levels were studied on a circadian basis in 26 men, 6 overweight (BMI >27.8) and 20 with normal weight. The normal-weight men were divided into four age groups: (A) in their 30s, (B) in their 40s, (C) in their 50s, and (D) in their 60s. Serum samples were drawn at 2-hour intervals from 8:00 to 22:00 and hourly from 22:00 to 8:00 for a total of 24 h. Results: A significant circadian variation of leptin levels was found whatever the age with a peak at night and a trough around noon. The circadian leptin levels were higher in the older normal-weight groups (50s and 60s) and in the groups with a BMI >27.8. Conclusion: Our study demonstrates that changes in the characteristics of the circadian rhythm of serum leptin in healthy men are associated with both advancing age and increased BMI.
Serum Levels of Antibodies Against Oxidised LDL in Kidney Graft Recipients
Authors: Zezina Lilija , Dimény Emöke , Vessby Bengt , Fellström Bengt
Published: April 2003

Background/Aims: Lipid abnormalities present in the post-transplant period may contribute to the development and progression of complications leading to graft and patient loss. In the present study serum levels of antibodies against oxidised LDL (Ab-oxLDL) in kidney graft recipients were investigated along with their possible relation to the development of complications in the post-transplant period, and to the outcome of kidney transplantation. Methods: Serum levels of Ab-oxLDL and lipid pattern were evaluated in 92 kidney graft recipients before and at 3, 6, 12, and 24 months after kidney transplantation, as well as in 90 healthy blood donors (control group). Results: Kidney graft recipients had higher frequency of low levels of Ab-oxLDL as compared with the control group. A decrease in Ab-oxLDL levels was observed at 6 months post-transplant. Patients with early graft loss due to acute rejection had lower pre-transplant Ab-oxLDL levels (p < 0.05) as compared to patients with graft survival >3 months. Conclusions: It is suggested that decreased Ab-oxLDL levels found in kidney graft recipients may reflect impaired response to the products of lipid oxidation or increased consumption of Ab-oxLDL, and are associated with graft loss due to acute rejection.
Induction of α-Catenin, Integrin α3, Integrin β6, and PDGF-B by 2,8-Dihydroxyadenine Crystals in Cultured Kidney Epithelial Cells
Authors: Wang Li , Raikwar Nandita , Yang Min , Deng Li , McAteer James A. , Stambrook Peter J. , Sahota Amrik , Tischfield Jay A.
Published: April 2003

Background: Homozygous adenine phosphoribosyltransferase (APRT) deficiency is associated with 2,8-dihydroxyadenine (DHA) nephrolithiasis. Using whole kidney RNA from Aprt knockout mice, we previously showed that the renal deposition of DHA leads to changes in the expression of genes involved in tissue injury. To determine the cellular basis for these changes, we investigated gene expression in cultured human kidney (NHK-C) and African green monkey (BSC-1) epithelial cells exposed to DHA or calcium oxalate monohydrate (COM) crystals. Methods: First-strand cDNAs, synthesized from mRNA isolated from treated and untreated cells, were hybridized to membrane-bound cDNA arrays containing 588 genes associated with various physiological and pathological processes. Changes in gene expression were confirmed by reverse transcription PCR. Results: Twenty-seven percent of the array cDNAs were expressed in untreated NHK-C cells at varying levels relative to a housekeeping gene. The expression of three adhesion molecules (α-catenin, integrin α3, and integrin β6) and platelet-derived growth factor B (PDGF-B) was elevated following exposure of NHK-C cells to DHA. Increased expression of the adhesion molecules was also observed in BSC-1 cells, but PDGF-B expression could not be detected. COM crystals also stimulated the expression of these four genes in NHK-C cells, but the expression profile was quantitatively different compared with DHA. Conclusions: These findings suggest that DHA crystals stimulate the expression of specific genes in kidney epithelial cells and that the pathways for DHA-induced cell injury may be similar to those for COM crystals. The induction of adhesion molecules and PDGF-B may affect cell-cell or cell-matrix interactions and/or alter the actin cytoskeleton. These alterations may ultimately contribute to crystal-induced renal injury.
Mixed Bone Marrow or Mixed Stem Cell Transplantation for Prevention or Treatment of Lupus-Like Diseases in Mice
Authors: Good Robert A. , Wang Bing-Yan , El-Badri Nagwa S. , Steele Ann , Verjee Tazim
Published: April 2003

Scientific analyses fortified by interpretations of immunodeficiency diseases as ‘experiments of nature’ have revealed the specific immune systems to be comprised of T cells subserving cell-mediated immunities plus B cells and plasma cells which produce and secrete antibodies. These two separate cellular systems regularly interact with each other to produce a coordinated defense which permits mammals to live within a sea of microorganisms that threaten the integrity and the survival of individuals. We have shown that bone marrow transplantation (BMT) can be used as a form of cellular engineering to construct or reconstruct the immune systems and cure otherwise fatal severe combined immunodeficiency. When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW × BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus allogeneic (normal healthy) BMT or mixed peripheral blood HSCT. Thus, the most complex autoimmune diseases can be prevented or cured in experimental animals by mixed syngeneic plus allogeneic BMT or HSCT which produce stable mixed chimerism as a form of cellular engineering.
Calcium Homeostasis and Imbalance
Authors: Fukagawa Masafumi , Kurokawa Kiyoshi
Published: April 2003

