The determinants of dyspnoea evaluated by the mMRC scale: The French Palomb cohort.

INTRODUCTION AND OBJECTIVE: Dyspnoea is a major symptom in COPD patients, but the determinants that could be associated with a higher dyspnoea mMRC score in COPD patients remain unclear. Our research aimed to study the determinants of dyspnoea at the threshold of 1, 2, 3 and 4 mMRC. PATIENTS AND METHODS: Diagnosis of COPD was made using spirometry with post-bronchodilator FEV1FVC<70%. An online questionnaire has been employed by pulmonologists to recruit COPD patients. The following variables were collected: age, gender, BMI, FEV1, RV, IC, TLC, FRC, mMRC, frequency of exacerbations and comorbidities. The LASSO was used to select the variables associated with the mMRC dyspnoea scale in a subgroup (who had no missing IC, RV and FRC values) of 421 COPD patients defined by the previously mentioned variables. RESULTS: One thousand nine hundred and sevety-three patients (65.3% males, average age=66±10, 38% current smokers) were included. Dyspnoea was correlated with a low FEV1 and with the number of exacerbations in the past 12 months. Multivariate analysis showed that the determinants of dyspnoea(mMRC≥2) are: FEV1: OR=3.71[2.86-4.82]; anxiety: OR=2.52[1.82-3.47]; cough: OR=1.94[1.57-2.40]; bronchiectasis: OR=1.84[1.03-3.29]; age: OR=1.80[1.45-2.24]; hyperinflation (RV/TLC): OR=1.68[1.34-2.11]; ischemic cardiopathy: OR=1.63[1.22-2.18]; hypertension: OR=1.52[1.21-1.91]; exacerbations (≥2): OR=1.41[1.10-1.81]; women: OR=1.39[1.10-1.74] and overweight: OR=1.33[1.06-1.67]. The subgroup analysis showed that: FEV1: OR=3.47[1.96-6.12]; exacerbations (≥2) OR=2.31[1.33-4.17] and hyperinflation (IC/TLC) OR=0.57[0.35-0.85] were associated with higher dyspnoea (mMRC≥2). CONCLUSION: Our results showed that dyspnoea is related to the severity of airflow limitation, gender, exacerbations, comorbidities and hyperinflation.

Lung abscess in a child secondary to Mycoplasma pneumoniae infection.

We present a case of a lung abscess in a child 6-year-old admitted with a history of right hemithorax pain lasting for 15 days and the onset of mild fever in the last two days. Etiological research showed positivity of IgM antibodies to Mycoplasma pneumoniae after seven days of admission. The child has been successfully treated with antibiotic therapy, without the use of macrolides, for a duration of 4 weeks. Our study suggests that the Mycoplasma pneumoniae infection may predispose to severe infections, such as lung abscess, caused by typical respiratory pathogens. The reported case of lung abscess is one of the few reported in the literature in the modern antibiotic era and is the first preceded by Mycoplasma pneumoniae infection.

DNA profiling, telomere analysis and antioxidant properties as tools for monitoring ex situ seed longevity.

BACKGROUND AND AIMS: The germination test currently represents the most used method to assess seed viability in germplasm banks, despite the difficulties caused by the occurrence of seed dormancy. Furthermore, seed longevity can vary considerably across species and populations from different environments, and studies related to the eco-physiological processes underlying such variations are still limited in their depth. The aim of the present work was the identification of reliable molecular markers that might help in monitoring seed deterioration. METHODS: Dry seeds were subjected to artificial ageing and collected at different time points for molecular/biochemical analyses. DNA damage was measured using the RAPD (random amplified polymorphic DNA) approach while the seed antioxidant profile was obtained using both the DPPH (1,1-diphenyl, 2-picrylhydrazyl) assay and the Folin-Ciocalteu reagent method. Electron paramagnetic resonance (EPR) provided profiles of free radicals. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to assess the expression profiles of the antioxidant genes MT2 (type 2 metallothionein) and SOD (superoxide dismutase). A modified QRT-PCR protocol was used to determine telomere length. KEY RESULTS: The RAPD profiles highlighted different capacities of the two Silene species to overcome DNA damage induced by artificial ageing. The antioxidant profiles of dry and rehydrated seeds revealed that the high-altitude taxon Silene acaulis was characterized by a lower antioxidant specific activity. Significant upregulation of the MT2 and SOD genes was observed only in the rehydrated seeds of the low-altitude species. Rehydration resulted in telomere lengthening in both Silene species. CONCLUSIONS: Different seed viability markers have been selected for plant species showing inherent variation of seed longevity. RAPD analysis, quantification of redox activity of non-enzymatic antioxidant compounds and gene expression profiling provide deeper insights to study seed viability during storage. Telomere lengthening is a promising tool to discriminate between short- and long-lived species.

