bluuebunny/crossref_metadata_2025 huggingface dataset:
24 Response on Epoetin Treatment is Poor in Hemodialysed Patients with Low Creatinine and Albumin Values
Authors: Knap B , Lainščak M , Varl J , Bren AF
Published: February 2005

Background Anemia frequently accompanies chronic renal failure in patients treated with hemodialysis (HD). Despite treatment with erythropoetin up to 10% of patients still present with pronounced anemia. In the present study we wanted to identify simple laboratory parameters or clinical characteristics, associated to anemia in patients treated with erythropoetin.

Methods During May 2003 we screened all patients at our hemodialysis center for the presence of severe anemia (Hemoglobin (Hb) 100 or lower, Group 1) and compared them to the patients without anemia (Hb 120 or higher, Group 2). Patients with chronic bleeding or the ones receiving transfusion were excluded. Basic demographic characteristics, blood pressure, and several biochemical markers were obtained for the enrolled patients. All data were tested for significance using Student's t‐test.

Results Out of 177 patients, 34 (Group 1) and 38 (Group 2) met the inclusion criteria. There was no difference in age, gender, time on HD and blood pressure (148 ± 22/81 ± 13 mm Hg vs. 151 ± 33/81 ± 15 mm Hg). Next to significant difference all hematological parameters (Hb 92 ± 8 vs. 127 ± 6; Ht 0.29 ± 0.03 vs. 0.40 ± 0.02; Ery 3.04 ± 0.32 vs. 4.17 ± 0.32; P < 0.001 for all) patients with anemia received a higher weekly dose of erythropoetin (12000 ± 5205 IE vs. 7825 ± 4829 IE, P < 0.001), had lower albumin (35.6 ± 3.4 vs. 38.1 ± 2.8, P < 0.001) and creatinine concentration (798 ± 218 vs. 932 ± 266, P < 0.005). For other markers such as ferritin, iPTH, folic acid, and vitamin B12 we observed a trend to higher values in anemic patients.

Conclusions Our data suggest that malnutrition and low muscle mass are associated to poor response of treatment with erythropoetin in patients with chronic renal failure treated with HD. Larger sample and prospective follow up could identify further simple markers of inadequate response to the treatment of anemia.
27 Citrate Anticoagulation for Single‐Needle Hemodialysis: Safety and Efficacy
Authors: Buturović‐Ponikvar J , Gubenšek J , Ponikvar R
Published: February 2005

Background  Single‐needle (SN) hemodialysis can be the only option for selected patients with difficulties with vascular access. Full heparinization is required to avoid clotting in the circuit. In patients at risk of bleeding, citrate could be the alternative anticoagulant. The aim of our retrospective clinical study was to evaluate safety and efficacy of regional citrate anticoagulation (RCA) during SN hemodialysis.

Patients and methods  Regional citrate anticoagulation was performed using 4% trisodium citrate, 1 m CaCl2 and dialysate with 0 mmol/L Ca, 0.5 mmol/L Mg and 0 g/L glucose, Na was set at 138 mmol/L and HCO3 at 28 mmol/L. Safety was assessed by percent of procedures that were terminated prematurely or changed to another modality due to RCA‐related complications and by incidence of important hypocalcemia, defined as decrease of iCa from start of dialysis > 0.2 mmol/L or decrease > 0.05 mmol/L to a value of < 0.8 mmol/L. Efficacy was evaluated by visual assessing of clot formation in arterial and venous bubble traps and dialyzer, after completing dialysis, by scoring: grade 5 (<10 fibers clotted) to 0 (>20% fibers clotted). It was considered insufficient if the grade was ≤ 3 or a significant clot in bubble traps occurred.

Results  In retrospective analysis of 41 protocols, important hypocalcemia was recorded in 34% of cases. 5% of procedures were terminated prematurely. Median dialyzer grade was 5 (interquartile range 4–5, N = 36). Anticoagulation was insufficient in 17% (6/36) of procedures, in these cases neither citrate infusion rate was lower nor coagulation time shorter. None of the systems clotted. Thirty protocols were filled in completely; average parameters are shown in the table below. In the first hour iCa decreased in 67% of procedures for 0.08 ± 0.05 mmol/L, those procedures had significantly lower starting calcium rate (6.4 ± 0.9 vs. 7.3 ± 1.1 mmol/L, P = 0.02) and higher starting iCa (1.02 ± 0.13 vs. 0.89 ± 0.14 mmol/L, P = 0.02). Over the entire procedure iCa decreased in 80% of cases for 0.17 ± 0.09 mmol/L, there was significant but small increase in Na (135 ± 4 vs. 137 ± 4 mmol/L, P ≤ 0.01) and no increase in HCO3 at the end of hemodialysis (Table A27).

Parameter
Value

blood flow (mL/min)
244 ± 27

starting rate of 4% Na citrate (mL/h)
191 ± 19

citrate rate (percent of mean blood flow)
2.6% ± 0.4%

starting rate of 1 m CaCl2 (mL/h)
6.7 ± 1.1

Conclusions  Citrate anticoagulation during single‐needle hemodialysis is a safe and effective procedure in the majority of patients. CaCl2 infusion rate should often be increased to correct hypocalcemia. Close monitoring of iCa is mandatory. Increased starting dose of CaCl2 should be evaluated.
36 Prevention of Early Acute Rejection with Basiliximab and Triple Immunosuppression in Cadaveric Renal Allograft Recipients
Authors: Kandus A , Grego K , Arnol M , Kovač D , Kovač J , Lindič J , Buturović‐Ponikvar J , Ponikvar R , Bren A F
Published: February 2005

