bluuebunny/crossref_metadata_2025 huggingface dataset:
What Can We Learn from Herceptin® Trials in Metastatic Breast Cancer?
Authors: Bell Richard
Published: April 2003

Herceptin® (trastuzumab), an anti-HER2 monoclonal antibody, is the first oncogene-targeted therapy to be developed for the treatment of metastatic breast cancer. The Herceptin clinical trial program has demonstrated that treatment with Herceptin provides substantial clinical benefits when used either as monotherapy or in combination with a number of chemotherapeutic agents. Of note, accurate assessment of HER2 status is essential to ensure that the patients most likely to benefit from Herceptin are identified: patients with immunohistochemistry (IHC) 3+ or fluorescence in-situ hybridization (FISH)-positive disease gain the greatest clinical benefits. In addition, clinical benefits appear to be greater the earlier Herceptin is used, although there is currently no direct clinical evidence to indicate whether an initial strategy of combination therapy is better than monotherapy or vice versa. Herceptin has been shown to be generally well tolerated. The most severe adverse events are rare serious infusion-related reactions and cardiotoxicity. These adverse events can be managed by standard care and patients at risk can often be identified prior to the initiation of Herceptin treatment. Currently, Herceptin should be given until disease progression, but there could be benefit in continuing treatment beyond disease progression.
Moving Forward: Herceptin® in the Adjuvant Setting
Authors: Tan-Chiu Elizabeth , Piccart Martine
Published: April 2003

HER2 overexpression/amplification, which is an early event in breast cancer development, is associated with a poor prognosis and may predict response to therapy. Herceptin®, an anti-HER2 monoclonal antibody, has shown significant efficacy in the treatment of HER2-positive metastatic breast cancer and appears to provide greater benefit the earlier the drug is given. Moreover, Herceptin also demonstrates a favorable safety profile and is associated with quality-of-life benefits. Taken together, these factors provide the rationale for moving this drug into the adjuvant setting, and four large-scale trials that will involve a total of more than 12,000 women with HER2-positive primary breast cancer have been undertaken to address this issue. In the United States, NSABP trial B31 and the Intergroup N9831 trial will investigate Herceptin in combination with the standard US regimen of anthracycline/cyclophosphamide followed by paclitaxel. Trial BCIRG 006, which is being conducted globally, will examine Herceptin in combination with platinum salts/docetaxel. The HERA Trial, involving countries outside the US, will examine q3-weekly Herceptin monotherapy given for 1 and 2 years after the completion of adjuvant chemo-/radiation therapy. The breadth of the ongoing Herceptin adjuvant trials will potentially allow the optimal treatment approach to be identified.
Prediction of Response to Hormonal Treatment in Metastatic Breast Cancer
Authors: Schmid P. , Wischnewsky M.B. , Sezer O. , Böhm R. , Possinger K.
Published: April 2003

Prediction of outcome and individualization of therapeutic strategies are challenging problems in oncology. Predictive parameters for response to hormonal treatment include the expression of hormone receptor, the extent and location of metastatic spread, disease-free interval, patient age, response to prior hormonal therapy, grading, and more recently, some molecular markers like the expression of HER-2/neu. The use of conventional statistics for prediction of response to hormonal treatment is limited by non-linearities and complex interactions between predictive factors. Modern computational mathematical models like artificial neural networks, entropy-based inductive algorithms or χ2 interaction detection algorithms can describe these interactions and generate classification models and decision structures. They can be used to predict the clinical outcome for individual patients. In contrast to conventional methods, the level of confidence for the predictions can reach 90% and more. This might be an important step towards further individualization of therapeutic strategies.
Multidisciplinary Approach in Advanced Cancer of the Oral Cavity: Outcome with Neoadjuvant Chemotherapy according to Intention-to-Treat Local Therapy
Authors: Grau Juan J. , Domingo Josep , Blanch José L. , Verger Eugenia , Castro Vicente , Nadal Alfons , Alós Llusia , Estapé Jordi
Published: April 2003

Objectives: To determine outcomes in local-regional control and overall survival in patients with squamous locally advanced cancer of the oral cavity, based on intention-to-treat with neoadjuvant chemotherapy followed by surgery or radiation therapy. Methods: Two hundred and four out of 1,089 patients analyzed met the defined criteria. All had squamous cell carcinomas of the oral cavity in stage III or in nonmetastatic stage IV and were selected for surgery or radiation therapy (if located in the tonsils or in the base of the tongue). Chemotherapy was based on cisplatin 120 mg/m2 i.v. day 1 plus bleomycin 20 mg/m2 days 1–5 in continuous i.v. perfusion or plus 5-fluorouracil 1,000 mg/m2 days 1–5 in continuous i.v. perfusion. A total of 418 cycles were given to 204 patients (mean 2.049 per patient). Definitive surgery (n = 73; plus adjuvant radiation therapy) or definitive radiation therapy (n = 131) was performed. Results: One hundred thirty-five out of 204 (66%) patients were chemotherapy responders, 16% complete and 50% partial. One hundred ninety-four patients (95%) completed 2 courses of chemotherapy. After neoadjuvant chemotherapy, 34 out of 46 patients considered inoperable initially (74%) obtained a disease-free status with surgery. Eighty-three percent of surgical patients obtained a disease-free status (initial tumor control) versus 72% of radiation therapy patients. Disease-free survival rates at 5 years were 26 and 22%, respectively. A better prognosis was observed in stage III over IV (p = 0.02); primary tumor in the retromolar trigone, palate or buccal mucosa over tongue, tonsil or floor of the mouth (p = 0.0085); negative cervical nodes over positive (p = 0.0186); responders to chemotherapy over nonresponders (p = 0.0003); and adjuvant postsurgical radiation therapy (p = 0.0013). Causes of death were relapses in local area (86%), regional nodes (10.5%) or distant metastases (3.5%). Eleven patients (5%) died of a second primary. The main toxic effects were vomiting in 9% of patients and hemolytic-uremic syndrome in 3% of the patients treated with bleomycin. Conclusions: In locally advanced squamous cell carcinoma of the oral cavity, neoadjuvant chemotherapy induces a high response rate that may facilitate definitive surgery or radiotherapy. In this study, patients have an acceptable long-term survival.
Characterisation and Assay of Five Enzymatic Activities in the Stratum Corneum Using Tape-Strippings
Authors: Redoules Daniel , Tarroux Roger , Assalit Marie France , Perié Jean Jacques
Published: April 2003