Transient neonatal hyperinsulinemic hypoglycemia and neurological outcome: a case report.

Transient neonatal hyperinsulinemic hypoglycemia (TNHI) is a form of neonatal-onset hyperinsulinism which usually resolves completely in a few days or months. It is secondary to conditions such as maternal diabetes mellitus or intra-uterine growth retardation. Other rare causes of TNHI are perinatal asphyxia and gestational diabetes. Hyperinsulinemic hypoglycemia (HI) is also observed in association with rare metabolic or genetic conditions. It can also occur in newborns without risk factors. TNHI is usually a transient phenomenon. However, some newborns can have prolonged HI that requires treatment with diazoxide, persists for several months and then resolves spontaneously. Neonatal hyperinsulinemic hypoglycemia must be promptly and correctly diagnosed and treated in order to avoid neurological consequences. We describe a case of transient neonatal hyperinsulinemic hypoglycemia in a full-term born without perinatal complications and appropriate for gestational age with an unfavourable neurological outcome.

[Markers of brain injury in non-invasive biological fluids]. / Markers of brain injury in non-invasive biological fluids.

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular autoregulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present article is aimed at investigating the role of dosage biochemical markers in non-invasive biological fluids such as S100B, a calcium binding protein, activin A, a protein expressed in Central nervous System (CNS).

Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood.

Brain-derived neurotrophic factor (BDNF) has been reported to be critical for the development of cortical inhibitory neurons. However, the effect of BDNF on the expression of transcripts whose protein products are involved in gamma amino butric acid (GABA) neurotransmission has not been assessed. In this study, gene expression profiling using oligonucleotide microarrays was performed in prefrontal cortical tissue from mice with inducible deletions of BDNF. Both embryonic and adulthood ablation of BDNF gave rise to many shared transcriptome changes. BDNF appeared to be required to maintain gene expression in the SST-NPY-TAC1 subclass of GABA neurons, although the absence of BDNF did not alter their general phenotype as inhibitory neurons. Furthermore, we observed expression alterations in genes encoding early-immediate genes (ARC, EGR1, EGR2, FOS, DUSP1, DUSP6) and critical cellular signaling systems (CDKN1c, CCND2, CAMK1g, RGS4). These BDNF-dependent gene expression changes may illuminate the biological basis for transcriptome changes observed in certain human brain disorders.

Effects of transforming growth factor-beta on aggrecanase production and proteoglycan degradation by human chondrocytes in vitro.

OBJECTIVE: Aggrecan is degraded by Aggrecanases (ADAMTS-4 and -5) and MMPs, which cleave its core protein at different sites. Transforming growth factor (TGF)beta is known to stimulate matrix formation in cartilage, and ADAMTS-4 production in synoviocytes. The aim of this in-vitro study was to examine the effects of TGFbeta on aggrecanase production in human cartilage. DESIGN: Expression of ADAMTS-4 and -5 in chondrocyte cultures from normal or osteoarthritic cartilage was studied at mRNA level by RT-PCR. Aggrecanase activity was examined by western blot of aggrecanase-generated neoepitope NITEGE, and by measure of proteoglycan degradation in cartilage explants. RESULTS: TGFbeta strongly increased mRNA levels of ADAMTS-4, while ADAMTS-5 was expressed in a constitutive way in chondrocytes from normal and osteoathritic cartilage. TGFbeta also increased NITEGE levels and proteoglycan degradation. Addition of an aggrecanase inhibitor blocked the increase of NITEGE, and partially inhibited proteoglycan degradation. CONCLUSIONS: TGFbeta stimulates ADAMTS-4 expression and aggrecan degradation in cartilage. This catabolic action seems to be partially mediated by aggrecanases. It is, therefore, proposed that the role of TGFbeta in cartilage matrix turnover is not limited to anabolic and anti-catabolic actions, but also extends to selective degradation of matrix components such as aggrecan.

