bluuebunny/crossref_metadata_2025 huggingface dataset:
Head and Neck Cancer Susceptibility: A Genetic Marker in the Methylenetetrahydrofolate Reductase Gene
Authors: Kureshi Nelofar , Ghaffar Shehzad , Siddiqui Sammer , Salahuddin Iftikhar , Frossard Philippe M.
Published: December 2004

Progress in the elucidation of molecular genetic changes that lead to the development of tumors should soon bring novel diagnostic and therapeutic procedures into clinical practice. In this respect, methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism that affects DNA methylation and synthesis. DNA methylation is an epigenetic feature that influences cellular development and function. Germ line mutation C>T at nucleotide 677 of the MTHFR gene, which results in increased thermolability and diminished enzyme activity, is oncogenic, i.e. should be a contributor to molecular changes leading to cancerous phenotypes (it has also been shown independently to be implicated in cardiovascular disease phenotypes). Interestingly, it has been shown that MTHFR T677 allele homozygosity confers a sixfold increased risk for esophageal squamous cell carcinoma in Northern China. The purpose of this study was twofold: (1) to evaluate the putative association of MTHFR C677T and epithelial squamous cell carcinoma (ESCC) in Pakistan, and (2) to investigate whether de novo MTHFR C677T mutations are involved in the determination of ESCC phenotypes. We recruited 50 ESCC patients referred to the Otolaryngology Clinic of the Aga Khan University Hospital, and 54 age- and gender-matched control (disease-free) subjects. Our results show that T allele frequencies were 0.18 ± 0.05 in cases vs. 0.24 ± 0.05 in controls (as compared with 0.63 vs. 0.41 in the report from China). Although the association is not statistically significant, T alleles are actually more common amongst controls in the Pakistani population, which is the opposite of what would be expected and what has been reported amongst Chinese. Yet the frequency of deleterious T alleles is lower in Pakistan (range 0.18–0.24) than in other parts of the world. Our results indicate that MTHFR C677T cannot form the basis for a genetic test aimed at evaluating an individual’s genetic susceptibility to ESCC in Pakistan. As the conversion of precancerous submucous fibrosis into overt cancer is a frequent occurrence in Pakistan, we proceeded to extract DNA samples in all ESCC patients, from whole blood, cancerous tissues and neighboring normal tissues. We sought to determine whether C677T genotypes were different in the three tissue samples from each ESCC patient. In all patients, identical genotypes (and therefore allele frequencies) were systematically observed in all three samples. This indicates that de novo MTHFR 677TC>T mutations are not part of the molecular etiology of ESCC. In conclusion, we can rule out a major involvement of the MTHFR gene in the determination of ESCC in Pakistan.
The Characteristic Features of Muscle Tension Dysphonia before and after Surgery in Benign Lesions of the Vocal Fold
Authors: Hsiung Ming-Wang , Hsiao Yu-Che
Published: December 2004

Muscular tension dysphonia (MTD) is often concomitant in patients with underlying glottic insufficiency. It remains unclear, however, whether the characteristic features of MTD appear independently or as a consequence of dysphonia. We report here on a retrospective study of the prevalence of the four prominent characteristic features of MTD, as described by the Morrison-Rammage classification, in patients with benign lesions of the vocal fold. Two otorhinolaryngologists, independent of one another, rated the preoperative and postoperative videolaryngostroboscopic results of 260 patients to assess the presence or absence of MTD. Of the 260, 185 had vocal nodules, 49 had vocal polyp, and 26 had vocal cyst. Postoperative follow-up examinations were conducted for a period ranging from 4.5 to 35 months (mean = 18.5 months). Patient ages ranged from 18 to 76 years (mean = 47.3 years). Nearly 90% of the preoperative patients in our study cohort exhibited at least one of the MTD characteristic features. Approximately 74% of postoperative ‘asymptomatic’ patients in our study cohort exhibited at least one characteristic feature. As the characteristic features of MTD were found in both preoperative dysphonic patients and those patients who were successfully treated, MTD etiology may be causal (type I), concomitant (type IIa, IIb, III) or psychogenic (type IIa, IIb). Therefore characteristic features of MTD cannot be adequately resolved through surgery, and treatment should be supplemented by speech therapy to achieve the greatest effect in causal type I MTD.
Mandarin Speech Perception in Nucleus CI 24 Implantees Using MAPs Based on Neural Response Telemetry
Authors: Sun Yu-Sheng , Wu Che-Ming , Liu Tien-Chen
Published: December 2004

The purpose of this study is to compare speech perception performance in Mandarin-speaking Nucleus CI24 implantee using standard behavior MAPs and NRT-based MAPs. Eight Nucleus CI24 users (5 years and older) participated in the study. They all fulfilled the following criteria: (1) behavioral MAP and NRT thresholds can be reliably obtained; (2) had more than 18 functioning electrodes; (3) had at least 6 months experience using CI. All subjects received speech evaluation under three different MAPs: a traditional behavioral MAP, a MAP predicted from the NRT thresholds of the E22 (electrode 22), E19, E15, E11, E8, E5, E1 and a combined MAP based on the information of NRT thresholds and behavioral threshold/comfortable levels of the E11. The speech evaluation package included word recognition test in quiet, in noise, and a Mandarin sentence test in quiet. Results showed that three MAPs are similar in some subjects, but different in other subjects. Compared to the NRT MAPs, the combined MAPs are more similar to the behavioral MAPs. There was no significant difference in the mean score of the word recognition test in quiet, in noise and sentence test under these three MAP conditions. In conclusion, although the behavioral MAPs and the NRT-based MAPs are not identical, the speech performance of Mandarin-speaking CI24 implantee using MAPs predicted from NRT thresholds appeared to be no worse than the traditional behavioral MAPs. Therefore, in certain cases that behavioral MAPs are difficult to obtain (such as in very young or multiple handicapped children), NRT-based MAPs may serve reliably as an initial estimation.
Use of Cross-Sectional Imaging in Predicting Facial Nerve Sacrifice during Surgery for Parotid Neoplasms
Authors: Divi Vasu , Fatt Michael A. , Mukherji Suresh K. , Bradford Carol R. , Chepeha Douglas B. , Wolf Gregory T. , Teknos Theodoros N.
Published: December 2004