The report describes a method for the assay of five enzymatic activities involved in establishing the stratum corneum permeability barrier: β-glucocerebrosidase, acid phosphatase, phospholipase A2 (PLA2) and two serine proteases: chymotrypsin and its activator in the stratum corneum, trypsin. The specific activities of these different enzymes have been determined along with their pH profiles and sensivities to specific inhibitors. It can be noted that only two presented a pH optimum similar to the pH of the stratum corneum. This could suggest that their activities are regulated by local variations in pH. The method was applied to a pathological situation, that of a non-eczematous dry atopic dermatitis. Atopic skin had significantly reduced trypsin activity, increased acid phosphatase and no change in the activities of three other studied enzymes. Understanding these activities can provide a tool for the characterization of skin pathologies and for the development of a certain number of applications in cosmetology and therapeutics.
Nicotine-Enhanced Epithelial Differentiation in Reconstructed Human Oral Mucosa in vitro
Authors: Kwon Oh Sang , Chung Jin Ho , Cho Kwang Hyun , Suh Dae Hun , Park Kyoung Chan , Kim Kwang Hyun , Eun Hee Chul
Published: April 2003

Oral mucosal keratinocytes represent the cells that first encounter tobacco components. Therefore, tobacco-induced abnormal alteration of the mucosal keratinocytes may contribute to the development of oral white lesions. Nicotine is an ingredient of all tobacco products and pharmacologically the most active component of tobacco smoke. To clarify the effects of nicotine on the keratinization of oral mucosal and epidermal keratinocytes, we reconstructed artificial buccal mucosal and skin equivalents using keratinocytes and fibroblasts from noncornifying buccal mucosa and adult foreskin, respectively. The effect of nicotine on keratinization was assessed with morphology, immunohistochemistry and immunoblotting. Long-term treatment with nicotine for 2 weeks enhanced in a dose-dependent manner the expression of differentiation-specific proteins of oral mucosal keratinocytes on living oral mucosal equivalent and epidermal keratinocytes on living skin equivalent, respectively. The effect of nicotine on the cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Oral mucosal keratinocytes showed a higher resistance to nicotine toxicity than epidermal keratinocytes. Our results suggest that nicotine stimulates differentiation of both mucosal and epidermal keratinocytes, and this nicotine-induced abnormal differentiation may be associated with the development of oral white lesions.
The Effect of Liposomes on Skin Barrier Structure
Authors: Coderch L. , de Pera M. , Perez-Cullell N. , Estelrich J. , de la Maza A. , Parra J.L.
Published: April 2003

The present work deals with the ‘in vivo’ stripping technique to evaluate the percutaneous absorption of sodium fluorescein (NaFl) vehiculized in two different liposome preparations formed by phosphatidylcholine (PC) and lipids mimicking the stratum corneum (SC; ceramides, cholesterol, palmitic acid and cholesteryl sulphate), respectively. Furthermore, the possible effect of these vesicles on the SC lipid alkyl chain conformational order were evaluated at different depths of SC by non-invasive biophysical techniques: Corneometer, Tewameter and especially ATR-FTIR. The results of NaFl percutaneous absorption indicate the highest penetration in the case of incorporation in PC liposomes, which could be related to the increase in SC lipid disorder detected by ATR-FTIR, i.e. a decrease in skin barrier function. On the other hand, SC lipid liposomes have been shown to have a higher affinity for SC owing to the high amount of NaFl found in this layer, suggesting a greater reservoir capacity of SC when similar lipid composition formulation is applied. A lipid order increase is observed by infrared spectroscopy, when these types of liposomes are topically applied, resulting in a strong barrier effect. These results could be useful in designing specific liposomal topical applications.
Influence of Ion Channel Blockers on Proliferation and Free Intracellular Ca2+ Concentration of Human Keratinocytes
Authors: Wohlrab David , Markwardt Fritz
Published: April 2003