The human body is equipped with an efficient protection system against hypocalcemia. This system is composed of parathyroid glands, bone, kidney, and intestine. By appropriate actions of parathyroid hormone (PTH) and active vitamin D (1,25-dihydroxyvitamin D), a small fall of extracellular calcium ion concentration is instantly corrected. Thus, a defect of any step in this system results in the development of hypocalcemia. Overloaded calcium either from bone or intestine is efficiently excreted into the urine. Thus, hypercalcemia develops almost exclusively when a greater amount of calcium than the kidney can excrete is loaded. In chronic dialysis patients, either hypocalcemia or hypercalcemia may develop because of defects in these two defense systems against calcium imbalance.
Spontaneous Abortions in Couples Declining Multifetal Pregnancy Reduction
Authors: Evans Mark I. , Wapner Ronald J. , Ayoub Melissa A. , Shalhoub Alex G. , Feldman Baruch , Yaron Yuval
Published: April 2003

Multifetal pregnancy reduction (MFPR) has clearly improved the outcomes of multifetal gestations. Several recent reports have also suggested improved outcomes in nonreduced cases, but there have been methodologic concerns about the denominators, i.e. have all cases been included and is there a ‘hidden mortality’ of unknown lost cases. Here we assessed the outcome of patients telephoning to discuss MFPR, but who chose not to have the procedure. Over a 3-year period, 446 patients had MFPR by one operator. Nineteen patients chose not to have the procedure. There were 11 preterm births, 1 term delivery, and 5 spontaneous losses (7 of 17) prior to 24 weeks, a loss rate of 35%. Two patients delivering triplets had a loss of 1 fetus/neonate. These data suggest that the loss rates of nonreduced pregnancies may be higher than generally thought, making the improvements with MFPR even bigger than generally realized.
Asymmetry of Tonsillar Ectopia in Chiari I Malformation
Authors: Tubbs R. Shane , Wellons III John C. , Oakes W. Jerry
Published: April 2003

There has been almost no evaluation or discussion of the symmetry of tonsillar ectopia in the medical literature. We measured the degree of left and right tonsillar herniation in 42 pediatric patients with a symptomatic Chiari I malformation and made clinical/radiological correlations. 18% of all patients with tonsillar asymmetry had clinical symptoms or physical findings referable to the inequality of their hindbrain herniation. In addition, 95% of patients with a coexisting syringomyelia had a right cerebellar tonsillar herniation greater than the left. We hypothesize that slight differences in posterior cranial fossa morphology may physically allow for greater unilateral herniation of the left or right cerebellar tonsil, which may be manifested in a patient’s clinical presentation.
Risperidone Treatment of Schizophrenia: Improvement in Psychopathology and Neuropsychological Tests
Authors: Borkowska Alina , Araszkiewicz Aleksander , Rajewski Andrzej , Rybakowski Janusz K.
Published: April 2003

The aim of the study was to assess the effects of short-term risperidone treatment on schizophrenic symptoms and on neuropsychological frontal tests, and to find an association between the improvements in these two kinds of domains. Twenty-two schizophrenic patients treated with risperidone (2–6 mg/day) for 4 weeks were studied. Treatment with risperidone resulted in a significant decrease in the intensity of schizophrenic symptoms and in an improvement in all neuropsychological tests applied. A robust correlation was obtained between the amelioration of negative symptoms and improvements in many neuropsychological tests, specifically with amelioration in the Wisconsin Card Sorting Test (WCST), perseverative errors. Some correlation was also found with the improvement of positive symptoms, specifically with amelioration in the WCST, completed categories. The results may suggest a common neurobiological substrate of negative and cognitive symptoms, reflected in prefrontal cortex pathology and in therapeutic response to atypical antipsychotics.
The Association between Disease Severity and Sleep-Related Problems in Patients with Parkinson’s Disease
Authors: Happe Svenja , Lüdemann Peter , Berger Klaus
Published: April 2003

Although sleep-related problems are a frequent finding in patients with Parkinson’s disease (PD), the aetiology is still unknown. We examined the associations between disease severity, sleep-related problems and social status in 116 PD patients participating in the FAQT Study, a prospective, German cohort study evaluating determinants of quality of life in PD patients. 47.4% of the patients reported sleep onset difficulties, 26.7% sleep interruptions, 14.7% had five or more sleep-related events during the night and 71.6% showed symptoms of increased daytime somnolence. The disease severity was significantly associated with sleep-related events (p = 0.01), the depression score with sleep onset difficulties (p = 0.04), sleep interruptions (p = 0.01) and the levodopa dose (p < 0.01). We conclude that depressive symptoms and increasing levodopa doses in PD patients mainly cause sleep onset difficulties and sleep interruptions, while the severity of motor symptoms contributes to sleep-related events like sleep walking, heavy sweating and nightmares.
Effects of Lesions of Hippocampal Fields CA1 and CA3 on Acquisition of Inhibitory Avoidance
Authors: Martínez Isabel , Quirarte Gina L. , Díaz-Cintra Sofía , Quiroz César , Prado-Alcalá Roberto A.
Published: April 2003