Background: Neoplasms of the parotid gland are difficult management issues because of the wide variation in their biological behavior and the potential for sacrifice of the facial nerve during resection. Because of the significant associated morbidity, prediction of facial nerve sacrifice is critically important for planning surgical procedures and preoperative counseling of patients. We hypothesize that along with the knowledge of the tumor type we would be able to accurately predict the likelihood of facial nerve sacrifice using cross-sectional imaging. Methods: All patients included in this study were previously untreated patients with parotid neoplasms operated on between January 1997 and July 2002. Only those patients with an available preoperative imaging were included and this resulted in 44 patients for review. Nine patients with preoperative deficits in facial nerve function were excluded from this study since these patients would require facial nerve sacrifice regardless of the radiological prediction. The prediction of facial nerve sacrifice was determined using a prediction of tumor location and an algorithm. The predicted results were compared to the operative record. Results: For all lesions, cross-sectional imaging predicted the need for sacrifice of the facial nerve with a sensitivity of 0.83 (95% CI, 0.36–0.99), specificity of 0.90 (95% CI, 0.72–0.97), PPV of 0.63 (95% CI, 0.26–0.90), and NPV of 0.96 (95% CI, 0.79–0.99). For malignant lesions only, prediction of sacrifice of the facial nerve had a sensitivity of 0.83 (95% CI, 0.36–0.99), specificity of 0.80 (95% CI, 0.51–0.95), PPV of 0.63 (95% CI, 0.26–0.90), and NPV of 0.92 (95% CI, 0.62–0.99). Conclusion: Cross-sectional imaging and application of our algorithm is a sensitive method for identifying patients with parotid neoplasms who require facial nerve sacrifice. CT and MRI have a high negative predictive value for facial nerve sacrifice.
Electronic Videoendoscopic Laryngostroboscopy
Authors: Kawaida Masahiro , Fukuda Hiroyuki , Kohno Naoyuki
Published: December 2004

Color images obtained using electronic videoendoscopic laryngostroboscopy (EVLS) were presented and the utility of this technique for the diagnosis of dysphonia was discussed in this paper. Stroboscopic evaluations of laryngeal lesions were performed using a rhinolaryngeal electronic videoendoscope system employing a single-plate simultaneous color charge-coupled device (CCD) chip method. Twenty patients underwent electronic videoendoscopic laryngostroboscopy. A Karl Storz laryngostroboscope Pulsar was connected to this system and laryngeal lesions were assessed. The potentialities of laryngostroboscopy using this system were evaluated. Clear stroboscopic images were obtained in all patients. Multiple still images during vocal fold vibration were acquired using an optional function. The laryngostroboscope is not compatible with conventional systems employing a single-plate red, green, and blue (RGB) surface scanning method. However, the system used was successfully connected to a laryngostroboscope. EVLS appears to be a powerful new tool for the diagnosis of dysphonia.
Vitamin E Can Protect against Ultraviolet Radiation-Induced Cataract in Albino Rats
Authors: Ayala Marcelo N. , Söderberg Per G.
Published: December 2004

Purpose: To investigate if vitamin E protects against ultraviolet B radiation (UVB)-induced cataract. Methods: Albino Sprague-Dawley rats were divided into two groups: one group was fed vitamin E, while the other group was used as a control. Both groups were exposed to UVB. The rats were sacrificed, lenses extracted, forward light scattering was measured, and vitamin E and glutathione (GSH) contents were determined. Results: Lenses in the vitamin E group developed slight opacities, while lenses in the control group developed nuclear cataracts. Forward light scattering in lenses of the control group was higher than in lenses in the vitamin-E-supplemented group. Vitamin E and GSH concentrations were higher in lenses treated with vitamin E than in the untreated group. Conclusions: Vitamin E protects the lens against UVB-induced cataract. Vitamin E protects directly as an antioxidant and/or indirectly through increased levels of GSH.
Transient Severe Eosinophilia Precipitating Massive Venous Thrombosis in a Patient with Hereditary Thrombophilia
Authors: Mates Michal , Nesher Gideon , Roth Batia , Rosenberg Rina , Heyd Judith , Hershko Chaim
Published: December 2004

We describe a patient homozygous for both the prothrombin G20210A and methylenetetrahydrofolate reductase C667T mutations who was symptom-free for 40 years and developed near-catastrophic thrombotic complications following transient, severe eosinophilia. This course of events raises the possibility of an increased risk of thrombosis associated with transient eosinophilia in the presence of hereditary thrombophilia and supports the concept of multifactorial etiology of venous thrombosis. Our experience suggests that in patients with severe eosinophilia, evaluation for known causes of hereditary or acquired thrombophilia may be useful for identifying subjects at increased risk of thrombosis.
Very Late Central Nervous System Relapse in a Patient with B Cell Lymphoblastic Lymphoma
Authors: Nagasaki Akitoshi , Miyagi Takashi , Nakazato Tetsuro , Taira Naoya , Ohshima Koichi , Kikuchi Masahiro , Takasu Nobuyuki , Masauda Masato
Published: December 2004