The proliferation of in vitro cultivated keratinocytes from the HaCaT cell line while under the influence of different ion channel blockers, i.e. calcium channel blockers tetraethylammonium (TEA) and the nonspecific anion channel blocker 4′,4′-diisothiocyanato-stilbene-2-2′ disulfonic acid (DIDS) was investigated. There were changes in proliferation of the keratinocytes brought on by TEA and DIDS. It can be assumed that the effects of TEA on proliferated keratinocytes lead to a temporary arrest of cells in the G1-phase of the cell cycle. The change in the extracellular K+ concentration ([K+]e) had no influence on the proliferation of keratinocytes. During the entire course of investigations, the adding of DIDS leads to an increase in proliferation. Proliferation of keratinocytes is known to be greatly dependent on intracellular Ca2+ content ([Ca2+]i). The blocking of ion channels with TEA or DIDS does not lead to a change in the free [Ca2+]i. Also a change in the [K+]e does not lead to a displacement of the [Ca2+]i of keratinocytes.
The Role of the Subplate Zone in the Structural Plasticity of the Developing Human Cerebral Cortex
Authors: Kostović Ivica , Judaš Miloš
Published: April 2003

Background: Perinatal lesions of the human brain are followed by a variable extent of functional plasticity and recovery of neurological and cognitive functions. In trying to determine the structural basis of that plasticity, previous studies proposed an essential role for the neuronal elements of the subplate zone. Aim: The purpose of this review is to identify essential features of the subplate zone which represent a developmental potential significant for the areal, axonal, modular and synaptic plasticity of the cerebral cortex, with special emphasis on long ‘waiting’ axonal pathways of the subplate zone. Results: The following features of the subplate zone were found to be essential for its role in the structural plasticity of the human cerebral cortex after periventricular lesions: (1) the presence of waiting fibres; (2) early areal accumulation of thalamocortical afferents; (3) early tangential compartmentalization of neuronal elements; (4) the abundance of extracellular matrix and growth-promoting molecules; (5) the presence of early maturing neurons, neurotransmitters and synapses; (6) differential cell death, and (7) a specific response to hypoxia or perfusion failure. The crucial period for the participation of thalamocortical afferents in the areal and laminar reconstruction is around 24/26 postovulatory weeks (W). For corticocortical callosal and long associative pathways, the critical period is around 34 W and lesions of these fibres can probably cause changes in the formation of gyri, especially around ventriculomegalic and porencephalic regions. It is essential that the subplate zone as well as major related axonal bundles can be visualized in the human cerebrum by the MRI technique. Conclusions: ‘Waiting’ fibres and transient cells of the subplate zone participate in areal, laminar, gyral, axonal, modular and synaptic rearrangements after perinatal lesion in the preterm infant and set limits for the structural plasticity between 22 and 34 W.
Is Endometriosis Really Associated with Pain?
Authors: Momoeda Mikio , Taketani Yuji , Terakawa Naoki , Hoshiai Hiroshi , Tanaka Kenichi , Tsutsumi Osamu , Osuga Yutaka , Maruyama Masanori , Harada Tasuku , Obata Koushirou , Hayashi Kunihiko
Published: April 2003

To address the contrasting findings regarding how pain is related to endometriosis, the relationship between pain and stage of endometriosis was dissected differently by the chief complaint to eliminate selection biases. A total of 1,092 women with endometriosis were classified into two groups depending on their chief complaint, i.e., infertility (infertility group; n = 476) or pain (pain group; n = 616). The correlations between disease stage and various types of pain were analyzed differently in each group. The frequencies of chronic pelvic pain and dyspareunia increased with disease stage either in the infertility group, in the pain group or in the aggregate. On the other hand, no significant relation between the severity of dysmenorrhea and disease stage was observed in the aggregate. Interestingly, a parallel increase in the severity of dysmenorrhea with disease stage was observed in the infertility group, but not in the pain group. In view of selection biases involved in analyzing endometriosis associated with pain, these results could be seen to support the contention that chronic pelvic pain, dyspareunia and dysmenorrhea are in fact related to the extent of endometriosis.
Restrictive Left Ventricular Filling Pattern with Preserved Systolic Function Assessed by Doppler Echocardiography: Clinical, Echocardiographic and Prognostic Implications
Authors: Boccalandro Fernando , Loghin Catalin , Darwood Susan , Seung-Ho Kang , Barasch Eddy
Published: April 2003

From an echocardiographic laboratory database, echocardiographic characteristics of clinical and cardiovascular mortality were compared in patients with restrictive pattern of left ventricular filling (RPLVF) and left ventricular ejection fraction (LVEF) >50% (n = 36), with patients with RPLVF and LVEF <50% (n = 120) and echocardiographic controls (n = 160). Preserved LVEF was found in 21% of the patients with RPLVF. Mortality in patients with RPLVF was worst compared with echocardiographic controls regardless of their underlying LVEF after 2.7 ± 1 years of follow-up. Patients with RPLVF had distinctive predictors of cardiovascular death, with clinical and echocardiographic characteristics according to their LVEF.
Immunoadsorption and Plasma Exchange in Pregnancy
Authors: Dittrich Elisabeth , Schmaldienst Sabine , Langer Martin , Jansen Martin , Hörl Walter H. , Derfler Kurt
Published: April 2003