Performance decrements of inhibitory avoidance (IA) induced by lesions in either the dorsal or ventral hippocampus have been interpreted as a deficiency in acquisition. Alternative interpretations are that short-term learning occurs despite the lesions and the long-term performance decrements reflect a failure of consolidation or retrieval. To assess the alternative explanations of the performance decrements, rats received lesions in either CA1 or CA3 fields of dorsal and ventral hippocampus, respectively, 8 days before IA training. Retention was tested at 30 min or 24 h after training. Kainic acid lesions were also produced in either hippocampal field 1 day after training and retention measured 8 days later. The group assessed 30 min after IA training showed little or no performance decrements, whereas the remaining groups did show marked performance decrements. These results do not support the conclusion that the hippocampus is essential for acquisition and support the idea that the hippocampus is highly involved in the consolidation or retrieval of information germane to these procedures.
A Dose-Escalation Study of Oxaliplatin and Vinorelbine in Patients with Advanced Solid Tumors
Authors: Kakolyris S. , Kouroussis C. , Koukourakis M. , Mavroudis D. , Malas K. , Vardakis N. , Bozionelou V. , Kalbakis K. , Georgoulias V.
Published: April 2003

Objectives: Vinorelbine (V) and oxaliplatin (OX) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors. Patients and Methods: Thirty-eight patients with histologically confirmed non-small-cell lung cancer, ovarian cancer and breast cancer who had failed at least one prior chemotherapy regimen were enrolled. The patients’ median age was 60 years, 33 were female, and 27 had a performance status (WHO) of 0–1. V was administered on days 1 and 8 as a 1-hour intravenous infusion at escalated doses ranging from 20 to 27 mg/m2. OX was administered on days 1 and 8 at escalated doses ranging from 40 to 55 mg/m2, following V administration. Treatment was repeated every 3 weeks. Results: At the dose of V 27 mg/m2 and OX 55 mg/m2 3 out of 6 enrolled patients presented DLTs (2 patients grade 4 neutropenia and 1 treatment delay at day 8), and, thus, the recommended MTD for future phase II studies are V 27 mg/m2 and OX 50 mg/m2. A total of 131 treatment cycles were administered. Grade 3/4 neutropenia complicated 23 (18%) treatment cycles. There was one septic death. The main nonhematologic toxicities were grade 2/3 nausea/vomiting (17 cycles; 13%), grade 2 neurotoxicity (6 cycles; 5%) and grade 2/3 asthenia (21 cycles; 16%). One CR (4%), 5 PR (20%) and 4 SD (16%) were observed amongst the 25 evaluable patients. All responses were observed in patients with ovarian and breast cancer. Conclusions: The results of this phase I study demonstrate that V and OX can be combined at clinically effective and relevant doses to be further evaluated in patients with breast and ovarian cancer.
Second-Line Chemotherapy with a Hybrid-Alternating Regimen of Bolus 5FU Modulated by Methotrexate and Infusional 5FU Modulated by Folinic Acid in Patients with Metastatic Colorectal Cancer Pretreated with 5FU
Authors: Carlomagno C. , Lauria R. , De Laurentiis M. , Arpino G. , Massarelli E. , Ferrara C. , Milano A. , Vernaglia Lombardi A. , Costanzo R. , Catalano G. , Bianco A.R. , De Placido S.
Published: April 2003

Background and Aim: In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer. Patients and Methods: Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations. Results: 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03–7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8–21.9). Toxicity was mild. Conclusions: The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.
A Phase I Study of Weekly Docetaxel, 24-Hour Infusion of High-Dose Fluorouracil/Leucovorin and Cisplatin in Patients with Advanced Gastric Cancer
Authors: Chen Li-Tzong , Liu Tsang-Wu , Wu Chew-Wun , Chung Tsai-Rong , Shiah Her-Shyong , Jan Chang-Ming , Liu Jacqueline Ming , Whang-Peng Jacqueline , Chang Jang-Yang
Published: April 2003

Objectives: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of both docetaxel and 5-fluorouracil (5-FU) when administered weekly in a regimen of docetaxel, 5-FU/leucovorin and cisplatin (DFLP) for 2 consecutive weeks every 3 weeks. Patients and Methods: A total of 31 patients with chemo-naive, advanced adenocarcinoma of the stomach were enrolled in the study. Cisplatin and leucovorin dosages were fixed throughout the study at 30 and 300 mg/m2, respectively. 5-FU dosage was fixed at 1,600 mg/m2 while docetaxel was evaluated at weekly 1-hour infusion dosages of 30, 40 and 50 mg/m2 to determine the MTD. Cisplatin, 5-FU and leucovorin were administered together as a 24-hour continuous infusion following docetaxel. Weekly 5-FU dosages of 1,600, 2,000 and 2,400 mg/m2 were then evaluated after setting the docetaxel dosage at the MTD. Results: A total of 95 chemotherapy cycles were administered, with a median of three cycles per patient. The MTD of docetaxel was defined at 40 mg/m2. At a docetaxel dosage of 50 mg/m2 per week, the dose-limiting events of grade 4 febrile neutropenia and grade 3 hypomagnesemia occurred. With fixation of docetaxel to 40 mg/m2, the DLT for 5-FU was found at 2,400 mg/m2 per week. This incurred grade 4 neutropenia such that the MTD of 5-FU was defined at 2,000 mg/m2. Grade 3/4 neutropenia occurred in 14 patients (45%), with 2 patients developing febrile neutropenia. Grade 2 and 3 hypomagnesemia and hypokalemia occurred in 9 (41%) and 4 (18%) patients, respectively, of the first 22 patients treated with a 24-hour infusion of cisplatin and 5-FU/leucovorin immediately following docetaxel. Following a change in the cisplatin administration schedule to a 3-hour infusion after 5-FU/leucovorin infusion, no such complications were observed in 9 subsequently treated patients. Grade 2 diarrhea was recorded in 11 patients (35%). Grade 2/3 asthenia occurred in 9 patients (30%), which resolved after correction of electrolyte disorders. Twenty-six patients were assessable for response analysis. There were 2 (7.8%) complete and 14 (53.8%) partial responses, with the overall response rate being 61.5% (95% confidence interval, 41.5–81.6%). Responses were observed at all dose levels. Conclusion: Two consecutive weeks of DFLP infusions every 3 weeks appear to be an active regimen with a tolerable toxicity profile in advanced gastric cancer. For further phase II studies, the recommended dose for this combination is 40 mg/m2 of docetaxel and 2,000 mg/m2 of 5-FU per week.
Anti-p53 in Breast Cancer: Concordance of Different Assay Procedures and Association with p53 Antigen Expression
Authors: Volkmann Martin , Sinn Hans-Peter , Gaugel Dirk , Frey Manfred , Hajjar Yaser , Ludwig Jochen , Hänsel Susanne , Bastert Gunther , Wallwiener Diethelm , Fiehn Walter , Zentgraf Hanswalter , Huober Jens
Published: April 2003