Very late relapse of lymphoblastic lymphoma (LBL) is very rare. We report a case of a patient who developed central nervous system (CNS) relapse of LBL 16 years after the onset of the primary disease. An 8-year-old girl was hospitalized with a skin tumor in the occipital region on November 27, 1984. Examination of a biopsy of the skin tumor showed typical features of non-Hodgkin’s lymphoma (diffuse medium-sized cell type). She received multiagent chemotherapy and went into remission. On July 4, 2000, she was hospitalized with persistent headache. Cranial magnetic resonance imaging showed a cerebellar lesion, which was hypointense on T1-weighted images and of heterogeneous intensity on T2-weighted images. A midline suboccipital craniotomy was performed and pathological examination revealed a diffuse proliferation of lymphoid cells, which were positive for terminal deoxynucleotidyl transferase, but negative for CD45RO, CD3 and CD20. Tumor cells stained positively for CD10, CD22, CD38 and HLA-DR. Revised immunohistochemistry of the primary specimens of skin tumor obtained 16 years earlier revealed a phenotype similar to that of the CNS disease. Polymerase chain reaction products for the immunoglobulin gene from both the skin and cerebellar specimens were an identical size. Thus, the original diagnosis of diffuse medium-sized lymphoma was revised to B cell LBL. An isolated CNS relapse of LBL was apparent in the present case. After salvage chemotherapy, the patient underwent high-dose chemotherapy with autologous peripheral blood stem cell support and subsequent craniospinal irradiation. She went into a lasting complete remission.
Greek M.D. Anderson Symptom Inventory: Validation and Utility in Cancer Patients
Authors: Mystakidou Kyriaki , Cleeland Charles , Tsilika Eleni , Katsouda Emmanuela , Primikiri Aphrodite , Parpa Efi , Vlahos Lambros , Mendoza Tito
Published: December 2004

Objective: The M.D. Anderson Symptom Inventory (MDASI) is a brief assessment of the severity and impact of cancer-related symptoms. The purpose of this study was the translation and validation of the questionnaire in Greek (G-MDASI). Methods: The translation and validation of the assessment took place at a Pain Relief and Palliative Care Unit. The final validation sample included 150 cancer patients (61 males, 89 females, age range 31–88 years, mean age 63.32). The patients completed the questionnaires at the outpatient clinic. Assessing the validity and reliability constituted the actual validation of the G-MDASI. Results: The item ‘diarrhea’ had a score of 0 in 139 patients and, thus was omitted from the ‘core’ list. Consequently, the core questionnaire consisted of 14 items. Factor analysis resulted in a 3-factor model, in both validation and cross-validation samples. The examination of the sensitivity of the MDASI revealed that there were differences between patients with poor-to-good performance status but no differences were found between patients in different treatment groups. Conclusions: The results showed that the G-MDASI is a reliable and valid measure in Greek cancer patients. It has proved to be a comprehensive symptom assessment tool.
Phase II Study of Pegylated Liposomal Doxorubicin in Heavily Pretreated Epithelial Ovarian Cancer Patients
Authors: Lorusso D. , Naldini A. , Testa A. , D’Agostino G. , Scambia G. , Ferrandina G.
Published: December 2004

Objective: Pegylated liposomal doxorubicin (PLD) has shown promising activity in the treatment of recurrent ovarian cancer but skin toxicity remains the dose-limiting toxicity of the drug. The aim of this study was to investigate whether a different treatment schedule may improve the toxicity profile, especially in terms of dermatological and mucosal toxicity. Methods: It is an open-label phase II study in a population of heavily pretreated ovarian cancer patients. PLD was administered at the dose of 35 mg/m2 q21 until disease progression or unacceptable toxicity. Results: Thirty-seven heavily pretreated (median number of previous chemotherapy regimens 2, range 1–6) ovarian cancer patients were enrolled. All patients received at least two courses of chemotherapy and all were evaluated for response. No one showed complete response, while five partial responses (13.5%), 16 stabilizations of disease (48.6%) and 14 progressions of disease (37.8%) were observed. The median time to response was 12 weeks (range 8–16). The median duration of response was 22.8 weeks (range 4–68), the median duration of stabilization of disease was 17.6 weeks (range 4–28). Palmar plantar erythrodysesthesia (PPE) occurred in 8 patients (21.6%) and was of grade 3 in one patient (2.8%). Grade 1 stomatitis occurred in 3 patients (8.1%). Grade 3–4 neutropenia occurred in only 4 patients (10.8%). Conclusions: PLD at the dose of 35 mg/m2 q21 seems to translate into an acceptable skin toxicity profile with a response rate comparable to others obtained with a standard schedule.
Front-Line Chemotherapy with Docetaxel and Gemcitabine Administered Every Two Weeks in Patients with Metastatic Breast Cancer: A Multicenter Phase II Study
Authors: Mavroudis D. , Malamos N. , Polyzos A. , Kouroussis Ch. , Christophilakis Ch. , Varthalitis I. , Androulakis N. , Kalbakis K. , Milaki G. , Georgoulias V.
Published: December 2004