Background: During pregnancy, familial hyperlipidemia or systemic lupus erythematosus (SLE) can exacerbate having devastating consequences for both mother and fetus. Immunoadsorption is established for removal of pathogenic proteins lipoproteins or autoantibodies, but this procedure has only rarely been used in pregnancy. Methods: We evaluated retrospectively 126 extracorporeal treatments during six pregnancies. Forty low-density lipoprotein immunoadsorptions, 6 sole plasma exchanges and 36 combined procedures (plasma exchange followed by immunoadsorption) were performed for severe hypertriglyceridemia, complicated by acute pancreatitis. Forty-four IgG immunoadsorptions were executed in 2 pregnant women suffering from SLE with a disastrous course during prior pregnancies. Results: In hyperlipidemic pregnant women, mean triglyceride levels prior to treatment were 3,841 ± 2,076 mg/dl (mean ± SD) and total cholesterol was 617 ± 354 mg/dl. Until delivery, a 27% reduction of triglycerides could be achieved. Clinical and serological signs of pancreatitis disappeared after initiation of extracorporeal therapy. Four healthy babies were delivered (birthweights between 2,250 and 3,360 g). In 1 woman suffering from SLE, intrauterine fetal death occurred in the 22nd week of gestation despite a reduction of cardiolipin antibodies by 69%. The second case (a twin pregnancy) was complicated by steroid-resistant antibody-mediated anemia. Due to frequent immunoadsorptions, red blood cell count improved (reduction of antierythrocyte antibodies by 66.6%) and 2 healthy babies (birthweights 2,120 and 2,350 g) were delivered by cesarean section. Conclusion: Long-term antibody-based immunoadsorption has been demonstrated to be safe and well tolerated in pregnant women and enables normal intrauterine/fetal development. Although rarely indicated during pregnancy, this treatment modality might be a promising new technique for removal of autoantibodies and lipoproteins in patients with serious gestational complications without sufficient response to conventional therapy.
Prenatal Evaluation of Bidirectional Epignathus: Comparison of Ultrasonography and Magnetic Resonance Imaging
Authors: Takeuchi Kyousuke , Masuda Yukiko , Narita Fukuko , Kiyoshi Kenji , Mizutori Masakazu , Maruo Takeshi
Published: April 2003

Epignathus is an unusual, benign, congenital teratoma of the hard palate. Most of these teratomas are unidirectional and protrude through the mouth. Hence, the prognosis depends on the size of the tumor and degree of face distortion and airway obstruction. Occasionally, intracranial extension of the tumor is present, involving and destroying the brain tissue, resulting in a poor prognosis. The authors describe 2 cases of bidirectional epignathus, showing the different findings on ultrasonography and magnetic resonance imaging.
Giant Fetal Hepatic Hemangioma
Authors: Pott Bärtsch Eva M. , Paek Bettina W. , Yoshizawa Jyoji , Goldstein Ruth B. , Ferrell Linda D. , Coakley Fergus V. , Harrison Michael R. , Albanese Craig T.
Published: April 2003

The purpose of this case report is to demonstrate the importance of prenatal imaging for treatment management of fetal giant hepatic hemangiomas. Prenatal ultrasound revealed an abdominal mass with several cystic areas and punctate calcifications in a fetus at 29 weeks’ gestation. Doppler scans confirmed the highly vascular nature of the mass. In this case, ultrasound diagnosed the mass was of hepatic origin, while magnetic resonance imaging at 32 weeks’ gestation was more equivocal with respect to the anatomy source of the lesion. Imminent hydrops caused by a rapidly enlarged liver tumor was sonographically demonstrated at 34 weeks’ gestation. An elective C-section and immediate tumor resection was performed. At the age of 20 months the infant is thriving. This case supports the notion that the survival rates for giant hepatic hemangiomas improve when fetal hydrops is averted and specific pre- and postnatal treatment is applied based on correct prenatal imaging diagnostics.
Association between -1438G/A Promoter Polymorphism in the 5-HT2A Receptor Gene and Fluvoxamine Response in Japanese Patients with Major Depressive Disorder
Authors: Sato Kazuhiro , Yoshida Keizo , Takahashi Hitoshi , Ito Kenichi , Kamata Mitsuhiro , Higuchi Hisashi , Shimizu Tetsuo , Itoh Kunihiko , Inoue Kazuyuki , Tezuka Takehiko , Suzuki Toshio , Ohkubo Tadashi , Sugawara Kazunobu , Otani Koichi
Published: April 2003

Genetic polymorphism of the serotonin 5-HT2A receptor seems to be associated with therapeutic response to selective serotonin reuptake inhibitors (SSRIs). The present study investigated whether a novel –1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene is associated with therapeutic response to fluvoxamine (an SSRI) in 66 Japanese patients with major depressive disorder. Fluvoxamine (50 to 200 mg) was administered twice daily for 6 weeks. Fifty-four patients completed this study. The genotype distribution and the allele frequencies showed no significant difference between responders and non-responders. The time-course of the Montgomery-Åsberg Depression Rating Scale scores showed no significant difference among –1438G/G, –1438G/A, and –1438A/A genotype groups. The results demonstrated that the –1438G/A promoter polymorphism in the 5-HT2A receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.
Diet, Breakfast, and Academic Performance in Children
Authors: Kleinman R.E. , Hall S. , Green H. , Korzec-Ramirez D. , Patton K. , Pagano M.E. , Murphy J.M.
Published: April 2003