Effects of agonists of peroxisome proliferator-activated receptor gamma on proteoglycan degradation and matrix metalloproteinase production in rat cartilage in vitro.

OBJECTIVE: To examine the effects of agonists of peroxisome proliferator-activated receptor (PPAR) gamma on proteoglycan degradation induced by interleukin (IL)-1beta or tumor necrosis factor (TNF)alpha in cartilage in vitro. DESIGN: Proteoglycan degradation was measured as release of radioactivity from rat cartilage explants previously labeled with (35)SO2-4. Western blots were used to examine tissue levels of aggrecan neoepitopes NITEGE and VDIPEN, generated by aggrecanases and matrix metalloproteinases (MMP), respectively. Production of MMP-2, -3 and -9 by cultured rat chondrocytes was measured by zymography and by fluorimetric assay. RESULTS: IL-1beta-induced proteoglycan degradation was likely due to aggrecanase, since it was associated with a strong increase of NITEGE signal. MMP-dependent VDIPEN signal increased only after further incubation with pro-MMP activator APMA. PPAR agonists 15d-PGJ(2) and GI262570 (10 microM) inhibited IL-1beta- and TNFalpha-induced proteoglycan degradation measured both before and after addition of APMA. The agonists also inhibited cytokine-induced MMP production by isolated chondrocytes. CONCLUSION: This study shows that PPARgamma agonists inhibit cytokine-induced proteoglycan degradation mediated by both aggrecanase and MMP. This effect is associated with inhibition of production of MMP-3 and -9. These results support the interest for PPARgamma agonists as candidate inhibitors of pathological cartilage degradation.

YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes.

YKL-40 (cartilage gp-39), is a mammalian glycoprotein related in sequence to chitinases. Its function is unknown, but it is thought to be involved in tissue remodeling. Immunocytochemical staining of YKL-40 in guinea pig chondrocytes (GPC), rabbit chondrocytes (RC), and rabbit synoviocytes (RS) was higher in dividing cells than in confluent cells, suggesting a participation of YKL-40 in cell cycle events. As assessed by the MTT assay, YKL-40 at 1.9-7.6 nM had dose-dependent mitogenic activity toward the three cell types. At 7.6 nM, YKL-40 increased the number of cells of 42% in GPC, 75% in RC, and 86% in RS after 72 h. YKL-40 also stimulated total proteoglycan synthesis by chondrocytes in a dose-dependent manner as assessed by Na[35SO4] incorporation and cetylpyridinium chloride precipitation. At 9.4 nM, YKL-40 increased proteoglycan synthesis of 42% in GPC and 58% in RC after 24 h. The growth factor properties of YKL-40 may explain the increased tissue remodeling associated with high levels of YKL-40 in joint diseases, and possibly, in malignant pathologies such as breast cancer or colorectal cancer.

Effects of ceramide on aggrecanase activity in rabbit articular cartilage.

Ceramide participates in signal transduction of IL-1 and TNF, two cytokines likely involved in cartilage degradation in osteoarthritis. We previously showed that ceramide stimulates proteoglycan degradation, mRNA expression of matrix metalloproteinase (MMP)-1, -3, and -13, and pro-MMP-3 production in rabbit cartilage. Since aggrecan, the main cartilage proteoglycan, can be cleaved by metalloproteinases both of MMP and aggrecanase type, the aim of this study was to determine if ceramide stimulates aggrecanase action and, if that is the case, in which measure aggrecanase mediates the degradative effect of ceramide. To this end, antibodies were used against the C terminal aggrecan neoepitopes generated by aggrecanases (NITEGE(373)) and MMPs (DIPEN(341)). Ceramide C(2) at 10(-5) to 10(-4) M dose-dependently increased NITEGE signal, without changing that of DIPEN, in cultured explants of rabbit cartilage. The effects of 10(-4) M C(2) on NITEGE signal and proteoglycan degradation were similarly antagonized by the metalloproteinase inhibitor batimastat, with return to the basal level at 10(-6) M. These results show that, similarly to IL-1 and TNF, ceramide-induced aggrecan degradation is mainly due to aggrecanases. That no increase of MMP activity was detected, despite stimulation of MMP expression, was probably due to lack of proenzyme conversion to mature form, since addition of a MMP activator to C(2)-treated cartilage increased both DIPEN signal and proteoglycan degradation. These findings support the hypothesis that cytokine-induced ceramide could play a mediatory role in situations of increased degradation of cartilage matrix.