We assessed the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of at least 1 HLA‐mismatched cadaveric renal allograft. All studied patients, transplanted between October 1999 and December 2003, received equal immunosuppression: 20 mg infusion of basiliximab on day 0 and on day 4, infusion of cyclosporine (CyA) (0.08 mg/kg/h) started at operation and continued by CyA‐Neoral, 3 mg/kg b.i.d. on day 2, methylprednisolone, 0.4 mg/kg i.v. at operation, and mycophenolate mofetil started on day 1. CyA‐Neoral dose was adjusted to maintain blood trough levels of 150–250 ng/mL (FPIA, monoclonal). Oral methylprednisolone was tapered by 4 mg per week to achieve a maintenance dose of 0.08 mg/kg/day. A total of 153 patients, with mean age of 46 ± 11 years (SD; range 18–65 years), were studied. Thirteen of them received second renal allograft. The mean donor age was 37 ± 14 years (range 6–61 years). Mean cold ischemia time was 22.0 ± 8.0 h (range 7.0–41.0 h), mean value of HLA‐antigen mismatches was 3.0 ± 0.9 (range 1–5), mean latest PRA value was 8 ± 14% (range 0–85%). 47 patients experienced delayed graft function. During a follow‐up of 3 months no acute rejection episode occurred. Four renal allografts were removed, but not for rejection. One patient died because of sepsis. In one patient life‐threatening CMV disease was successfully treated. One malignancy (skin basal cell carcinoma) was detected. Hypersensitivity reactions and cytokine‐release syndrome were not observed. After 3 months mean serum creatinine was 111 ± 36 µmol/L (range 53–238 µmol/L). Patient and graft survival was 99.3% and 97.4%, respectively. We conclude that basiliximab with this triple therapy is an efficient and safe immunosuppression strategy, demonstrated with absence of early acute rejection episodes, excellent allograft function, acceptable adverse event profile and high short‐term survival rate.
37 Prevention of Early Acute Rejection with Daclizumab and Triple Immunosuppression in Cadaveric Renal Allograft Recipients
Authors: Kandus A , Grego K , Arnol M , Kovač D , Kovač J , Lindič J , Bren A F
Published: February 2005

We assessed the safety and efficacy of daclizumab combined with triple immunosuppression in adult recipients of at least 1 HLA‐mismatched cadaveric renal allograft. All studied patients received equal immunosuppression: daclizumab infusion of 1 mg/kg immediately before transplantation and at 2, 4, 6 and 8 weeks following the transplantation, infusion of cyclosporine (CyA) (0.08 mg/kg/hr) started at operation and continued by CyA‐Neoral, 3 mg/kg b.i.d. on day 2, methylprednisolone, 0.4 mg/kg i.v. at operation, and mycophenolate mofetil started on day 1. CyA‐Neoral dose was adjusted to maintain blood trough levels of 100–170 ng/mL (FPIA, monoclonal). Oral methylprednisolone was tapered by 4 mg per week to achieve maintenance dose of 0.08 mg/kg/day. 39 patients, with mean age of 49 ± 10 years (SD; range 26–66 years), were studied. Three of them received a second renal allograft. The mean donor age was 38 ± 13 years (range 16–58 years). Mean cold ischemia time was 19.0 ± 6.5 h (range 9.5–39.5 h), mean value of HLA‐antigen mismatches was 2.7 ± 1.0 (range 1–5), mean latest PRA value was 3 ± 8% (range 0–47%). Ten patients experienced delayed graft function. During follow‐up of 3 months one acute rejection episode was observed, vascular type, treated with OKT3. One patient experienced a hypersensitivity reaction to daclizumab, which despite precautionary measures required early interruption of the 5th infusion dose. In two patients CMV disease, requiring hospitalisation, was successfully treated. No malignancies were detected. After 3 months mean serum creatinine was 102.2 ± 24.0 µmol/L (range 63–152 µmol/L). 2 renal allografts were removed, but not for rejection. Patient and graft survival was 100% and 94.9%, respectively. We conclude that daclizumab with this triple therapy represents a safe and efficient immunosuppression strategy, demonstrated with low incidence of early acute rejection episodes, excellent allograft function, acceptable adverse event profile and high short‐term survival rate.
39 De Novo Malignancies After Renal Transplantation – A Single Center Experience
Authors: Ivanovski N , Popov Z , Kolevski P , Čakalaroski K , Masin J , Zafirovska K
Published: February 2005

Background  The occurrence of malignancies after organ transplantation is a well known and very serious complication. According to many authors, the overall prevalence of malignancies after renal transplantation is between 6 and 12%. Despite the fact that many factors could be involved, the etiopathogenesis is still unclear. The aim of the authors is to present their own clinical experience in early diagnosis and treatment of de novo malignancies after renal transplantation.

Patients and Methods  Over a period of 12 years, 184 renal transplant (138 living related and 46 cadaveric) were performed and followed in our department on an outpatient basis. All patients were treated by sequential quadruple immunosuppressive protocol with mono (Il‐2R antagonists) and polyclonal antibody (ATG) induction therapy and Cyclosporine A, Mycophenolate Mofetil or/and Azathioprine, and Prednisolone as maintenance therapy. The standard surgical and preservation procedure was performed in most of the patients. The mean cold ischemia time in living renal transplants was 3.6 h, while in cadaver was 25.6 h. About 20% of the patients developed acute rejection episodes, successfully treated by steroid pulse therapy. According to the protocol in the Department the patients were regularly examined once‐monthly during the whole period of follow up.