Objective: To determine whether nutrient intake and academic and psychosocial functioning improve after the start of a universal-free school breakfast program (USBP). Methods: Information was gathered from 97 inner city students prior to the start of a USBP and again after the program had been in place for 6 months. Students who had total energy intakes of <50% of the recommended daily allowance (RDA) and/or 2 or more micronutrients of <50% of RDA were considered to be at nutritional risk. Results: Prior to the USBP, 33% of all study children were classified as being at nutritional risk. Children who were at nutritional risk had significantly poorer attendance, punctuality, and grades at school, more behavior problems, and were less likely to eat breakfast at school than children who were not at nutritional risk. Six months after the start of the free school breakfast programs, students who decreased their nutritional risk showed significantly greater: improvements in attendance and school breakfast participation, decreases in hunger, and improvements in math grades and behavior than children who did not decrease their nutritional risk. Conclusion: Participation in a school breakfast program enhanced daily nutrient intake and improvements in nutrient intake were associated with significant improvements in student academic performance and psychosocial functioning and decreases in hunger.
Insulin Resistance, Impaired Postprandial Lipid Metabolism and Abdominal Obesity
Authors: Frayn Keith N.
Published: April 2003

Objective: To review three ‘emerging risk factors’ for coronary heart disease, the physiological and pathophysiological mechanisms involved, and their inter-relationships. Background: Classical risk factors for coronary heart disease cannot adequately explain the high incidence of this disease. Abdominal obesity and impaired postprandial lipid metabolism have long been recognised as associates of coronary heart disease but only relatively recently has their importance as risk markers been established. Insulin resistance is now often seen as a common theme underlying many factors predisposing to coronary heart disease (CHD). Mechanisms: The mechanisms by which each of these markers relates to coronary heart disease may have common aspects. Specifically, they are all associated with a characteristic dyslipidaemia involving elevation of plasma triacylglycerol concentrations, reduction of high-density lipoprotein cholesterol (HDL-cholesterol) and the presence of small, dense low-density lipoprotein particles that may carry particular risk of atherogenesis. Insulin resistance is also associated with hypertension and impairment of endothelial function, and with a procoagulant state. Treatment: No specific or separate pharmacological treatment of any of these conditions separately has been shown to reduce the risk of CHD although each can be manipulated. Lifestyle modification, with increased physical activity and dietary change, may offer the best hope of primary prevention but to achieve this, interventions at government level rather than advice from individual physicians would probably be required. Conclusions: Abdominal obesity, impaired postprandial lipid metabolism and insulin resistance are all inter-related risk markers for CHD. They seem to reflect lifestyle in the developed and developing worlds and perhaps modification of lifestyle holds the greatest hope for their amelioration in the future.
Long-Term Suppression of Pituitary-Gonadal Function with Three-Month Depot of Leuprorelin Acetate in a Girl with Central Precocious Puberty
Authors: Schroeter Manuela , Baus Inka , Sippell Wolfgang G. , Partsch Carl-Joachim
Published: April 2003

Objective: The efficacy of a 3-month depot preparation of the GnRH agonist leuprorelin acetate in central precocious puberty was studied. Methods: Treatment with a 3-month depot of leuprorelin acetate was performed subcutaneously in a 7.3-year-old girl with central precocious puberty. Results: During treatment the hormonal suppression was constant and complete as demonstrated by suppressed GnRH stimulation tests and prepubertal estradiol plasma levels. The size and volume of the uterus and ovaries returned to the normal range. The rate of bone maturation was significantly reduced with a ratio ΔBA/ΔCA of 0.58 for 3 treatment years. Thus, the effects of treatment were comparable to those reported for treatment with 1-month depot of GnRH agonists. Conclusion: Three-month depots have the advantage of a prolonged injection interval which is more convenient for the patients and reduces costs by necessitating fewer visits to the physician and being approximately 10% cheaper than the 1-month depot. We suggest that comparative and randomized studies be performed to make 3-month depots of GnRH agonists available for routine use in children with central precocious puberty.
Change in Generic and Disease-Specific Health-Related Quality of Life during a One-Year Period in Patients with Newly Detected Chronic Obstructive Pulmonary Disease
Authors: Tsukino Mitsuhiro , Nishimura Koichi , McKenna Stephen P. , Ikeda Akihiko , Hajiro Takashi , Zhang Min , Izumi Takateru
Published: April 2003

Background: Although the health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD) has been assessed by generic or disease-specific HRQoL measures, the responsiveness of the generic HRQoL measures is generally weak. Objectives: To investigate the responses generated by generic and disease-specific HRQoL questionnaires, we prospectively followed the clinical course of patients with newly detected COPD after the initiation of treatment. Methods: A prospective, longitudinal study with a 1-year follow-up was designed. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), the Nottingham Health Profile (NHP) as a generic HRQoL measure, and the Chronic Respiratory Disease Questionnaire (CRQ) as a disease-specific HRQoL measure were measured at baseline and at 3, 6, and 12 months after the initiation of standard treatment. Results: Eighty-two patients completed the study. The FEV1, FVC, and NHP and CRQ scores improved significantly during the first 3 months (p < 0.05). During the last 6 months, although the FEV1 declined (p < 0.05), the HRQoL assessed by the NHP and CRQ remained elevated. Except for the score on the social isolation section of the NHP at 12 months, all HRQoL scores at 6 and 12 months were significantly improved compared to baseline (p < 0.05). Conclusion: In new patients with COPD, the NHP as well as the CRQ was able to detect changes in the HRQoL associated with effective medical interventions. The influence of the changes in airflow limitation on the HRQoL was weak.
Abnormalities on Cardiopulmonary Exercise Test in a Dyspneic Patient
Authors: Bhagat Rajesh , Schreiber Gilbert
Published: April 2003