Objective: To evaluate the docetaxel-gemcitabine combination administered every 2 weeks in women with untreated metastatic breast cancer (MBC). Methods: Fifty-two patients with MBC received docetaxel 65 mg/m2 as front-line chemotherapy intravenously over 1 h followed by gemcitabine 1,500 mg/m2 intravenously over 30 min on days 1 and 14. Cycles were repeated every 28 days without prophylactic growth factor support. Twenty-eight (54%) patients had previously received chemotherapy as adjuvant or neoadjuvant treatment. Thirty-six (69%) patients had visceral disease including 20 (38%) with liver metastases. All patients were evaluated for toxicity and 45 for response. Results: In an intention-to-treat analysis, a complete response occurred in 7 (13%) patients and partial response in 24 (46%) for an overall response rate of 59% (95% CI: 46.3–73.0%). The response rate was 68% for the 28 patients who had previously received adjuvant or neoadjuvant chemotherapy and 67% for the 36 patients with visceral metastases. The median duration of response was 6.1 months and the median time to disease progression 10.9 months. A total of 254 cycles were administered with dose reduction in 26 (10%) cycles and no lethal toxicity. Grade III–IV neutropenia occurred in 17 (33%) patients and thrombocytopenia in 3 (6%). Febrile neutropenia developed in 3 (6%) patients. Nonhematological toxicity was generally mild. Conclusion: The docetaxel-gemcitabine combination is an active and well-tolerated front-line treatment for patients with MBC. This regimen represents a suitable option especially for women relapsing after anthracycline-based adjuvant chemotherapy.
Approaches to Familial Aggregation: Hypothesis Testing and Estimation when Families Are Selected through Parent Probands under a Variant of Single Ascertainment
Authors: Wickramaratne Priya J.
Published: December 2004

Epidemiologic approaches to testing and estimating familial aggregation of a disease consist of comparing rates of disease in relatives of individuals with the disease (known as case probands) with rates of disease in relatives of individuals without the disease (known as control probands). Gold et al. (J Am Stat Ass 1967;62: 409–420) derived an explicit mathematical model and sampling methods, under which this approach is equivalent to testing the null hypotheses that the disease risk in families is homogenous. A basic assumption of this model is that every family member has the same risk of disease and that disease status is independent among family members, although the disease risk may vary between families. When the disease is suspected of having a genetic component, rather than being purely environmental, this model has been shown to be appropriate for detecting disease aggregation in siblings, when relatives are siblings of probands. This model however is unrealistic for use in nuclear families when the affected status of offspring is not independent of the affected status of parents, and these families are selected through an affected or an unaffected parent, so that a parent is the proband and relatives are offspring of probands. We extend the Gold et al. model to allow for the disease risk in offspring to vary with the affected status of the parent. We assume that families are selected through affected and unaffected parents, under a variation of single ascertainment. Under this study design, we show that the usual test of association between affected status of probands and relatives, performed by comparing sample proportions of affected relatives of affected and unaffected probands, respectively, is no longer equivalent to a test of homogeneity of disease risk in offspring. Instead, it is equivalent to testing that the disease risk in offspring is independent of the number of affected parents. This test reduces to a test of homogeneity if and only if one assumes that the variation in disease risk in offspring, between families, is solely due to the variation in the number of affected parents. As a result, we show that under this study design, the standard χ2 test must be modified in order to obtain a valid test of familial aggregation. In addition the sample proportions of affected relatives of case and control probands, respectively, are shown to provide unbiased estimates of the expected risk of disease in an offspring given an affected/unaffected parent. We apply these results to methods of sample selection and discuss the practical implications of these findings.
DFNB44, a Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus, Maps to Chromosome 7p14.1-q11.22
Authors: Ansar Muhammad , Chahrour Maria H. , Amin ud Din Mohammad , Arshad Muhammad , Haque Sayedul , Pham Thanh L. , Yan Kai , Ahmad Wasim , Leal Suzanne M.
Published: December 2004

The genetic etiology for many forms of hearing impairment (HI) is very diverse. Non-syndromic HI (NSHI) is one of the most heterogeneous traits known. Autosomal recessive forms of prelingual HI account for ∼75% of hereditary cases. A novel autosomal recessive NSHI locus, DFNB44, was mapped to a 20.9 cM genetic interval on chromosome 7p14.1-q11.22, according to the Marshfield genetic map, in a consanguineous Pakistani family. Multipoint linkage analysis resulted in a maximum LOD score of 5.0 at marker D7S1818. The 3-unit support interval ranged from marker D7S2209 to marker D7S2435, spanning a 30.1 Mb region on the sequence-based physical map.
Treatment with Fluvastatin Rapidly Modulates, via Different Pathways, and in Dependence on the Baseline Level, Inflammation in Hemodialysis Patients
Authors: Tsirpanlis George , Boufidou Fotini , Manganas Stamatios , Chantzis Konstantinos , Bleta Aliki , Stamatelou Kyriaki , Psimenou Erasmia , Nicolaou Chrysoula
Published: December 2004