Results  Overall 18 malignancies (9.78%) in 14 patients (7.8%) were observed. All cases were clinically and histologically confirmed. Of 14 transplant patients with malignancies, 4 were female and 10 male. The mean age of patients with cancer was 45 years (range 21–53). Most of the malignancies were basal and/or squamous skin cancers (10 or 55%). Kaposi's sarcomas were found in 3 patients (16.6%, one visceral form). One breast cancer, one seminoma, one cancer of the colon, one urogenital cancer in female, one renal cell carcinoma and one plasmocytoma, were detected to. Surprisingly no cases of post‐transplant lymphoproliferative disease (PTLD) were observed. All cancers were de novo malignancies presented in a mean time of 21 months (range 2–52 months) after surgery. The overall mortality rate was 42.6%, most among the patients with solid organ cancers. Three grafts were lost because of reduction and cessation of immunosuppression in patients with visceral form of Kaposi's sarcoma, multiple skin cancers and plasmocytoma. We did not observe any correlation between the clinical occurrence of post‐transplant malignancies and different HLA type, number of rejection episodes as well as any specific bacterial, viral, or fungal infection.

Conclusion  The prevalence of post‐transplant malignancies in our group of patients is similar to other authors. The predominance of the skin cancers is understandable bearing in mind the sunny side of the country. Careful clinical examination and long‐term screening protocols are needed for early detection and treatment of this mostly life threatening complication among the transplant population.
Dimensional Accuracy of 7 Die Materials
Authors: Kenyon Brian J. , Hagge Mark S. , Leknius Casimir , Daniels Walter C. , Weed Scott T.
Published: February 2005

Purpose: The purpose of this study was to compare the linear dimensional accuracy and the handling characteristics of 7 die materials.

Materials and Methods: A master die analogous to a complete veneer crown preparation was machined from medical grade stainless steel, and 3 measurements (1: vertical; 2 and 3: horizontal) were made from 3 scribed reference lines. Individual polyvinylsiloxane impressions were made (n = 10) for each of the specimens. The fabricated dies were measured (50×) to the nearest 0.0001 mm. Data were subject to ANOVA/Duncan tests at significance level 0.05 and pairwise comparisons.

Results: Type IV resin‐impregnated dental stone and copper‐plated dies most closely approximated the dimensions of the master die, and were not significantly different from each other in any of the pairwise comparisons. Conventional Types IV and V dental stone dies exhibited setting expansion within the range appropriate for gypsum. Epoxy resin die materials demonstrated shrinkage comparable to the expansion of the Types IV and V dies. Polyurethane dies displayed a combination of linear expansion and shrinkage. Bis‐acryl composite resin dies had excessive shrinkage.

Conclusions: Type IV resin‐impregnated dental stone and copper‐plated dies were more dimensionally accurate than the other die materials tested.
Periodontitis lesions are a source of salivary cytomegalovirus and Epstein–Barr virus
Authors: Saygun Işıl , Kubar Ayhan , Özdemir Atilla , Slots Jørgen
Published: February 2005

Aim:  Several herpesvirus species can be detected in periodontal pockets and saliva. This study compared human cytomegalovirus (HCMV) and Epstein–Barr virus (EBV) DNA copy counts in periodontitis sites and in whole saliva, and evaluated the potential of periodontal therapy to reduce the salivary level of the two viruses.

Material and methods:  A total of 20 systemically healthy periodontitis patients, 21–56 years of age, participated in the study. All 20 patients were examined at baseline, and seven patients also at 3 months after periodontal therapy. Treatment included oral hygiene instruction, scaling and root planing, and surgery. Clinical parameters were evaluated using established methods. In each patient, virological samples were collected from one periodontal pocket of 6–10 mm probing depth, from the adjacent inflamed periodontal pocket wall, and from unstimulated whole saliva. Relationships between subgingival, gingival tissue and salivary herpesvirus counts were evaluated using Spearman's and Kendall's rank correlation coefficient tests. The 5′‐nuclease (TaqMan®) real‐time polymerase chain reaction (PCR) assay was employed to quantify genomic copies of periodontal HCMV and EBV.

Results:  At baseline, the 20 periodontitis patients showed significant positive correlations between gingival tissue and salivary counts of HCMV DNA (p = 0.003) and EBV DNA (p = 0.045). Periodontal pocket depth was positively correlated with salivary EBV DNA counts (p = 0.002). Periodontal therapy reduced average full‐mouth periodontal pocket depth from 4.6 mm to 1.4 mm, plaque index from 2.1 to 0.9, and gingival index from 2.1 to 0.4. Following treatment, HCMV DNA counts decreased 37.5 fold in subgingival sites and 64.6 fold in saliva, and EBV DNA counts decreased 5.7 fold in subgingival sites and 12.9 fold in saliva.

Conclusions:  The present study provides compelling evidence of a periodontitis source for salivary HCMV and EBV. The potential of periodontal therapy to decrease herpesvirus salivary counts may help diminish herpesvirus transmission from person to person and herpesvirus‐related diseases in exposed individuals. Further research is warranted to determine the relationship between periodontal herpesvirus counts and the risk of viral transmission to close acquaintances.
RELATIONSHIP BETWEEN ANTHOCYANIN PATTERNS AND ANTIOXIDANT CAPACITY IN MULBERRY WINE DURING STORAGE
Authors: TSAI PI‐JEN , HUANG HSIAO‐PING , HUANG TZOU‐CHI
Published: February 2005

Mulberry wine stored for 1, 3, and 12 months was used to investigate the relationship between wine color, copigmentation, polymerization of anthocyanins, and the antioxidant capacity of the wine. Color density, patterns of anthocyanins (monomeric, copigmented and polymeric) and antioxidant capacity were measured. The results show that copigmented and polymeric anthocyanins in mulberry wine increased from 0% and 16.63% to 20.93% and 30.44%, respectively, while monomeric anthocyanins decreased from 83.37% to 48.63%. The 1,1,Diphenyl‐2‐picryl‐hydrazyl (DPPH) radical scavenging ability increased after storage and was highly correlated with the polymeric anthocyanin content (r = 0.98). The ferric reducing ability of plasma (FRAP) reducing power decreased on storage. Sephadex G25 was used to separate the pigments into three different molecular sizes. The largest molecules were in Fraction I, which contained the polymerized anthocyanins and was associated with the DPPH scavenging activity. Fraction II, intermediate in size, contained the copigmented anthocyanins. Fraction III, the smallest in size, was composed of the monomeric anthocyanins and was associated with the FRAP activity.
PHYSICOCHEMICAL CHARACTERISTICS AND SENSORY ATTRIBUTES OF WHEAT‐BASED “PAPADS” INCORPORATED WITH GREEN LEAFY VEGETABLES
Authors: KAVERI GUNALAN VASANTHI , GUPTA SHEETAL , LAKSHMI A. JYOTHI , PRAKASH JAMUNA
Published: February 2005