The cardiopulmonary exercise test (CPET) is frequently used for the quantitative evaluation of exercise tolerance and for the qualitative assessment of the origin of dyspnea. Although reasonably safe, CPET is contraindicated in acute clinical situations and relatively contraindicated in severe pulmonary hypertension. Pulmonary emboli are usually present during the acute onset of pulmonary hypertension; however, in situations where pulmonary vascular disease is more unsuspected, CPET may help with the diagnosis. We present a report of a 47-year-old Caucasian female with a 2-month history of exertional dyspnea. She had a normal pulmonary function test, arterial blood gas analysis and CT scan of the chest. On CPET she was found to have a higher than normal physiological dead space to tidal volume ratio, increased ventilatory equivalent for the elimination of CO2 (VE/VCO2), persistently positive arterial-end-tidal PCO2 difference at peak exercise, and a low anaerobic threshold suggestive of pulmonary vascular disease. She was subsequently diagnosed with pulmonary embolic disease by her ventilation/perfusion scan and pulmonary arteriogram. This report highlights the importance of recognizing the hallmarks of unsuspected pulmonary vascular disease on CPET.
Mycobacterium avium Complex Pleuritis
Authors: Yanagihara Katsunori , Tomono Kazunori , Sawai Toyomitsu , Miyazaki Yoshitsugu , Hirakata Yoichi , Kadota Jun-Ichi , Kohno Shigeru
Published: April 2003

Non-tuberculous mycobacterium infection is rarely accompanied by pleural involvement. We report a very rare case of Mycobacterium avium-intracellurare complex (MAC) pleuritis with massive pleural effusion. The patient was a non-compromised 67-year-old female and had been treated for pulmonary non-tuberculous mycobacterium infection. She was admitted to hospital because of general malaise, low-grade fever and right pleural effusion. Cytological examination of the effusion did not show malignant cells. MAC was only identified by culture and PCR. No other bacteria were detected. Complete resolution of the pleural effusion occurred after administration of anti-tubercular agents (isoniazid, rifampin, ethambutol) and clarithromycin.
Smoking Reduction for Smokers Not Able or Motivated to Quit?
Authors: Tønnesen Philip
Published: April 2003

Smoking reduction, i.e. a sustained decrease in the number of cigarettes smoked daily, is a highly controversial area. Results from population studies are reported as well as from the few randomized controlled studies published. The effect with regard to smoking reduction seems small and there is only limited evidence that smoking reduction is followed by improvement in some health-related parameters. More biomarkers of smoking reduction need to be examined specially with regard to carcinogenic biomarkers. Smoking reduction seems to be of interest for smokers not motivated or able to quit, as a small percent of this group quit smoking during reduction trials. Further research is needed to evaluate the value of this concept. However, smoking cessation is still the ultimate goal.
US Experience in Evaluation and Diagnosis of GH Therapy of Intrauterine Growth Retardation/Small-for-Gestational-Age Children
Authors: Saenger Paul
Published: April 2003

The potential role of exogenous GH in treating short children born small for gestational age (SGA) has been discussed since the early 1960s. Pivotal studies in Europe during the last 10 years have shown that GH treatment of short children born SGA during childhood and early puberty (1) normalizes stature, (2) increases final height above predicted height and (3) allows children to reach their target height. A study now under way in the USA will provide additional much needed data about efficacy and safety of GH treatment in intrauterine growth retardation/SGA.
Osteoporosis and the Growth Hormone-Insulin-Like Growth Factor Axis
Authors: Geusens Piet P.M.M , Boonen Steven
Published: April 2003

Osteoporosis is the result of an imbalance between bone resorption and bone formation. Currently, mainly drugs that inhibit bone resorption are available for the treatment of osteoporosis. A new approach in the treatment of osteoporosis is the use of anabolic agents that increase bone turnover, both bone formation and resorption. Growth hormone (GH) and insulin-like growth factors (IGFs) are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. We will review the evidence of GH and IGF-I in the pathophysiology and treatment of osteoporosis.
Risk of Mortality in Patients with End-Stage Renal Disease: The Role of Malnutrition and Possible Therapeutic Implications
Authors: Zeier M.
Published: April 2003

The mortality rate of dialysis patients is still considerably high. Beside the traditional risk factors, specific uremia-related risk factors are identified. Among them, hypoalbuminemia and malnutrition have a strong association to mortality in chronic dialysis patients. Various studies document a strong relation between reduced calorie and protein uptake and mortality in uremic patients. Several factors responsible for malnutrition in dialysis patients have been identified. These factors may be dialysis-associated, due to intercurrent illnesses or are associated with uremic complications (e.g. hyperparathyroidism, anemia, acidosis, etc.). Malnutrition is treatable and can be avoided by several means. Beside the increase in the dose of dialysis and adequate protein and calorie intake, intradialytic nutrition is an additional choice. The combination with specific drugs (e.g. growth hormone) may potentiate the success of the modified treatment modalities, particularly in patients who need nutritional support during an intercurrent illness. Further studies are required to measure the impact of for example growth hormone supplementation on mortality rate and quality of life in malnourished patients on chronic dialysis.
Growth Hormone Secretagogues and Ghrelin: An Update on Physiology and Clinical Relevance
Authors: Petersenn S.
Published: April 2003