Background: Hemodialysis (HD) patients are frequently in an elevated inflammatory state which is correlated to the atherosclerosis-related and overall morbidity and mortality in this population. Statins, beyond their antilipidemic effects, are also considered to have anti-inflammatory, immunomodulating and antioxidant properties. The individual response of HD patients to a short course of fluvastatin, the mechanisms involved in the immunomodulating and anti-inflammatory effects of this drug and the time interval to the appearance of these effects are investigated in this longitudinal study. Methods: In a group of 51 HD patients, fluvastatin 40 mg/day was administered for 4 weeks. Serial measurements of the lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin-10 (IL-10), and serum oxidized LDL (ox-LDL), were performed before, during, and after the treatment period. Results: Total cholesterol was significantly reduced after 14 days of treatment with fluvastatin (from mean ± SD 216.7 ± 34.3 to 179.2 ± 42.3 mg/dl, p < 0.001). IL-6 and ox-LDL were reduced on day 28 (p < 0.001 and p < 0.01, respectively) and IL-10 was increased on day 14 (p = 0.05); CRP did not change significantly during the treatment period while sIL-6R was increased on day 28 of fluvastatin administration (p < 0.05). In a subgroup of patients with CRP, IL-6, sIL-6R, and ox-LDL baseline serum values ≧ the median and IL-10 ≤ the median, CRP was reduced on day 28 of fluvastatin treatment (p < 0.01), IL-6 and ox-LDL were reduced earlier, on day 14 (p = 0.05 and p < 0.05, respectively) while sIL-6R did not change significantly during the treatment period. Conclusions: Treatment with fluvastatin rapidly modulates inflammation in HD patients. Enhancement of anti-inflammatory mechanisms and attenuation of the inflammatory and oxidative state contribute to this modulation. Patients in an elevated baseline inflammatory state respond more rapidly and effectively to the treatment. This immediate and multi-potent action of the statins could be clinically useful in acute atherosclerosis complications or in the treatment of chronic inflammation in HD patients.
Transcription-Based Solenoidal Model of Chromosomes
Authors: Képès François , Vaillant Cédric
Published: December 2004

The organization of transcription within the eukaryotic nucleus or the prokaryotic nucleoid may be expected to both depend on and determine the structure of the chromosomes. In yeast and bacteria, genes that are controlled by the same sequence-specific transcription factor tend to be either clustered or regularly spaced along the chromosomes. The same spacing is found for most transcription factors within a chromosome. Furthermore, in bacteria, the gene encoding the transcription factor tends to locate at identical regular intervals from its targets. This periodicity is consistent with a solenoidal epi-organization of the chromosome, which would dynamically gather the interacting partners into foci. Binding at genuine regulatory sites on DNA would thus be optimized by locally increasing the concentration of transcription factors and their binding sites. As many transcription factors are simultaneously active and some share targets, the resulting collection of foci provides a potent self-organizational principle for the chromosome, and consequently for the functional nuclear architecture.
Late Complications of Diabetes mellitus in the Republic of Uzbekistan
Authors: Ismailov S.I. , Berdykulova D.M. , Khaidarova F.A.
Published: December 2004

Background: Diabetes mellitus (DM) is a major cause of blindness, and cardiovascular risk is the highest in diabetics. More than 40% of all trauma-unrelated lower extremity amputations are performed because of diabetic foot syndrome and lower extremity gangrene; 35–40% of all deaths due to uremia occur in diabetics. Objective: To study the prevalence of late complications of DM in the Republic of Uzbekistan and risk factors contributing to their progression. Methods: 1,000 and 1,141 patients with type 2 DM, resident in urban and rural areas of Uzbekistan, respectively, underwent general clinical examination in which arterial pressure, carbohydrate and lipid metabolism parameters were measured. A special questionnaire was filled out for each patient. Results: The study established a higher prevalence of late complications of DM in urban diabetics as compared with those in rural regions (p < 0.001). The incidence of macroangiopathies of lower extremity vessels, diabetic foot syndrome and myocardial infarction was found to be higher in males than that in females, while the prevalence of ischemic heart disease was registered as higher in females regardless of region. An increase in the incidence of late complications of DM with disease duration was found in residents of both regions (p < 0.001). The prevalence of macroangiopathies, diabetic polyneuropathy and diabetic foot syndrome in the decompensated stage of disease was high among both urban and rural residents. The smokers had a higher prevalence of diabetic retinopathy, macroangiopathies of lower extremity vessels, myocardial infarction and ischemic heart disease regardless of region. Age also contributes to the progression of late complications of DM. Conclusions: The incidence of late complications of DM was higher in urban diabetics than in their rural counterparts in the present study. Sex, age, disease duration, compensation stage and bad habits were found to be risk factors for the progression of late complications of DM.
Age-Dependent Therapeutic Effects of Once-Daily Molsidomine Used as an Add-On Treatment in Patients with Stable Angina pectoris
Authors: Messin Roger , Carreer-Bruhwyler Fabienne , Dubois Claude , Famaey Jean-Pierre , Géczy Joseph
Published: December 2004

Background: A once-daily 16-mg-dose formulation of molsidomine (Coruno® tablets) was recently developed for the chronic treatment of angina pectoris. It required efficacy and safety testing. Objective: The objective of the present study was to compare the efficacy and tolerability of Coruno with that of the currently prescribed twice-daily 8-mg dose of molsidomine (Corvatard® tablets), using them as add-on therapies in patients with stable angina pectoris aged either less or more than 75 years. Methods: 133 patients (including 55 elderly patients of at least 75 years) received molsidomine 8 mg twice daily (M8) for at least 1 month as add-on therapy before enrollment. The study itself consisted of a 1-week period during which patients went on with M8, followed by a 4-week period during which M8 was replaced by molsidomine 16 mg once daily (M16). The frequency of anginal attacks and short-acting nitroderivative consumption for symptomatic relief were measured, and the quality of life was assessed by validated questionnaires. Results: M16 significantly reduced the incidence of anginal attacks in elderly patients compared with M8. The same significant benefit was not observed in younger patients. A nonsignificant decrease in the consumption of nitroderivatives for pain relief was recorded in both age groups. From 3 weeks of treatment, M16 did not induce more drug-related adverse events than M8. It had no significant effect on blood pressure, heart rate or ECG. Conclusions: M16 was as safe and effective as M8 in controlling angina, reducing the frequency of anginal attacks even more in the elderly compared with the younger patient group.
Peripheral Chemoreceptor Contributions to Cardiovascular Regulation
Authors: Shoemaker J. Kevin
Published: December 2004