Objective: Anti-p53 levels detected by different methods were compared in a predefined group of patients with breast cancer and correlated with p53 antigen expression in the corresponding tumors. Methods: P53 autoantibodies were investigated in 165 patients with primary breast cancer using ELISAs with recombinant or native p53. Immunoblot and indirect immunofluorescence (Huh7) were used for confirmation, p53 antigen expression in the tumor was determined immunohistochemically. Results: Using ELISA, overall 18/165 positives (11%) were detected, with only partly concordant results between the assays. Five positive sera were confirmed by immunoblot, and three also by indirect immunofluorescence. Anti-p53-positive patients detected by more than two assays showed accumulated p53 in the tumor (6/6) and mostly suffered from recurrent tumors (4/6; p = 0.02). In these cases, a trend towards a shortened disease-free interval was found (26 vs. 49 months; n.s.). In patients with a positive or borderline result in only one of the serological methods, there was no increased rate of p53 accumulation compared to anti-p53-negative patients (4/19 versus 35/126). Conclusions: Lack of assay standardization may partly explain the divergence in reports on anti-p53 and its clinicopathological associations. We speculate that, in different groups of patients, anti-p53 might be induced by different mechanisms.
Growth Hormone Deficiency: Permanence and Diagnosis in Young Adults
Authors: Castro C. , Trivin C. , Souberbielle J.-C. , Zerah M. , Brauner R.
Published: April 2003

Objective: To optimize the tools for diagnosing idiopathic growth hormone (GH) deficiency. Methods: We compared the data of 43 young adults treated for GH deficiency before and after GH treatment and puberty. Those with organic lesions were assigned to group 1 (n = 9), those with certain GH deficiency (n = 11) to group 2 and those with no criterion of certitude of GH deficiency to group 3 (n = 23). Results: Group 1 patients: the GH peaks at first [1.5 ± (SE) 0.4 µg/l] and second (1.9 ± 0.7 µg/l) evaluations before treatment were similar to those at the third evaluation (1.2 ± 0.8 µg/l) after treatment. Group 2 patients: they had similar peaks (2.6 ± 0.8, 2.9 ± 0.5 and 5.5 ± 1.4 µg/l). Group 3 patients: the peaks increased from 4.9 ± 0.4 and 4.8 ± 0.4 to 18.4 ± 2.3 µg/l (p < 0.0001); 87% had a GH peak >10 µg/l at this evaluation. The plasma insulin-like growth factor 1 was initially below –2 z-score in 12/13 of these patients and similarly low in 4/17 patients at the third evaluation. The growth rates of the three groups before and their increase during the 1st year of treatment were similar. Conclusion: Almost all patients with GH deficiency before puberty without criteria of certitude had a normal GH peak after puberty. Some of these patients probably had a transiently low GH secretion.
Management of Congenital Adrenal Hyperplasia: Results of the ESPE Questionnaire
Authors: Riepe Felix G. , Krone Nils , Viemann Matthias , Partsch Carl-Joachim , Sippell Wolfgang G.
Published: April 2003

The management of children and adolescents with congenital adrenal hyperplasia (CAH) remains difficult. To assess the current European practice in diagnosis and management of CAH, an ESPE (European Society for Paediatric Endocrinology) survey was circulated in 2000/2001. The questionnaire was answered by 34% of ESPE members, representing 125 institutions which cared for 6,553 CAH patients. Paediatric endocrinologists, surgeons, gynaecologists, geneticists, and psychologists are involved in the immediate care of the CAH neonate and his family. 44% of centres take part in neonatal screening programmes. In families at risk, prenatal dexamethasone therapy is started at a median gestational age of 6 weeks in a median dose of 20 µg/kg/day. 53% reported maternal adverse events, 8% observed adverse fetal events. Regarding feminizing surgery, 33% reported simultaneous clitoric reduction and vaginoplasty during infancy. However, clitoridectomy is still reported by 13% of centres, and vaginal dilatations have been performed by 27%. Although 71% of female CAH patients with psychosexual problems, only 17% undertake routine psychodiagnostics and counselling. Hydrocortisone is the substance used for the treatment of CAH during growth in 84%; the median dose (mg/m²/day) is 17.5 in infants, 15 in children and adolescents, and 13.75 in adults. The glucocorticoid dose is increased two- to sixfold during intercurrent stress. Mineralocorticoid is administered in cases of clinically manifest salt wasting and of elevated plasma renin activity, to decrease high glucocorticoid doses, or according to genotype. All participating ESPE members feel the need for further improvement in prenatal diagnosis and treatment, compliance during puberty, screening programmes, psychological aspects, and corrective surgery.
Acute Urinary Retention in the Elderly: An Unusual Presentation of Appendicitis with a High Perforation Risk
Authors: Liu Chun-Chu , Yen David H.T. , Lu Ching-Liang , Chern Chii-Hwa , Lee Chen-Hsen
Published: April 2003