The pulsatile release of growth hormone (GH) by the anterior pituitary is stimulated by small synthetic molecules termed GH secretagogues (GHS). The receptor for GHS (GHS-R) belongs to the family of G-protein-coupled receptors. An endogenous specific ligand of 28 amino acids has recently been purified from rat stomach, it has been termed ‘ghrelin’. Ghrelin demonstrates potent and reproducible GH-releasing activity, as well as significant prolactin-, ACTH- and cortisol-releasing activity. However, its major physiological relevance may relate to energy homeostasis. Peripheral daily administration of ghrelin caused weight gain by reducing fat utilization in mice and rats. In man, intravenous ghrelin was shown to stimulate food intake. The pathophysiological role and the potential clinical use of ghrelin are reviewed.
Mortality and Morbidity in Nonagenarian Patients following Hip Fracture Surgery
Authors: Formiga F. , Lopez-Soto A. , Sacanella E. , Coscojuela A. , Suso S. , Pujol R.
Published: April 2003

Background: The number of people living more than 90 years is increasing, and this population shows a high incidence of hip fractures. Objective: To study prospectively the mortality and morbidity following hip fracture surgery in nonagenarian patients. Methods and Subjects: 106 nonagenarian patients were admitted for femoral neck fracture and treated surgically in the traumatology and geriatric departments of two university hospitals. All patients received comprehensive geriatric assessment. 75 patients were followed up after a 3-month control period. Mortality and functional status were assessed using the Barthel index (BI) and mobility, dependency on walking aids, residential status, and degree of residual pain were the items assessed for morbidity. Results: In-hospital mortality was 10%; the 3-month accumulate mortality was 20%. The mean BI of the 75 patients who survived was 53 showing a persistent decrease compared with their BI previous to the hip fracture (79; p < 0.003). The decline in BI after 3 months persisted in 91% of patients. Before injury, 11% patients were housebound, while 45% were housebound 3 months later. 54% were independent before the fracture occurred, and only 16% 3 months later. Only 12% of patients who survived were unable to return to their pre-admission dwelling. Conclusions: Findings of low perioperative mortality and acceptable morbidity support the view that surgery followed by rehabilitation is indicated in selected nonagenarian patients.
Biochemical Markers of Nutrition and Bone Mineral Density in the Elderly
Authors: Di Monaco Marco , Vallero Fulvia , Di Monaco Roberto , Mautino Fulvio , Cavanna Alberto
Published: April 2003

Background: Protein depletion is detrimental in bone health, but the association between bone mineral density (BMD) and serum albumin is controversial. We recently showed a positive association between femur BMD and total lymphocyte count (TLC), a validated marker of protein nutrition status, in hip-fractured women. Objective: To investigate the association between femur BMD and both serum albumin and TLC in hip-fractured men and women. Methods: 286 of 315 hip-fractured patients (243 women and 43 men) consecutively admitted to a rehabilitation hospital were studied. BMD was measured by DXA in the unfractured femur. The correlation between BMD and both TLC and serum albumin was studied by Pearson’s coefficient and Bonferroni adjustment. Results: In women a positive correlation was observed between, TLC but not albumin, and BMD measured in the total femur (r = 0.26; p < 0.01), femur neck (r = 0.21, p < 0.01), trochanter (r = 0.22, p < 0.01), intertrochanteric area (r = 0.25, p < 0.01) and Ward’s triangle (r = 0.17, p < 0.05). Conversely in men a positive correlation was found between albumin, but not TLC, and BMD measured in the total femur (r = 0.50, p < 0.01), femur neck (r = 0.52, p < 0.01), intertrochanteric area (r = 0.52, p < 0.01) and Ward’s triangle (r = 0.49, p < 0.01). Linear multiple regression showed that the associations were independent of age, weight, height, body mass index, erythrocyte sedimentation rate, time between surgery and blood sample collection and type of hip fracture. Conclusion: Our results support the role of protein nutrition in bone health, at least in elderly frail patients. TLC and serum albumin were suitable markers, however sex-related differences in their usefulness were observed.
Desmoplastic Small Round Cell Tumour: A Description of Two Cases and Review of the Literature
Authors: Lippe Paolo , Berardi Rossana , Cappelletti Claudia , Massacesi Cristian , Mattioli Rodolfo , Latini Luciano , Cellerino Riccardo
Published: April 2003

Background: Desmoplastic small round cell tumour (DSRCT) is a recently described neoplasm, typically occurring in adolescent and young males. It usually shows an aggressive behaviour, presents in the abdomen, often with diffuse peritoneal implants. It has been demonstrated to be a chemosensitive tumour, generally with short-lasting response and poor survival gain from systemic chemotherapy. The authors report two additional cases of DSRCT and review the available medical literature. Patients and Methods: Two young males with intra-abdominal DSRCT were treated with a first-line chemotherapy including carboplatin, doxorubicin and etoposide. Results: Both of the patients obtained a partial response after first-line chemotherapy. The first patient started, subsequently, CD34+ stem cell mobilisation with high-dose cyclophosphamide (7 g/m2) in order to perform high-dose chemotherapy, but CD34+ cell count was insufficient to practice leukapheresis; he died 34 months after the diagnosis because of progression of the disease. The second patient underwent cytoreductive surgery, but progressed 2 months later despite second-line treatment; he died 16 months after the diagnosis. Conclusion: This experience confirms that DSRCT may be considered a chemosensitive tumour, highly aggressive, with short-lasting response to chemotherapy. Anyway, the recent literature suggests that multidisciplinary treatment including chemotherapy, surgery and radiation might be the proper approach to this rare malignancy.
Preoperative Serum Alpha-L-Fucosidase Activity as a Prognostic Marker in Colorectal Cancer
Authors: Ayude Daniel , Páez de la Cadena María , Martínez-Zorzano Vicenta S. , Fernández-Briera Almudena , Rodríguez-Berrocal Francisco J.
Published: April 2003