Oxygen homeostasis at the cellular level depends on acute and appropriate cardiovascular adjustments elicited by neural chemosensitive reflexes. This review addresses the integrated physiology of peripheral chemoreflex control of cardiovascular function with emphasis on the relevance for the intact and conscious human. Peripheral chemoreceptor activation affects sympathoexcitatory and cardiovascular responses that can be modified by the concurrent effects of enhanced ventilation. Additional changes in baroreflex control during chemoreceptor activation must be considered in determining chemoreflex-mediated cardiovascular regulation. Moreover, the autonomic response elicited by the peripheral chemoreflex may enhance the sensitivity of these chemoreceptors, further enhancing or prolonging the neural and cardiovascular consequences of hypoxia. Finally, the recent interest in the role of altered chemoreflex sensitivity and function in cardiovascular pathology is highlighted. The collective information suggests that these interactions may contribute importantly to cardiovascular pathology requiring considerable research into the linkage between cellular and genomic mechanisms that affect the integrated systems response in health and disease.
Methods for the Evaluation of Vascular Reconstruction
Authors: Stranden Einar
Published: December 2004

Despite carefully performed surgery, vascular defects can remain undetected within an arterial reconstruction after blood flow is restored. Failure to recognize technical errors or abnormalities can lead to vessel thrombosis and embolization. For cardiac, carotid or visceral reconstructions these events can be catastrophic. Furthermore, corrections of lesions before graft thrombosis can have a significant impact on long-term patency, being particularly important for vein grafts, because most will not maintain patency with thrombectomy alone. This review describes methods for peroperative evaluation of vascular reconstructions. Since careful selection of patients for therapy as well as proper postoperative surveillance contribute to the success of vascular surgery, some methods for pre- and postoperative evaluation are also included.
Iron and Oxidative Stress in Renal Insufficiency
Authors: Lim Chun Soo , Vaziri Nosratola D.
Published: December 2004

Background/Aims: Iron (Fe) can cause tissue injury and oxidative stress by catalyzing hydroxyl radical production and lipid peroxidation. Intravenous (i.v.) Fe preparations are routinely administered to treat anemia in patients with chronic renal failure (CRF), a condition marked by oxidative stress and inflammation. In an earlier study, we showed that iron overload augments oxidative stress in the cardiovascular tissues of CRF rats. This study was designed to expand these observations to other major organs. Methods: Rats were randomized into CRF (5/6 nephrectomized) and sham-operated control (CTL) groups. Each group was subdivided into Fe-loaded (single i.v. injection of iron dextran complex, 0.5 g/kg) and placebo-treated subgroups. After 13 weeks, systolic blood pressure, blood hemoglobin (Hb), plasma Fe concentration, lipid peroxidation products, superoxide generating enzyme, NAD(P)H oxidase, and antioxidant enzymes were determined. Results: Systolic blood pressure was equally elevated and creatinine clearance was equally reduced in both CRF groups. Fe administration raised Hb, serum Fe and transferrin saturation in both CRF and CTL groups. The plasma concentration of lipid peroxidation product, malondialdehyde, was increased by Fe injection in CRF rats but not the control group. Renal tissue abundance of gp91phox subunit of NAD(P)H oxidase was elevated in the untreated CRF group and was partially reduced in the iron dextran-treated CRF group. Tissue abundance of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were decreased in both untreated and iron dextran-treated CRF groups. Conclusion: CRF resulted in marked SOD, CAT and GPX deficiencies. A single i.v. administration of iron dextran in rats with CRF induced oxidative stress as measured by increased lipid peroxidation products and decreases in antioxidant enzymes.
Efficacy of Multidrug Therapy Combined with Mizoribine in Children with Diffuse IgA Nephropathy in Comparison with Multidrug Therapy without Mizoribine and with Methylprednisolone Pulse Therapy
Authors: Kawasaki Yukihiko , Hosoya Mitsuaki , Suzuki Junzo , Onishi Noriko , Takahashi Ai , Isome Masato , Nozawa Ruriko , Suzuki Hitoshi
Published: December 2004