Papads are cereal or legume‐based preserved products which are consumed after deep fat frying. They were chosen for value addition with two types of green leafy vegetables (GLV). Wheat‐based papads were prepared using refined wheat flour, cumin seeds, salt and GLV, that is, shepu (Peucedanum graveolens) and kilkeerae (Amaranthus tricolor) at different levels in fresh (15 and 20%) and dehydrated forms (5 and 10%). Greens were analyzed for their proximate principles, selected minerals and vitamins. In the fried papads, fat uptake and expansion volume were determined. The fried papads were subjected to sensory analysis by a panel of 100 members. Expansion volume of papads with fresh greens and 5% dehydrated greens were satisfactory, but differences existed between the greens. Fat uptake of kilkeerae papads was similar to that of control papads but shepu‐incorporated papad showed slightly lower absorption. Papads with 15–20% fresh greens and 5% dehydrated greens scored above 6 on a scale of 10 indicating acceptability of papads incorporated with greens. Mineral, vitamin and fiber content of greens‐incorporated papads increased remarkably. Acceptability of papads in terms of physicochemical characteristics, sensory attributes and nutritional quality suggests the suitability of papads incorporated with greens.
Making Capitalism Work for Everyone
Authors: Rajan Raghuram G. , Zingales Luigi
Published: February 2005

Capitalism–or, more precisely, the free enterprise system–is the most effective system for allocating resources and rewards. For this reason, most economists tend to believe that capitalism is bound to spread from the U.S. to all parts of the world. But the authors argue that the triumph of capitalism is far from certain. Part of the problem is that the forms of capitalism that are experienced in most countries are very far from the ideal. They are a corrupt version in which vested interests prevent competition from playing its socially bene. cial role.

What's more, as many economists fail to recognize, and as has become clear from the experience of many countries in recent years, a market system cannot. ourish without the very visible hand of the government, which is needed to set up and maintain the infrastructure that enables participants to trade freely and with con. dence. But this in turn gives rise to a political, or collective action, problem: Even though we all bene. t from the better goods and services and the equality of access that competitive markets make possible, no one in particular makes huge pro. ts from keeping the system competitive and the playing. eld level; everyone has an incentive to take a free ride and let someone else defend the system. In this sense, a competitive market is a form of public good, one in need of collective action to maintain it.

In all nations, the main political threat to free markets comes from two very different groups: (1) “incumbents,” who want to retain their positions and thus have a strong incentive to suppress any potential source of competition; and (2) those who have lost out and would be happy if the rules of the game that caused their troubles were changed. The longterm feasibility of free markets depends on reducing the incentives and limiting the ability of both of these groups to work against the market. This can be accomplished not by expanding the power of the state, but through policies –including a strengthening of the “safety net” as well as removal of barriers to the. ow of trade and capital–that end up limiting the state's ability to take inef. cient economic actions that favor the few at the expense of the majority.
LDL‐Apheresis Accelerates the Recovery of Nonarteritic Acute Anterior Ischemic Optic Neuropathy
Authors: Ramunni Alfonso , Giancipoli Giovanni , Guerriero Silvana , Lapenna Lucia , Saracino Angelo , Saliani Maria Teresa , Capurso Antonio , Sborgia Carlo , Coratelli Pasquale
Published: February 2005

Abstract: Nonarteritic acute anterior ischemic optic neuropathy (NAION) is a disabling disease which impairs visual function. It is presumed to result from disturbances of microcirculation in the anterior portion of the optic nerve head due to hemodynamic factors derived from excessive blood viscosity, or restriction of the vasal lumen in hypertensive, hypercholesterolemic, diabetic patients. We aimed to determine whether acute reduction of plasma fibrinogen and serum low‐density lipoprotein (LDL) cholesterol is effective for treatment of NAION. We recruited 11 patients (7 females, 4 males) with a mean age of 57.2 ± 19.6 years. All except one of them presented risk factors for atherosclerosis. The mean values of LDL‐cholesterol and fibrinogen before treatment were 144 ± 32 mg/dL and 341 ± 80 mg/dL, respectively. All were treated with standard therapy (prednisone, salicylate, pentoxiphyllin) and underwent three sessions of LDL‐apheresis (HELP system—B Braun) that can reduce plasma LDL‐cholesterol and fibrinogen by more than 50% in a very short time. In all patients we observed a drastic reduction of LDL cholesterol and fibrinogen and a clear improvement in the visual functional data. In fact, mean values of corrected vision increased from 3.7/10 ± 3/10 to 7.9/10 ± 2.2/10 (P = 0.002) after the third session, while the scotomatous portion of the visual field regressed after the first session, and in 5 patients further regressed after the third session. This improvement had remained stable after 3 months. Thanks to it's effect of antagonizing hemorheologic disorders of the ocular microcirculation, fibrinogen/LDL‐apheresis seems to be an efficacious treatment of NAION.
Different Routes Bridging Calcium in Japanese Hemodialysis Patients
Authors: Hamano Takayuki , Fujii Naohiko , Ito Takahito , Imai Enyu
Published: February 2005