Background: Urological manifestations are rare in acute appendicitis. Although acute urinary retention (AUR) is more commonly found in elderly patients, any previous cases reported have been under the age of 30. Objective: The aim of this study was to investigate the incidence, clinical presentation, and results of adult appendicitis patients presenting with AUR. AUR is defined as the sudden inability to urinate with obstructive symptoms. Methods: A retrospective case note review of 480 adult patients (≧18 years) with appendicitis, diagnosed at the Veterans General Hospital-Taipei over a 3-year period, was carried out. Results: Six patients (1.3% of the adults or 3.9% of the elderly patients), 5 men and 1 woman averaging 71.5 years of age, presented with AUR. Associated existing diseases were benign prostatic hyperplasia in 2 of the males and surgical repair for uterine prolapse in the only female. The mean duration from initial gastrointestinal symptoms to AUR was 1.7 days. The quantity of residual urine ranged from 180 to 450 ml. All patients had persistent right lower quadrant tenderness and hematuria. Five (83.3%) were found to have a perforated appendix at operation, and their average hospital stay was 14.7 (8–29) days. Conclusions: AUR may occur as an initial presentation in acute complicated appendicitis in the elderly. It has been reported that the prolonged hospital stay might be related to the delayed diagnosis and resulting complications arising in these patients. Primary care physicians need to be reminded that this common genitourinary complaint may arise in patients with acute appendicitis. When confronted with a geriatric patient presenting with AUR, one should entertain an alternative diagnosis and a reexamination of the patient is mandatory.
Quantitative Vibration Perception Thresholds in Normal and Diabetic Chinese: Influence of Age, Height and Body Mass Index
Authors: Hwu Chii-Min , Chang Hsing-Yi , Chen Jim-Yi , Wang Shu-Li , Ho Low-Tone , Pan Wen-Harn
Published: April 2003

In this study, we established normality data of vibration perception thresholds (VPT) in a Chinese population. Over 1,400 healthy subjects were recruited to create age-related centile charts of VPT after pretesting for reliability. Another 273 diabetic (DM) patients were recruited to assess the impact of age, height and body mass index (BMI) on VPT values in DM and non-DM subjects. The present study is the first one which reports normality data of VPT from a large Chinese population. The VPT values were higher in male and female DM patients than in the non-DM counterparts. Age significantly contributed to the variance of VPT in both DM and non-DM subjects. Height was positively associated with VPT in men, so was BMI in non-DM subjects with much smaller magnitudes of effect than for age.
Penile Arteries and Erection
Authors: Simonsen Ulf , García-Sacristán Albino , Prieto Dolores
Published: April 2003

Alterations in the flow of blood to and from the penis are thought to be the most frequent causes of male erectile dysfunction and, therefore, the present review focuses on the penile vasculature. In the flaccid state, tonic noradrenaline release from the sympathetic nerves contracts penile arterial and corporal smooth muscle through activation of postjunctional α1-adrenoceptors, both by increasing intracellular calcium and by enhancing the sensitivity of the contractile apparatus for calcium. In addition, noradrenaline inhibits vasodilatatory neurotransmitter release by prejunctional α2-adrenoceptors. The exact role of the sympathetic neurotransmitters, neuropeptide Y and adenosine 5′-triphosphate, in erection is largely unknown. Penile vasodilatation during erection is mediated by nitric oxide (NO) through activation of guanylyl cyclase in the smooth muscle layer, followed by increases in cyclic guanosine monophosphate lowering of intracellular calcium and desensitisation of the contractile apparatus for calcium. Acetylcholine, vasoactive intestinal peptide as well as peptides in sensory nerves probably also play a role in penile vasodilation. Increased flow through the penile arteries stimulates the endothelium leading to release of NO, prostanoids and a non-NO non-prostanoid factor, and as such enhances the vasodilatation, while the role of endothelium-derived contractile factors in penile vasoconstriction is not clear. Erectile dysfunction shares arterial risk factors with ischaemic heart disease, and diabetes, age, and hypercholesterolaemia are associated with impairment of both neurogenic and endothelium-dependent vasodilator mechanisms in corpus cavernosum. Only few studies have investigated the impact of these risk factors on the penile vasculature, although recent evidence suggests that arterial insufficiency precedes changes in corpus cavernosum leading to erectile dysfunction.
The Plication Procedure for Penile Curvature: Surgical Outcome and Postoperative Sexual Functioning
Authors: van der Drift D.G.F. , Vroege J.A. , Groenendijk P.M. , Slob A.K. , Schröder F.H. , Mickisch G.H.J.
Published: April 2003