Aim: To evaluate the efficacy of prednisolone, warfarin, and dipyridamole therapy combined with mizoribine (PWDM) in the treatment of diffuse immunoglobulin A (IgA) nephropathy in comparison with prednisolone, warfarin, and dipyridamole therapy without mizoribine (PWD) and with methylprednisolone pulse therapy (PWD pulse). Methods: We collected data on 61 patients diagnosed with diffuse IgA nephropathy, and these patients were retrospectively divided into three groups without randomization. Group A included 21 patients before 1987 who were treated with PWD for 24 months, group B included 20 patients from 1987 to 1989 who were treated with PWD pulse therapy for 24 months, and group C included 20 patients after 1990 who were treated with PWDM for 24 months. Clinical features and pathological findings in each group were analyzed retrospectively. Results: The time from initiation of therapy in group A, group B, and group C was 8.9 ± 5.2, 8.1 ± 3.9, and 7.7 ± 3.8 years, respectively. At the latest follow-up examination, the mean urinary protein excretion (mg/m2/h) was 17 ± 10 in group A, 22 ± 20 in group B, and 6 ± 6 in group C and had decreased significantly in group C as compared with the other groups. The activity index in all three groups was lower at the second biopsy than that at the first biopsy (5.1 ± 0.8 vs. 6.5 ± 2.1 in group A, p < 0.05; 5.6 ± 0.9 vs. 6.6 ± 1.7 in group B, p < 0.01, and 4.5 ± 1.0 vs. 6.8 ± 1.9 in group C, p < 0.01). The chronicity index in groups A and B at second biopsy was higher than at first biopsy (7.3 ± 1.4 vs. 4.8 ± 1.0 in group A, p < 0.01, and 8.1 ± 2.0 vs. 5.3 ± 0.9 in group B, p < 0.01), but was unchanged in group C. At the latest follow-up examination, 1 patient (4.8%) in group A, 3 patients (15%) in group B, and none (0%) in group C had renal insufficiency. Conclusion: These results suggest that PWDM appears to be more effective than PWD or PWD pulse in ameliorating proteinuria and histological severity of patients with IgA nephropathy.
Autoimmune Hepatitis – Sequel of a Relapsing Hepatitis A in a 75-Year-Old Woman
Authors: Grünhage F. , Spengler U. , Fischer H.P. , Sauerbruch T.
Published: December 2004

Acute hepatitis A virus (HAV) infection is a global cause of acute hepatitis. However, chronic HAV infection is unlikely. Nevertheless, there is some evidence that acute infection with HAV may trigger chronic active hepatitis which fulfils the criteria of autoimmune hepatitis (AIH). Whether AIH following HAV infection is virus specific remains unclear. Despite evidence that inherited factors may play a role in the development of autoimmunity after viral infection, the pathomechanism remains unclear. We describe a 75-year-old woman with a history of pulmonary sarcoidosis who developed AIH after acute HAV infection.
Life-Long Echoes – A Critical Analysis of the Developmental Origins of Adult Disease Model
Authors: Gluckman Peter D. , Hanson Mark A. , Morton Susan M.B. , Pinal Catherine S.
Published: December 2004

The hypothesis that there is a developmental component to subsequent adult disease initially arose from epidemiological findings relating birth size to either indices of disease risk or actual disease prevalence in later life. While components of the epidemiological analyses have been challenged, there is strong evidence that developmental factors contribute to the later risk of metabolic disease – including insulin resistance, obesity, and heart disease – as well as have a broader impact on osteoporosis, depression and schizophrenia. We suggest that disease risk is greater when there is a mismatch between the early developmental environment (i.e., the phase of developmental plasticity) versus that experienced in mature life (i.e., adulthood), and that nutritional influences are particularly important. It is also critical to distinguish between those factors acting during the developmental phase that disrupt development from those influences that are less extreme and act through regulated processes of epigenetic change. A modelof the relationship between the developmental and mature environment is proposed and suggests interventional strategies that will vary in different population settings.
Long-Term Adaptation of Renal Ion Transporters to Chronic Diuretic Treatment
Authors: Kim Gheun-Ho
Published: December 2004

Loop and thiazide diuretics are clinically useful to induce negative sodium balance. However, with chronic treatment, their effects tend to be blunted since the kidney adapts to diuretics. Molecular identification of the renal ion transporters has provided us with a new understanding of the mechanisms of intrarenal adaptation to diuretics at molecular levels. In the kidney, loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 (OAT1) and exert their diuretic action by binding to the Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and the Na-Cl cotransporter (NCC) in the distal convoluted tubule, respectively. Recent studies in animal models suggest that abundance of these ion transporters is affected by long-term diuretic administration. Downstream from the primary site of diuretic action, an increase in epithelial Na+ channel (ENaC) abundance is induced by chronic furosemide or hydrochlorothiazide treatment. This adaptation is consistent with previous reports showing cellular hypertrophy and increased Na+ absorption in distal tubular segments. The abundance of NKCC2 and NCC is increased by furosemide and hydrochlorothiazide, respectively. This compensatory upregulation suggests that either diuretic may activate the ion transporter within the primary site of action. In the proximal tubule, the abundance of OAT1 is increased by chronic treatment with furosemide or hydrochlorothiazide. This upregulation of OAT1 seems to be induced by substrate stimulation, lessening diuretic tolerance associated with long-term diuretic use.
Treatment of Postoperative Enterocutaneous Fistulas by High-Pressure Vacuum with a Normal Oral Diet
Authors: Medeiros Aldo Cunha , Aires-Neto Tertuliano , Marchini Julio Sérgio , Brandão-Neto Jose , Valença Dione Maria , Egito Eryvaldo Sócrates Tabosa
Published: December 2004