Abstract:  There is growing evidence that not only serum calcium concentration but also excess calcium load is associated with vascular calcification and mortality in hemodialysis patients. Calcium load in hemodialysis patients cumulatively comes from three different routes: oral intake of calcium including calcium‐based phosphate binders, traffic of calcium from/to dialysate, and calcemic action of vitamin D. The K/DOQI guidelines recommend sevelamer hydrochloride instead of calcium‐containing phosphate binders to control serum phosphate concentration. However, in Japan, both kinds of phosphate binders are used concomitantly, mainly because Japanese patients are prone to a higher incidence of sevelamer‐associated adverse events such as gastrointestinal symptoms. Regarding the calcium concentration of dialysate (D‐Ca) in Japan, 3.0 mEq/L is more popular than 2.5 mEq/L. Calcium loaded through 3.0 mEq/L dialysate may lead to metastatic calcification rather than to bone formation because serum phosphate concentration rebounds several hours after the end of each hemodialysis session when plasma pH is still high. In contrast, use of 2.5 mEq/L dialysate may result in an unfavorable increase of intact parathyroid hormone particularly when the amount of oral calcium intake is reduced. Although a higher dose of vitamin D is required to counteract the stimulation of parathyroid glands, hypercalcemia is less likely with 2.5 mEq/L dialysate. As the new K/DOQI guidelines are released, it is time to discuss the appropriate D‐Ca as well as doses and kinds of phosphate binders and vitamin D for the comprehensive management of  Japanese  hemodialysis  patients.
Prevention of Limb Amputation in Patients with Limbs Ulcers by Autologous Peripheral Blood Mononuclear Cell Implantation
Authors: Kawamura Akio , Horie Takashi , Tsuda Ichirou , Ikeda Atushi , Egawa Hirotoshi , Imamura Emi , Iida Jun‐ichi , Sakata Hiromi , Tamaki Tohru , Kukita Kazutaka , Meguro Jun‐ichi , Yonekawa Motoki , Kasai Masaharu
Published: February 2005

Abstract:  There are many cases of amputation of ischemic limbs of dialysis patients due to diabetes, despite the availability of medicine therapy and vascular by‐pass operations. As there is extensive ruin of the vascular bed due to diabetes, vascular regeneration therapy by stem cell implantation is effective. Thirty patients with ischemic limbs due to diabetes (not including type‐I) and on dialysis for chronic renal failure (19 cases), diabetes (5 cases), dialysis patients without diabetes (4 cases), and arteriosclerosis obliterans (ASO, 2 cases) were treated by autologous peripheral blood stem cell (PBSC) implantation where imminent amputation was under consideration. Granulocyte Colony Stimulate Factor (G‐CSF: 5 µg/kg/day) was administered subcutaneously for 4 days before PBSC collection, that was carried out using a centrifuge (Spectra and/or CS3000) via the vein. The collected PBSC, containing 4.2 × 107 of CD 34 positive cells, was divided into units of 0.5–1.0 mL and implanted, without any purification, to the ischemic area of the limbs in about 65 points. In 21 cases, normalization of limb temperature was observed by thermograph, and symptoms also improved. The result of this first attempt of PBSC implantation is that we were able to save 22 ischemic limbs. This is the first large report of the application of regenerative medicine to peripheral ischemic limbs.
Modified Virulence of Antibiotic-Induced
Burkholderia pseudomallei
Filaments
Authors: Chen Kang , Sun Guang Wen , Chua Kim Lee , Gan Yunn-Hwen
Published: February 2005

Melioidosis is a life-threatening bacterial infection caused by
Burkholderia pseudomallei
. Some antibiotics used to treat melioidosis can induce filamentation in
B. pseudomallei
. Despite studies on the mechanism of virulence of the bacteria, the properties of
B. pseudomallei
filaments and their impact on virulence have not been investigated before. To understand the characteristics of antibiotic-induced filaments, we performed in vitro assays to compare several aspects of virulence between normal, nonfilamentous and filamentous
B. pseudomallei
. Normal, nonfilamentous
B. pseudomallei
could cause the lysis of monocytic cells, while filaments induced by sublethal concentrations of ceftazidime, ofloxacin, or trimethoprim show decreased lysis of monocytic cells, especially after prolonged antibiotic exposure. The motility of the filamentous bacteria was reduced compared to that of nonfilamentous bacteria. However, the filamentation was reversible when the antibiotics were removed, and the revertant bacteria recovered their motility and ability to lyse monocytic cells. Meanwhile, antibiotic resistance developed in revertant bacteria exposed to ceftazidime at the MIC. Our study highlights the danger of letting antibiotic concentration drop to the MIC or sub-MICs during antibiotic treatment of melioidosis. This could potentially give rise to a temporary reduction of bacterial virulence, only to result in bacteria that are equally virulent but more resistant to antibiotics, should the antibiotics be reduced or removed.
Orally Active Antiviral Tripeptide Glycyl-Prolyl-Glycinamide Is Activated by CD26 (Dipeptidyl Peptidase IV) before Transport across the Intestinal Epithelium
Authors: Hubatsch Ina , Lazorova Lucia , Vahlne Anders , Artursson Per
Published: February 2005

The tripeptide amide glycyl-prolyl-glycinamide (GPG-amide) is a new antiretroviral drug candidate, but its absorption mechanism is unknown. In this investigation, the transport and metabolism of GPG-amide were studied in a model of the human intestinal epithelium, Caco-2 cell monolayers. The results show that when the tripeptide amide came into contact with the apical enterocyte membrane, it was degraded by CD26 (dipeptidyl peptidase IV) to glycylproline and the antiretrovirally active metabolite glycinamide. Glycinamide retained antiretroviral activity in vitro after transport through the Caco-2 cell monolayers. The transport of glycinamide across Caco-2 cell monolayers occurred via passive diffusion with an apparent permeability coefficient of about 2 × 10
−6
cm s
−1
, which suggests that it is absorbed by the oral route in sufficient amounts to be considered for oral administration. In conclusion, the tripeptide GPG-amide acts as a prodrug that is activated by CD26 to release the orally active antiretroviral compound glycinamide.
Pharmacokinetics of Gatifloxacin in Infants and Children
Authors: Capparelli Edmund V. , Reed Michael D. , Bradley John S. , Kearns Gregory L. , Jacobs Richard F. , Damle Bharat D. , Blumer Jeffrey L. , Grasela Dennis M.
Published: February 2005