Contraception. Myths, facts and methods.

OBJECTIVES: After reading this article, the reader should be able to: 1. Recognize the mechanism of action, side effects, contraindications, precautions and instructions for use of a variety of contraceptive methods. 2. Understand the advantages and disadvantages of the various contraceptive methods. 3. List the common myths and misconceptions about conception and contraception, and recognize how they can influence contraceptive decisions. Unintended pregnancy is a serious problem in the United States. Counseling a patient about conception and contraception involves more than simply imparting information and answering questions. Clinicians should actively detect and correct any myths and misapprehensions on the patient's part. These myths are quite common and can interfere with treatment if not attended to. This article summarizes common myths about pregnancy and contraception and reviews the key facts about both.

General synthesis of alpha-substituted 3-bisaryloxy propionic acid derivatives as specific MMP inhibitors.

Modulations of alpha and aryl substitutions on 3-aryloxy propionic acid hydroxamates led to novel and potent inhibitors of MMP-2,3,9 and 13, and selectivity versus MMP-1.

[Significance of ultrasonography in the diagnosis of appendicitis]. / Importanza dell'ultrasonografia nella diagnosi di appendicite.

AIM: The authors aim to evaluate the sensitivity and specificity of abdominal ultrasonography in 183 in-patients (113 females--70 males), aged between 3 and 78 years old, in the General Surgery department of Pugliese Hospital in Catanzaro, for abdominal pain and possible acute appendicitis, using a retrospective study. All patients underwent ultrasonography at the Division of Radiology in the same hospital. METHODS: The technique used was graded-compression US (useful to eliminate gas artifacts and to reduce the distance from the appendix) using a linear transducer between 3.5 and 7.5 MHz. The method lasted an average of 15 minutes and was performed by specially trained radiologists. The transducer was held between the forefinger and thumb and pushed into the abdomen using both palms, as if palpating the abdomen. When compression is applied slowly and gently, the pain is surprisingly well tolerated by the patient. The radiologist records whether the inflamed appendix is visualised ultrasonographically and with what degree of certainty, and whether perforations or the formation of abscesses and other pathological processes can be seen. In this case, clinical diagnosis was confirmed by radiological imaging and eventually by surgical evidence. RESULTS: Of the 183 patients examined, 135 showed positive US findings, 11 refused surgery and pain was resolved by pharmacological treatment, and 9 presented other pathologies (3 gastric ulcers, 4 acute cholecystitis and 2 extrauterine pregnancies). Therefore, 115 patients were effectively positive. Of the 183 patients, 48 were negative but of these, only 39 were effectively negative because 3 were false negatives and 6 revealed other pathologies when examined using other methods of diagnosis. Even if the diagnosis of appendicitis was confirmed by clinical examination in most cases, US is of value both to confirm the clinical diagnosis and to rule out any complications. In this particular case it was also useful for the surgeon as a means of locating the position of the appendix. Even if this method is partly conditioned by the patient's clinical conditions, the results were excellent. CONCLUSIONS: The authors conclude that US of the appendix is a valuable aid in the diagnosis of appendicitis, especially in the case of acute or subacute forms in which other radiological imaging might worsen the pathology and lead to the onset of further complications. US offers undeniable advantages using a non-invasive, low cost technique with a specificity of around 80% and sensitivity between 85 and 93%. It also provides a means of identifying other sources of low abdominal pain. However, we still regard clinical examination as being essential for diagnosis.