Objective: This study evaluates the patients’ judgement of the surgical outcome of the plication procedure, as described by Schröder and Essed, and the postoperative sexual functioning of patients with congenital curvatures and Peyronie’s disease. Patients and Methods: Of 98 patients treated for penile curvatures between 1985 and 1996, 85 patients received postoperatively a ‘Questionnaire Assessing the Outcome of Surgery’ and a short version of the ‘Questionnaire for Screening Sexual Dysfunctions’. Results: 28 patients with congenital curvatures and 31 with Peyronie’s disease were evaluated. 75% of the patients with congenital curvatures and 58% of the patients with Peyronie’s disease were satisfied with the result. Patients treated for Peyronie’s disease reported diminished penile length and inability to have sexual intercourse more often than patients with congenital curvatures (90 vs. 64%, and 29 vs. 0%). After correction for age, patients with Peyronie’s disease were less satisfied with their present sex life, had more frequent erectile problems and more trouble with considerable sexual desire than a group of 42 controls. For patients with Peyronie’s disease satisfaction with the result was positively correlated with satisfaction with their present sex life and negatively correlated with the frequency of erectile problems. For patients with congenital curvatures satisfaction with the result was negatively correlated with both a postoperative curvature and a repeat operation. Conclusions: Some patients with Peyronie’s disease may not benefit from surgical correction (alone). Because of the occurrence of sexual problems, future evaluation of the role of pre- and postoperative sexological counselling in achieving better results is recommended.
Extraosseous Ewing’s Sarcoma of the Kidney
Authors: Dogra P.N. , Goel Apul , Kumar Rajeev , Das P.K. , Gupta S. Datta
Published: April 2003

Extraosseous Ewing’s sarcoma/primitive neuroectodermal tumor (EES/PNET) of the kidney is an uncommon entity and usually arises from the retroperitoneum and paraspinal region. We report a case of renal EES/PNET and discuss its clinical features, histological findings and management.
The Clinical Importance of Proton Pump Inhibitor Pharmacokinetics
Authors: Yacyshyn B.R. , Thomson A.B.R.
Published: April 2003

Achieving the optimal clinical response for patients with upper gastrointestinal peptic disease is important. This response depends on the pathology treated as well as on the choice of proton pump inhibitor. Here, we identify factors in specific disease therapy and proton pump inhibitor (PPI) pharmacokinetic and pharmacodynamic characteristics that help us achieve this goal. These include differences in PPI bioavailability and acid-suppressive effects. Available data indicate that PPIs appear to have similar potency on a milligram basis, and that omeprazole and lansoprazole are more frequently double dosed than pantoprazole. The lower propensity for double dosing with pantoprazole may also result in lower medication acquisition costs and a reduction in physician visits due to ineffective therapy with the standard dosing of these other agents.
Predicting Postoperative Anterior Chamber Depth in Cataract Patients Using Scheimpflug Slit Photography
Authors: Sasaki Hiroshi , Sakamoto Yasuo , Harada Sachiko , Sakamoto Akiko , Kawakami Yutaka , Nagai Kouta , Takahashi Nobuo , Sasaki Kazuyuki
Published: April 2003

Purpose: To predict the postoperative anterior chamber (AC) depth from the preoperative in situ position of the lens central clear zone (CCZ) using Scheimpflug slit photography. Methods: 111 eyes of 78 cases that underwent phacoemulsification and intraocular lens (IOL) implantation were examined. 748 eyes of 383 healthy subjects with transparent lenses were used as the control. Scheimpflug slit photography was done under maximal mydriasis, and biometry was performed on the photographs. Two types of acrylic IOLs (MA30BA and MA60BM, both from Alcon) were used in this study. The preoperative AC depth (L1), the distance between the anterior lens capsule and lens CCZ (L2) and the postoperative AC depth (I1) were determined. I2, the predicted postoperative AC depth, was then determined from a linear regression of L1 + L2 and I1. Results: L2 thickened by 0.014 mm/year, and L1 decreased by 0.016 mm/year in the transparent lenses. L1 + L2 changed little with aging in both cataractous and transparent lenses. L1 + L2 and I1 showed a linear correlation with r = 0.80 in the MA30BA and r = 0.77 in the MA60BM groups. The mean error values between I1 and I2 were 0.095 ± 0.096 and 0.123 ± 0.114 mm in MA30BA and MA60BM, respectively. The error between I1 and I2 was within ± 0.17 and ± 0.33 mm or less in 72.9 and 91.5% of MA30BA and in 82.7 and 96.2% of MA60BM. In contrast, the error between I2 and I1 when calculated using the SRK/T formula was much larger – in excess of ± 0.33 mm in 38.7% of the eyes. Conclusions: L1 + L2 changes little with aging and is considered a useful marker of the position of the crystalline lens in situ. There was a high correlation between I1 and L1 + L2. These allow a far more accurate prediction of I1 than previous methods. In combination with the conventional regression formula and ray tracing, a highly accurate IOL power calculation can be attained.
Retinal Blood Flow in the Normal Human Eye Using the Canon Laser Blood Flowmeter
Authors: Garcia Jr Julian  P.S. , Garcia Patricia T. , Rosen Richard B.
Published: April 2003