Gatifloxacin is an 8-methoxy fluoroquinolone effective against a broad spectrum of pathogens common in pediatric infections. The safety and pharmacokinetics of a single dose of gatifloxacin were studied in pediatric patients from 6 months to 16 years of age. Seventy-six pediatric patients (average age, 6.7 ± 5.0 years) were administered a single oral dose of gatifloxacin suspension (5, 10, or 15 mg/kg of body weight; 600-mg maximum) in a dose-escalating manner. Subjects were stratified by age into 4 groups. An additional 12 children, greater than 6 years of age, received gatifloxacin as the tablet formulation at a dose of approximately 10 mg/kg. Gatifloxacin's apparent clearance and half-life were 5.5 ± 2.1 ml/min/kg and 5.1 ± 1.4 h. The maximum concentration of drug in plasma and area under the concentration-time curve (AUC) increased in a manner approximately proportional to the dose. At the 10-mg/kg dose, the bioavailability was similar between the suspension and tablet formulation. The apparent oral clearance of gatifloxacin, normalized for body weight, exhibited a small but statistically significant decrease with increasing age. In all subjects receiving gatifloxacin at 10 mg/kg, the AUC exceeded 20 μg · h/ml (estimated free AUC/MIC ratio of ≥34 for MIC of ≤0.5 μg/ml). These data suggest that gatifloxacin at a dose of 10 mg/kg every 24 h will achieve therapeutic concentrations in plasma in infants and children.
Rifampin-Resistant RNA Polymerase Mutants of
Chlamydia trachomatis
Remain Susceptible to the Ansamycin Rifalazil
Authors: Suchland Robert J. , Bourillon Agnès , Denamur Erick , Stamm Walter E. , Rothstein David M.
Published: February 2005

Stable, homotypic mutants of
Chlamydia trachomatis
for which MICs of rifampin and rifalazil are elevated were isolated by serial passage at sub-MIC concentrations of these compounds. An alternative approach, in which
Chlamydia
cells were incubated and subsequently passaged three times, all in the presence of the selective agent at concentrations above the MIC, appeared to be a more effective means of selecting for mutants. In every instance where an elevation in the MIC occurred, one or more mutations in the
rpoB
gene, encoding the rifampin binding site, were detected. With one exception, all
rpoB
mutants that contained a single mutation conferred lower levels of resistance than mutants containing multiple mutations. Some
rpoB
mutations conferred very high levels of resistance to rifampin, up to 512 μg/ml. In all cases, mutants remained susceptible to concentrations of rifalazil at or below 0.064 μg/ml. Thus, rifalazil, a compound that is extremely potent against
Chlamydia
wild-type cells (MIC of 0.00025 μg/ml), may also protect against the selection of mutants at physiologically achievable concentrations.
In Vitro Activity of Structurally Diverse Nucleoside Analogs against Human Immunodeficiency Virus Type 1 with the K65R Mutation in Reverse Transcriptase
Authors: Parikh Urvi M. , Koontz Dianna L. , Chu Chung K. , Schinazi Raymond F. , Mellors John W.
Published: February 2005

Human immunodeficiency virus type 1 (HIV-1) with a lysine-to-arginine substitution at codon 65 (HIV-165R) of reverse transcriptase (RT) can rapidly emerge in patients being treated with specific combinations of nucleoside analog RT inhibitors (NRTIs). A better understanding of the activity of approved and investigational NRTIs against HIV-165Ris needed to select optimal therapy for patients infected with this mutant and to devise strategies to prevent its emergence. Therefore, we tested a broad panel of NRTIs that differed by enantiomer, pseudosugar, and base component against HIV-165Rto determine how NRTI structure affects activity. Drug susceptibilities of recombinant wild-type (HIV-165K) or mutant HIV-165Rwere determined using a single-replication-cycle susceptibility assay with P4/R5 cells and/or a multiple-replication-cycle susceptibility assay with MT-2 cells. Alld,l, and acyclic NRTIs were significantly less active against HIV-165Rthan against HIV-165Kexcept for analogs containing a 3′-azido moiety. Pseudosugar structure and base component but not enantiomer influenced NRTI activity against HIV-165R. These findings support the inclusion of 3′-azido-3′-deoxythymidine in drug combinations to treat patients having HIV-165Rand to prevent its emergence.
Antimalarial Activities and Therapeutic Properties of Febrifugine Analogs
Authors: Jiang Suping , Zeng Qiang , Gettayacamin Montip , Tungtaeng Anchalee , Wannaying Srisombat , Lim Apassorn , Hansukjariya Pranee , Okunji Christopher O. , Zhu Shuren , Fang Daohe
Published: February 2005