Effects of ceramide on apoptosis, proteoglycan degradation, and matrix metalloproteinase expression in rabbit articular cartilage.

Cartilage loss in osteoarthritis is characterized by matrix degradation and chondrocyte death. The lipid messenger ceramide is implicated in signal transduction of the catabolic cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), as well as in apoptosis. The aim of this study was to examine the in vitro effects of ceramide on proteoglycan degradation, matrix-metalloproteinase (MMP) expression and activity, and chondrocyte apoptosis in rabbit articular cartilage. Cell-permeant ceramide C(2) stimulated proteoglycan degradation in cartilage explants starting from 3 x 10(-5) M, with 100% increase at the dose of 10(-4) M. This effect was probably due to MMPs since it was blocked by the MMP inhibitor batimastat. Furthermore, in isolated chondrocytes, C(2) stimulated the expression of MMP-1, 3, and 13 at the mRNA level, MMP activity, and MMP-3 production. Ceramide also caused chondrocyte apoptosis at doses ranging from 10(-5) to 10(-4) M. This study supports the hypothesis that ceramide might play a mediatory role in both matrix degradation and apoptosis in processes of cartilage loss such as those observed in osteoarthritis.

[Antero-posterior lesions of the superior glenoid labrum. Magnetic resonance evaluation]. / La lesione antero-posteriore del labbro glenoideo superiore della spalla. Valutazione con Risonanza Magnetica.

PURPOSE: To assess MR potentials in the evaluation of superior glenoid labrum disease and possible associated conditions of the rotator cuff and of the anterior mechanism of the shoulder. MATERIAL AND METHODS: We retrospectively evaluated 51 patients (age range 18 to 53 years) with a diagnosis of anteroposterior lesion of the superior glenoid labrum. MR examinations were performed with a 0.2 T permanent magnet and a dedicated coil, using T1- and T2-weighted SE sequences on mostly coronal-oblique planes. Slice thickness was 4 mm. In 8 cases, the examination was completed with intra-articular injection of contrast agent. Twenty-eight patients were submitted to surgery (arthrotomy in 7 cases; arthroscopy in 21 cases). RESULTS: We considered only the cases with surgical confirmation and divided them into 2 groups: 15 patients with isolated alteration of the superior glenoid labrum and 13 patients with an anteroposterior lesion of the glenoid labrum associated with disease of the rotator cuff or of the anterior mechanism of the shoulder. MRI demonstrated 5 cases of superior labrum irregularities at the level of its glenoid insertional portion (type I lesion); 6 cases of detachment of the superior portion of the labrum (type II); 9 cases of bucket handle tear of the superior labrum with involvement of the insertional portion of the long head of the biceps tendon (type III); 8 cases of superior labrum tear extending within the long head of the biceps tendon (type IV). In the patients with associated disease MRI demonstrated supraspinatus tendon tear in 5 cases, lesion of the labrum also in its anteroinferior portion in 1 case, Hill-Sachs intraspongious fracture with involvement of the inferior glenohumeral complex in 1 case, and complete tear of the rotator cuff in 7 cases. Subsequent surgery always confirmed the presence of associated lesions, while the superior labrum lesion was not confirmed in 3 patients. In 4 cases, surgical findings provided a different classification of the lesion type than MRI. DISCUSSION: In the presence of a type I anteroposterior lesion of the superior glenoid labrum, coronal MRI can depict the loss of the triangular shape of the labrum. Type II lesions show detachment of the labrum, which appears on the MR images as a high signal intensity band passing through the labrum with caudocranial orientation. A superior glenoid labrum tear with a low signal intensity area within the joint indicates a type III lesion. Complete tear of the superior glenoid labrum with involvement of the long head of the biceps tendon demonstrated on the coronal T1-weighted SE and T2-weighted GE sequences is a sign of a type IV lesion. CONCLUSIONS: MRI can be a valuable diagnostic technique in type III and IV lesions of the superior glenoid labrum. It often provides important information about the possible presence of associated diseases, especially of the rotator cuff, which are helpful for treatment planning.