Background/Aims: Enterocutaneous fistulas are associated with prolonged hospital stay, high morbidity/mortality, and increased hospital costs. This study aims to describe the use of a vacuum system and normal oral diet in dealing with this problem. Methods: Seventy-four consecutive patients with recent and defined external postoperative fistulas were analyzed. Abdominal imaging was used to exclude abscess and distal obstruction. The fistula tract was sealed with Foley catheter, connected to a negative pressure flask, changed daily for 5, 10 or 15 days, as necessary. A normal oral diet was permitted. Results: No patient died. Serum albumin and transferrin showed significantly higher levels at the end of treatment than at the beginning. The moderate and low-output fistulas had the best results (97% closed). Forty-eight (65%) fistulas closed after 5 days, 16 (22%) after 10 days and 4 (5%) after 15 days. Treatment failed in 6 (8%) patients, who subsequently underwent surgery. The fistula did not close in 1 patient with a low output. The cost of the treatment was USD 41.75/day and it was considered cost-effective. Conclusions: The vacuum system demonstrated good results in the treatment of fistulas. It included simplicity, low cost, short hospital stay, absence of skin breakdown, normal eating, good nutrition and activity patterns.
Correlation between Dynamic Computed Tomographic and Histopathological Findings in the Diagnosis of Small Hepatocellular Carcinoma
Authors: Sakabe Katsu , Yamamoto Takatsugu , Kubo Shoji , Hirohashi Kazuhiro , Hamuro Masao , Nakamura Kenji , Inoue Yuichi , Kaneda Kenji , Suehiro Shigefumi
Published: December 2004

Background/Aims: To determine the characteristic image findings on dynamic computed tomography (CT) for small hepatocellular carcinoma (HCC), we evaluated the correlation of histopathological and radiological findings with respect to the angioarchitecture in small HCCs. Methods: CT and early- and late-phase dynamic CT findings of 80 small HCCs (≤3 cm) were divided into iso-, high, low, and mixed density. We studied the correlation between the imaging findings and the histopathological findings as follows: differentiation grade; presence of fibrous capsule; presence of Glisson’s sheath, and growth pattern. Results: High-density early-phase CT and low-density late-phase CT correlated significantly with moderately/poorly differentiated HCCs, which have a fibrous capsule, no Glisson’s sheath, and an expansive growth pattern. In contrast, well-differentiated HCCs with a Glisson’s sheath and a replacing pattern (early HCC) appeared as iso-dense lesions in the early and late phases. Well-differentiated HCCs (non-early wHCC) demonstrated various density images in the early phase and low-density images in the late phase. Conclusions: Dynamic CT is an economic and simple diagnostic tool for planning treatment of small HCC lesions because of the multistep nature of HCC carcinogenesis and the hemodynamic changes of tumor blood flow.
Novel Insertion 496_497insG Creating a Stop Codon D194X in a Chinese Family with X-Linked Adrenoleukodystrophy
Authors: Mak Chloe M. , Lam Karen S.L. , Ma Oliver C. , Tso Annette W.K. , Tam Sidney
Published: December 2004

X-linked adrenoleukodystrophy (XALD, MIM 300100), the commonest inherited peroxisomal disorder, is characterized by central nervous system demyelination, primary adrenal failure and the systemic accumulation of saturated very long chain fatty acids (VLCFAs). The defective gene ABCD1 encodes an ATP-binding cassette (ABC) transport protein named ALDP, which functions as a crucial transporter of VLCFAs into the peroxisomes for β-oxidation. Here, we report a Chinese man with adrenomyeloneuropathy characterized by Addison’s disease and spastic paraparesis. His plasma VLCFA levels, ratios of C24:0/C22:0 and C26:0/C22:0 were all significantly elevated. We performed mutation analysis of the ABCD1 gene in the proband and the family members using direct DNA sequencing and restriction analysis. A novel insertion 496_497insG in exon 1 causing a frame shift and a premature stop codon at amino acid position 194 (D194X) was identified (GenBank accession No. NM_000033). The insertional mutation abolishes an HhaI restriction site. The same mutation was found in his mother and the eldest sister even though their clinical and biochemical abnormalities were milder. Diagnosis of XALD often relies upon the detection of elevated VLCFA levels and ratios of C26:0/C22:0 and C24:0/C22:0 in fasting blood, however, 5–15% of the obligate heterozygotes would give normal values. DNA-based testing thus remains the most reliable tool for heterozygote detection when the disease-causing mutations are known. Using restriction fragment length polymorphism with HhaI, we have devised a rapid method for the identification of the carriers among the proband’s family members and possibly for the screening of the mutations in other XALD patients.
Are Single Nucleotide Polymorphisms of the Immunoglobulin A Fc Receptor Gene Associated with Allergic Asthma?
Authors: Jasek Monika , Obojski Andrzej , Mańczak Maria , Wiśniewski Andrzej , Winiarska Beata , Małolepszy Józef , Jutel Marek , Łuszczek Wioleta , Kuśnierczyk Piotr
Published: December 2004

Background: Eosinophils are important components of allergic inflammation. The immunoglobulin A (IgA) Fc receptor (FcαRI), encoded by the FCAR gene, is a possible candidate for eosinophil activation at mucosal surfaces, where IgA is abundant. Both elevated cell surface expression of FcαRI and increased avidity for IgA were described on eosinophils from allergic subjects. The aim of our study was to examine the possible association of FCAR gene polymorphisms with allergic asthma. Methods: We screened three regions of the FCAR gene: (1) the promoter region, (2) exon 3, encoding the first extracellular domain (EC1), and (3) exon 5, coding for the transmembrane and cytoplasmic domain, for new and published polymorphisms using a sensitive temperature gradient gel electrophoresis technique and compared their frequencies in 112 patients diagnosed with allergic asthma and 100 healthy controls. Results: Six polymorphisms, including two novel ones, were detected. No differences between patients and controls were found in the distribution of any of these polymorphisms. Conclusion: FcαRI polymorphism does not seem to be a risk factor in allergic asthma. Nevertheless, this is the first report on the distribution of 6 single nucleotide polymorphisms of the FCAR gene in a human population and the first study on FCAR polymorphism in allergic asthma.