Febrifugine is the active principal isolated 50 years ago from the Chinese herb chang shan (
Dichroa febrifuga
Lour), which has been used as an antimalarial in Chinese traditional medicine for more than 2,000 years. However, intensive study of the properties of febrifugine has been hindered for decades due to its side effects. We report new findings on the effects of febrifugine analogs compared with those of febrifugine extracted from the dry roots of
D. febrifuga
. The properties of the extracted febrifugine were comparable to those obtained from the standard febrifugine provided by our collaborators. A febrifugine structure-based computer search of the Walter Reed Chemical Information System identified 10 analogs that inhibited parasite growth in vitro, with 50% inhibitory concentrations ranging from 0.141 to 290 ng/ml. The host macrophages (J744 cells) were 50 to 100 times less sensitive to the febrifugine analogs than the parasites. Neuronal (NG108) cells were even more insensitive to these drugs (selectivity indices, >1,000), indicating that a feasible therapeutic index for humans could be established. The analogs, particularly halofuginone, notably reduced parasitemias to undetectable levels and displayed curative effects in
Plasmodium berghei
-infected mice. Recrudescence of the parasites after treatment with the febrifugine analogs was the key factor that caused the death of most of the mice in groups receiving an effective dose. Subcutaneous treatments with the analogs did not cause irritation of the gastrointestinal tract when the animals were treated with doses within the antimalarial dose range. In summary, these analogs appear to be promising lead antimalarial compounds that require intensive study for optimization for further down-selection and development.
Activity of Cathelicidin Peptides against
Chlamydia
spp
Authors: Donati Manuela , Di Leo Korinne , Benincasa Monica , Cavrini Francesca , Accardo Silvia , Moroni Alessandra , Gennaro Renato , Cevenini Roberto
Published: February 2005

The in vitro activity of six cathelicidin peptides against 25 strains of
Chlamydia
was investigated. SMAP-29 proved to be the most active peptide, reducing the inclusion numbers of all 10 strains of
Chlamydia trachomatis
tested by ≥50% at 10 μg/ml. This peptide was also active against
C. pneumoniae
and
C. felis.
Experimental Bacteriophage Protection against
Staphylococcus aureus
Abscesses in a Rabbit Model
Authors: Wills Quintin F. , Kerrigan Claire , Soothill James S.
Published: February 2005

In a rabbit model of wound infection caused by
Staphylococcus aureus
, 2 × 10
9
PFU of staphylococcal phage prevented abscess formation in rabbits when it was injected simultaneously with
S
.
aureus
(8 × 10
7
CFU) into the same subcutaneous site. Phage multiplied in the tissues. Phages might be a valuable prophylaxis against staphylococcal infection.
Combined Activity In Vitro of Caspofungin, Amphotericin B, and Azole Agents against Itraconazole-Resistant Clinical Isolates of
Aspergillus fumigatus
Authors: Cuenca-Estrella Manuel , Gomez-Lopez Alicia , Garcia-Effron Guillermo , Alcazar-Fuoli Laura , Mellado Emilia , Buitrago Maria J. , Rodriguez-Tudela Juan L.
Published: February 2005

Interactions in vitro between amphotericin B, itraconazole, voriconazole, and caspofungin against itraconazole-resistant
Aspergillus fumigatus
clinical strains were determined. Differential results were obtained depending on the criteria (MIC or minimal effective concentration) used. Caspofungin and voriconazole exhibited the most potent interactions, with synergy against at least 50% of isolates, and the average fractional concentration index was 0.38. Antagonism was not found for any combination.
In Vitro Activity of the Histatin Derivative P-113 against Multidrug-Resistant Pathogens Responsible for Pneumonia in Immunocompromised Patients
Authors: Giacometti Andrea , Cirioni Oscar , Kamysz Wojciech , D'Amato Giuseppina , Silvestri Carmela , Prete Maria Simona Del , Licci Alberto , Riva Alessandra , Łukasiak Jerzy , Scalise Giorgio
Published: February 2005

The in vitro activity of the histatin derivative P-113, alone or combined with eight antibiotics, was investigated against multidrug-resistant strains isolated from clinical specimens of immunocompromised patients with pneumonia. The gram-negative isolates were susceptible to P-113.
S. aureus
showed less susceptibility. Synergy was demonstrated when P-113 was combined with beta-lactams against gram-negative organisms.
Emergence of Resistance to Rifampin and Rifalazil in
Chlamydophila pneumoniae
and
Chlamydia trachomatis
Authors: Kutlin Andrei , Kohlhoff Stephan , Roblin Patricia , Hammerschlag Margaret R. , Riska Paul
Published: February 2005

Although rifamycins have excellent activity against
Chlamydophila pneumoniae
and
Chlamydia trachomatis
in vitro, concerns about the possible development of resistance during therapy have discouraged their use for treatment of chlamydial infections. Rifalazil, a new semisynthetic rifamycin with a long half-life, is the most active antimicrobial against
C. pneumoniae
and
C. trachomatis
in vitro, indicating its potential for treatment of acute and chronic
C. pneumoniae
and
C. trachomatis
infections. We investigated the effect of serial passage of two
C. pneumoniae
isolates and two serotypes of
C. trachomatis
in subinhibitory concentrations of rifalazil and rifampin on the development of phenotypic and genotypic resistance.
C. trachomatis
developed resistance to both antimicrobials within six passages, with higher level resistance to rifampin (128 to 256 μg/ml) and lower level resistance to rifalazil (0.5 to 1 μg/ml).
C. pneumoniae
TW-183 developed only low-level resistance to rifampin (0.25 μg/ml) and rifalazil (0.016 μg/ml) after 12 passages.
C. pneumoniae
CWL-029 failed to develop resistance to either drug. Two unique mutations emerged in the
rpoB
gene of rifampin (L456I) and rifalazil (D461E)-resistant
C. pneumoniae
TW-183. A single mutation (H471Y) was detected in both rifampin- and rifalazil-resistant
C. trachomatis
UW-3/Cx/D, and a unique mutation (V136F) was found in rifalazil-resistant BU-434/L
2
. No mutations were detected in the entire
rpoB
gene of rifampin-resistant BU-434/L
2
. This is the first description of antibiotic resistance-associated mutations in
C. pneumoniae
and of rifampin resistance in
C. trachomatis
not associated with mutations in the
rpoB
gene.
Biological Characterization of Novel Inhibitors of the Gram-Positive DNA Polymerase IIIC Enzyme
Authors: Kuhl Alexander , Svenstrup Niels , Ladel Christoph , Otteneder Michael , Binas Annegret , Schiffer Guido , Brands Michael , Lampe Thomas , Ziegelbauer Karl , Rübsamen-Waigmann Helga , Haebich Dieter , Ehlert Kerstin
Published: February 2005