[Magnetic resonance imaging of hepatic focal lesions: dynamic contrastographic evaluation with gadolinium versus reticulo-endothelial hepato-specific contrast media]. / Risonanza Magnetica delle lesioni focali epatiche: valutazione contrastografica dinamica con gadolinio vs mezzo di contrasto epatospecifico reticolo-endoteliale.

PURPOSE: To compare the potentials of AMI-25 (Endoren) to those of Gadolinium with the dynamic contrast-enhanced technique in the differential diagnosis of focal liver lesions. MATERIAL AND METHODS: Forty patients with at least one focal liver lesion diagnosed at US underwent MRI. We used a 1.5 T unit and employed single-shot half-Fourier T2-weighted FSE and spoiled gradient-echo T1-weighted sequences before and after Gadolinium injection. Multiple acquisitions were obtained during the arterial, portal and delayed phases. Twenty-four to 48 hours later T2*-weighted GRE and SPGR/90 degrees sequences were obtained after AMI-25 administration. In the characterization of solid lesions the gold standard was biopsy performed with a shearing needle; for the diagnosis of angiomas and of 11 metastatic lesions we considered follow-up and clinical data as important diagnostic elements. RESULTS: We found 12 hepatocarcinomas, 14 metastases, 4 cases of focal nodular hyperplasia (FNH), 4 adenomas and 6 angiomas. The diagnosis was correct and confirmed by the conventional examination in all cases but 2 adenomatous lesions and 2 angiomas. Precontrast studies showed slight hyperintensity in 2 of 4 cases of FNH, while the other 2 lesions appeared isointense and were therefore detected only on postcontrast images, where there was contrast agent uptake during the arterial phase and rapid washout. We found only one central scar hyperintense on T2- and hypointense on T1-weighted images. After AMI-25 administration all lesions appeared isointense to surrounding parenchyma on T2* GRE sequences. Adenomas were isointense in the precontrast phase and postcontrast 3 of them showed strong Gadolinium uptake and rapid washout. After AMI-25 two of the 4 lesions were hyperintense while the other two were isointense to the parenchyma. Four of 6 angiomas exhibited a typical pattern characterized by signal hyperintensity on T2-weighted sequences and on AMI-25-enhanced T1- and T2-weighted sequences. Two angiomas were supposed to be of malignant nature but histology showed the presence of a strong fibrotic component. Hepatocarcinomas could be detected on precontrast images. After Gadolinium administration 10 lesions appeared hyperintense in the arterial phase and 2 were hypointense. After AMI-25 all lesions exhibited homogeneous signal hyperintensity and appeared slightly bigger than on Gadolinium-enhanced images. The metastases were only partly demonstrated by MRI. Postgadolinium studies showed 13 lesions with hyperintense signal in the portal phase. AMI-25 administration detected 14 lesions that appeared slightly bigger than on Gadolinium-enhanced images. CONCLUSIONS: AMI-25 can help also in characterizing primary lesions with an atypical signal pattern after contrast agent administration thanks to its intrinsic capability of accumulating in benign lesions. However it remains difficult to characterize well differentiated hepatocarcinomas and adenomas. Finally, AMI-25 improves MR capabilities in detecting secondary lesions and possible satellite nodules.

[Symptomatic renal metastases of bronchial carcinoma]. / Métastases rénales symptomatiques d'un carcinome bronchique.

Renal metastasis from carcinoma of the lung is rarely a clinical problem. Autopsic series however prove that the kidney is a frequent metastatic organ (20%). We report the case of a 43-years-old male patient affected with a squamous cell carcinoma of the lung, with bilateral renal extension. These secondary localizations were detected through a left flank pain prior to a systemic inflammatory response syndrome. The absence of hematuria (even microscopic) contrasted with the importance of the lesions. The age, along with the poor general state of our patient and the absence of any CT specificity justified an exploratory lobotomy. The pathologic analysis of the renal biopsies confirmed the metastatic nature of the lesion.

Health care ethics: models of the provider-patient relationship.

Societal changes and ethical issues in health care have been responsible for the evolution of the models of the provider-patient relationship. As health care providers we must recognize the ethical and moral issues inherent in the provider-patient relationship and its impact on health care and our society today.