Purpose: To establish a retinal blood flow database in normal human eyes using the Canon Laser Blood Flowmeter (CLBF). Method: Fourteen healthy subjects (7 males, 7 females) between the ages of 24 and 33 underwent birectional laser Doppler velocimetry (BLDV) in one eye using the CLBF. Measurements consisting of blood vessel diameter (D) in micrometers, velocity (V) in millimeters per second, and flow (F) in microliters per minute were recorded at sites along the major retinal veins. Four to six veins were measured in each eye. Total volumetric blood flow was calculated as the sum of the venous flow rates in the major veins. Results: Total retinal blood flow could be reliably determined on 5 of the subjects (1 male, 4 females). Venous blood vessel diameter ranged from 84 to 177 µm. The correlations between D and F, as well as D and V were found to be significant. Specifically, the correlation coefficient between D and F was 0.885 (p ≤ 0.001), while the log-log regression coefficient was 3.35 ± 0.23 (p ≤ 0.001). The correlation coefficient between D and V was 0.694 (p ≤ 0.001), while the log-log regression coefficient was 1.43 ± 0.27 (p ≤ 0.001). Total venous blood flow showed a mean of 64.9 ± (SD) 12.8 µl/min (range: 50.9–80.6 µl/min). Venous blood flow averaged 44.1 ± 4.5 µl/min temporally and 20.8 ± 9.2 µl/min nasally, showing a temporal retinal blood flow approximately twice that of the nasal retina (p < 0.001). On the other hand, venous blood flow averaged 30.6 ± 9.8 µl/min superiorly and 34.3 ± 8.0 µl/min inferiorly. These values showed no statistical difference. Conclusion: The average total retinal blood flow in 5 healthy subjects using the CLBF was 64.9 ± 12.8 µl/min. Venous blood flow at the temporal retina was about twice that of the nasal retina, whereas flow at the superior and inferior retina showed no statistical difference. Our findings are comparable with studies done using a different BLDV system.
Treatment of Chronic Wounds: State of the Art and Future Concepts
Authors: Eming Sabine A. , Smola Hans , Krieg Thomas
Published: April 2003

The morbidity and mortality from chronic wounds of varying etiology present a significant health care problem. Multiple local disturbances and systemic disease can impair wound healing. Recently, experiments with tissue cultures and animal models have revolutionized the understanding of wound healing and the pathophysiological processes involved. In cooperation with clinicians and industrial partners novel therapeutic concepts including the topical application of growth factors and cell therapies have been developed. Cytokines that have been tested in clinical studies include epidermal growth factor, platelet-derived growth factor and fibroblast growth factor. These studies showed that an important aspect of the growth factor wound healing paradigm is the effective delivery of these polypeptides to the wound site. Current drug delivery strategies suffer from the inherent loss of drug activity due to the combined effects of physical inhibition and biological degradation. A molecular genetic approach in which genetically modified cells synthesize and deliver the desired growth factor in a time-regulated manner is a powerful means to overcome the limitations associated with the topical application of recombinant growth factor proteins.
Reaction of Keratinocytes to Exogenous DNA
Authors: Mirmohammadsadegh Alireza , Maschke Jan , Basner-Tschakarjan Etiena , Bär Annett , Hengge Ulrich R.
Published: April 2003

Keratinocytes have the ability to take up oligonucleotides (ODN) and plasmid DNA probably by receptor-mediated endocytosis or macropinocytosis. Despite the use of DNA for antisense and gene therapy, little is known about the regulation of genes following exposure to nucleic acids. To systematically identify gene regulation in keratinocytes upon exposure to ODN, we screened human cytokine DNA arrays containing 383 different genes and found interleukin-1α (IL-1α), IL-1β, integrin β1, α-tubulin and follistatin greatly induced, while most genes were unaffected. The time course and concentration dependence for IL-1α and follistatin was confirmed by the standard Northern blot technique and found to be induced by picomolar or femtomolar concentrations of ODN. ODN of different length and sequence induced comparable amounts of IL-1α and follistatin. Their induction was independent of the negative charge and of several proinflammatory compounds and proteins such as lipopolysaccharides, IL-1β or IFN-γ, but was partly inhibited by activin A. In summary, our study revealed several genes of the acute phase protein family that were induced in a non-sequence-specific manner following the exposure of normal human keratinocytes to ODN. Therefore, it is tempting to speculate that, upon internalization, ODN bind to an intracellular receptor (e.g. Toll-like receptor 9), which mediates signaling.
Intrathecal Bradykinin Administration: Opposite Effects on Nociceptive Transmission
Authors: Sot Urszula , Misterek Krystyna , Witold Gumułka Stanisław , Dorociak Anna
Published: April 2003

Injected intrathecally, bradykinin (BK) produced either hyperalgesia (0.15 µg) or antinociception (6.0 µg) in rats when thermal noxious stimuli were used. Similarly, des-Arg9-BK at the lower dose (0.15 µg) decreased, whereas at the higher dose (6.0 µg) it increased the threshold to thermal noxious stimuli; however, these effects were less pronounced than those of BK. The antinociception induced by BK was abolished by HOE 140, a B2 receptor antagonist, injected intrathecally at a dose of 1.3 ng and was markedly attenuated by des-Arg10-HOE 140, a B1 receptor antagonist (1.15 ng i.t.). The results obtained in this study showed that – depending on the dose used – BK and des-Arg9-BK could produce pro- as well as antinociceptive actions. Both B2 and B1 receptors are involved in the action of intrathecally applied BK.
Paradoxical Pharmacological Effects of Deoxy-Tetrahydrocannabinol Analogs Lacking High CB1 Receptor Affinity
Authors: Wiley Jenny L. , Jefferson Renée G. , Griffin Graeme , Liddle John , Yu Shu , Huffman John W. , Martin Billy R.
Published: April 2003