Novel N-3-alkylated 6-anilinouracils have been identified as potent and selective inhibitors of bacterial DNA polymerase IIIC, the enzyme essential for the replication of chromosomal DNA in gram-positive bacteria. A nonradioactive assay measuring the enzymatic activity of the DNA polymerase IIIC in gram-positive bacteria has been assembled. The 6-anilinouracils described inhibited the polymerase IIIC enzyme at concentrations in the nanomolar range in this assay and displayed good in vitro activity (according to their MICs) against staphylococci, streptococci, and enterococci. The MICs of the most potent derivatives were about 4 μg/ml for this panel of bacteria. The 50% effective dose of the best compound (6-[(3-ethyl-4-methylphenyl)amino]-3-{[1-(isoxazol-5-ylcarbonyl)piperidin-4-yl]methyl}uracil) was 10 mg/kg of body weight after intravenous application in a staphylococcal sepsis model in mice, from which in vivo pharmacokinetic data were also acquired.
High bone mineral density in loaded skeletal regions of former professional football (soccer) players: what is the effect of time after active career?
Authors: Uzunca K , Birtane M , Durmus-Altun G , Ustun F
Published: February 2005

Objectives:Physical exercise is an important factor in the acceleration and maintenance of bone mineral density (BMD). Football is an impact loading sport and some studies demonstrate its site specific, bone mass increasing effect. We compared BMD at different skeletal regions in a group of former professional football players and in normal control subjects and evaluated the effect of demographic factors and time after active career on BMD.

Methods:Twenty four former football players <70 years old who had retired from professional football at least 10 years previously and 25 non-athletic controls were recruited. The demographic characteristics, activity levels, and dietary habits of all subjects and the chronological history of the footballers’ professional careers were noted. BMD was measured by DEXA at the calcaneus and distal tibia and at the lumbar spine, proximal femur, and distal and proximal radius, and compared between groups. Stepwise multiple linear regression analysis was used to determine the probable predictors of BMD in former football players.

Results:In former players BMD values were found to be significantly higher at the lumbar spine, femur neck, femur trochanter, distal tibia, and calcaneus, but not at Ward’s triangle (femur) or the distal and proximal radius regions compared with controls. Time after active career was the only independent predictor of BMD at the lumbar spine, proximal femur (neck, trochanter, and Ward’s triangle), and distal tibia.

Conclusions:Former footballers had higher BMD at weight loaded sites and time after active career seemed to be an important factor in determining BMD.
Diffusely increased bone scintigraphic uptake in patellofemoral pain syndrome
Authors: Näslund J E , Odenbring S , Näslund U-B , Lundeberg T
Published: February 2005

Objectives:Painful disorders of the patellofemoral joint are one of the most frequent complaints in orthopaedic and sports medicine. The aims of this study were to determine whether bone scintigrams of patients suffering from patellofemoral pain syndrome (PFPS) show diffuse uptake and in what bony compartment of the knee uptake, if any, was localised.

Methods:Fifty eight patients with chronic PFPS were examined. All patients underwent a detailed clinical history and a thorough physical examination of the knee. Anterior and lateral static images of both knees were made using a gamma camera 3 h after injection of 550 MBq of99mTc-HMDP. Two experienced radiologists visually evaluated the scans blindly and separately. As 51 patients had bilateral pain, 109 painful knees are included in the results.

Results:Diffuse uptake on bone scintigrams was found in 48 knees in 30 of the patients. In 33 knees the uptake was localised to only one bone compartment, in 10 knees diffuse uptake was found in two of the bones forming the knee joint, and in six knees all three bone compartments (the distal femur, the patella, and the proximal tibia) exhibited diffuse uptake.

Conclusions:Scintigrams of approximately half of the patients with PFPS will show diffuse uptake in one or more of the bony compartments of the knee joint and radioactive tracer accumulation will occur as often in the proximal tibia as in the patella.
Genomic organization and evolution of the 5S ribosomal DNA in the ancient fish sturgeon
Authors: Robles Francisca , de la Herrán Roberto , Ludwig Arne , Rejón Carmelo Ruiz , Rejón Manuel Ruiz , Garrido-Ramos Manuel A
Published: February 2005

Ribosomal DNA in sturgeon is informative when analyzed at the molecular level because it bears unique characteristics that are, to a certain extent, ancestral within vertebrates. In this paper, we examine the structure and the molecular evolution of the 5S ribosomal DNA (rDNA) region in 13 sturgeon species, comparing both the 5S ribosomal RNA (rRNA) genes and the non-transcribed spacer (NTS) sequences between the coding regions. We have found that different NTS and 5S gene variants are intermixed in the 5S rDNA arrays of the different sturgeon species and that all variants are ancestral, having been maintained over many millions of years. Using predictive models, we have found similar levels of sequence diversity in the coding regions, as well as in the non-coding region, but fixed interspecific differences are underrepresented for 5S genes. However, contrary to the expectations, we have not found fixed differences between NTS sequences when comparing many pairs of species. Specifically, when they belong to the same phylogeographic clade of the four into which the sturgeon is divided, but fixation of mutations and divergence is found between species belonging to different phylogeographic clades. Our results suggest that the evolution of the two parts of the 5S rDNA region cannot be explained exclusively as the outcome of a balance between mutational, homogenizing (i.e., gene conversion as a predominant force in sturgeon), and selective forces. Rather, they suggest that other factors (i.e., hybridization) might be superimposed over those forces and thus could to some extent be masking their effects.Key words: sturgeon, 5S rDNA, NTS sequence, 5S gene, concerted evolution, sequence homogenization, gene conversion, hybridization.