Objectives: The aim of this study was to examine the prognostic value of the preoperative serum α-L-fucosidase (AFU) activity in colorectal cancer and to assess whether it could add prognostic information that Dukes’ stages do not give. Methods: A postoperative follow-up of 137 colorectal cancer patients was performed, and survival analyses were carried out to evaluate the impact of AFU activity on disease-free survival. Dukes’ stage classification, preoperative serum carcinoembryonic antigen levels and six other clinicopathological features of the patients were also analysed. Results: In previous studies, we have stressed the diagnostic value of AFU activity in preoperatively obtained serum from colorectal cancer patients. In the present work, we have found that the enzymatic activity of serum AFU was not related to the Dukes’ stage of the primary tumour, but it was associated with the type of metastasis and recurrence of the disease. The mean value of preoperative serum AFU activity was higher in patients with distant metastases than in those with lymph node or peritoneal metastases, or without metastasis (p = 0.034). After a mean postoperative follow-up period of 22 months, three groups of patients with different recurrence rates could be distinguished (p = 0.0014). Similar results were found when only patients in Dukes’ stage B (p = 0.0439) or C (p = 0.0122) were considered. Conclusions: According to our findings, serum AFU activity appears to be a good prognostic factor of tumour recurrence in colorectal carcinoma. Furthermore, patients in Dukes’ stage B or C at high or very high risk of tumour recurrence could be spotted.
Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2
Authors: Buchet-Poyau K. , Mehenni H. , Radhakrishna U. , Antonarakis S.E.
Published: April 2003

Pathogenic mutations in the serine/threonine kinase STK11 (alias LKB1) cause Peutz-Jeghers syndrome (PJS) in most affected individuals. However, in a considerable number of PJS-patients mutations cannot be detected in STK11 suggesting genetic heterogeneity. One PJS family without STK11 mutations (PJS07) has previously been described with significant evidence for linkage to a second potential PJS locus on 19q13.3→q13.4. In this study we investigated candidate genes within markers D19S180 and D19S254, since multipoint linkage analysis yielded significant LOD scores for this region in this family. Four genes in the region (cytohesin 2: PSCD2, kallikrein 10: KLK10, protein kinase C gamma: PRKCG, and serine/threonine kinase 13: STK13) potentially involved in growth inhibitory pathways or in the pathophysiology of can- cer, were considered as candidates. We first determined the genomic structure of the PSCD2 and PRKCG genes, and performed mutation analysis of all exons and exon-intron junctions of the four genes, in the PJS07 family. No pathogenic mutation was identified in these four genes in affected individuals. A very rare polymorphism resulting in a conserved amino acid change Lys to Arg was found in PSCD2. These data provide considerable evidence for exclusion of these four genes as candidates for the second locus on 19q13.3→q13.4 in PJS. Finally, we also excluded the recently identified STK11-interacting protein gene (STK11IP, alias LIP1) mapped in 2q36 as candidate for PJS in the PJS07 family, although this could be a good candidate in other non-STK11/LKB1 families.
Recognition Memory in Alzheimer’s Disease
Authors: Karlsson Thomas , Johansson Inez , Adolfsson Rolf , Nilsson Lars-Göran , Dubuc Severine
Published: April 2003

A compelling feature of human memory is its striking capacity. Under certain circumstances, subjects can remember large amounts of information even with brief exposure at study. This investigation shows that this ability is preserved even in severely impaired Alzheimer’s disease patients, and this holds implications for the clinical management of amnesic patients. To this date, demonstrations of preserved learning and memory capacity in Alzheimer’s disease and amnesia have been confined to implicit memory tasks. Since the present results were obtained in an explicit memory task, the finding also holds implications for the understanding of amnesia.
The Economics of Alzheimer Disease
Authors: Leung G.M. , Yeung R.Y.T. , Chi I. , Chu L.W.
Published: April 2003

Economic assessments of health and healthcare have become an integral part of policy decisions in the last decade. Increasingly, this trend is extending to medical decision-making in day-to-day patient-provider interactions. Alzheimer disease (AD) offers a potent example of the clinical and economic issues at stake with its diagnostic techniques, pharmacotherapies, and public health and policy implications. This review introduces basic economic concepts in examining the impact of AD and related care. It presents a summary of the latest economics research on cost estimates of AD and on economic evaluations of diagnostic and management interventions in terms of cost-of-illness and cost-effectiveness studies respectively. Empirical and conceptual issues about the interpretation of costs and the uses of evaluative methods are also discussed. We found that the economic costs attributable to AD care is highly variable mostly due to non-standardised methodologies and geographical variations in care patterns. There is, however, little doubt that the impact is substantial and is expected to worsen with the demographic, epidemiologic, technologic and economic transitions worldwide. There are comparatively fewer studies on the cost-effectiveness of interventions in AD. Most of the published work revolves around pharmacotherapeutics while relatively little has been done on diagnostics, patient care programmes and programmes for caregivers. We conclude that there are significant opportunities to strengthen research on standardised cost-of-illness analyses and new cost-effectiveness studies on a broader range of AD interventions.