The present study investigated the role of peripheral cannabinoid (CB2) receptors in producing hypomobility, antinociception and hypothermia in mice. Results revealed that the CB2-selective antagonist, SR144528, did not block cannabimimetic effects of a potent Δ8-tetrahydrocannabinol (THC) analog in mice. While most of a series of CB2-selective 1-deoxy-THC analogs were active in vivo only if they also had good affinity for CB1 receptors, four of these analogs showed in vivo activity even though their affinities for CB1 receptors were poor. Further, this activity was blocked by the CB1 antagonist SR141716A, but not by SR144528. One of the deoxy analogs also stimulated [35S]GTPγS binding, an effect that was blocked by SR141716A. These results provide further evidence that these cannabimimetic effects are not mediated through action at CB2 receptors. In addition, some of these analogs may be very low efficacy agonists at CB1 receptors that act as full agonists in vivo, but lack the ability to displace high affinity and high efficacy binding ligands in vitro.
Effect of SMP-500, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Serum Cholesterol Level and LDL Cholesterol Clearance in Hamsters with Induced Hyperlipidemia
Authors: Ioriya Katsuhisa , Kino Kouichi , Sato Yumi F. , Ohashi Naohito
Published: April 2003

The effect of SMP-500, a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on serum cholesterol levels was investigated in hyperlipidemic hamsters whose condition had been preestablished by diet. SMP-500 reduced the total serum cholesterol level in a dose-dependent manner. SMP-500 also reduced the hepatic free cholesterol content and markedly reduced the esterified cholesterol content compared with the control group. Interestingly, SMP-500 at a dose of 30 mg/kg increased LDL clearance in vivo. As SMP-500 at this dose potently lowered the total serum cholesterol level, the increased LDL clearance was identified as another mechanism for the cholesterol-lowering effect of SMP-500. However, unlike HMG CoA reductase inhibitors, SMP-500 did not affect cholesterol biosynthesis in HepG2 cells. Therefore the etiology of the increased LDL clearance is not yet clear, but the reduced hepatic free cholesterol may play an important role in this process. These results suggest that the cholesterol-lowering effect of SMP-500 is due, not only to the inhibition of ACAT, but also to the increase in cholesterol clearance from the blood. This finding supports the therapeutic potential of SMP-500 for the treatment of human hypercholesterolemia.
Survival of Multiple Sclerosis Patients in the Belgrade Population
Authors: Pekmezovic Tatjana , Jarebinski Mirjana , Drulovic Jelena , Stojsavljevic Nebojsa , Levic Zvonimir
Published: April 2003

The aim of this study was to estimate survival rates of multiple sclerosis (MS) patients in the Belgrade population, Yugoslavia, and furthermore, to determine the prognostic value of some demographic and clinical variables for survival. The cumulative survival probability was calculated by the Kaplan-Meier method. The prognostic value of different variables was assessed by univariate and multivariate analyses using the Cox regression model. In the Belgrade population, the cumulative 25-year survival probability of MS patients and the mean survival time from MS onset were 73.2% and 38 years, respectively. The univariate analysis showed that survival was significantly related to sex, age at onset, course of disease and monoregional initial symptoms. A multivariate model demonstrated that a relapsing-remitting course of MS and monoregional onset were predictors of a better prognosis. The presence of motor symptoms at the onset was found to be an independent predictor of a poorer outcome of MS.
CT Patterns and Long-Term Outcome in Patients with an Aneurysmal Type of Subarachnoid Hemorrhage and Repeatedly Negative Angiograms
Authors: Ruigrok Ynte M. , Rinkel Gabriël J.E. , van Gijn J.
Published: April 2003

The fate of patients with subarachnoid haemorrhage, an aneurysmal pattern of haemorrhage on CT and two or more negative angiographies is unknown. We studied the long-term outcome of patients with three negative angiograms (n = 15) and compared the pattern of hemorrhage of these patients with that of patients with perimesencephalic hemorrhage (n = 73). We reviewed the CT scans of all patients and we followed up the patients with three negative angiograms. The mean period of follow up was 65 months; the number of patient years was 81. In five of the 15 patients with an aneurysmal pattern of hemorrhage the CT scan showed a hemorrhage resembling an anterior circulation aneurysm; in the other 10 patients the center of hemorrhage was behind the chiasm but extended too far in anterior or lateral cisterns to meet the criteria of a true perimesencephalic hemorrhage (‘extended perimesencephalic pattern’). During follow up no episodes of proven aneurysmal rupture had occurred. Three patients subsequently had serious vascular events; one patient (with an extended perimesencephalic pattern) died suddenly; two patients with a pattern of hemorrhage suggestive of an anterior circulation aneurysm were left disabled, one from two episodes of cerebral ischemia and another from a spontaneous intracerbral hemorrhage. In contrast to patients with perimesencephalic hemorrhage who have an uneventful clinical course and an excellent outcome, patients with three negative angiograms and an aneurysmal pattern of hemorrhage are still at some risk of vascular complications and poor outcome. Subdivisions according to the center of hemorrhage once the anterior cisterns are involved is not helpful in identifying patients with good or poor outcome.