Non-dioxin-like organic toxicant PCB153 modulates sphingolipid metabolism in liver progenitor cells: its role in Cx43-formed gap junction impairment.

The non-dioxin-like environmental toxicant 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153), member of a group of persistent organic pollutants wide-spread throughout the environment, reduces gap junction intercellular communication (GJIC), an event possibly associated with tumor promotion. Since very few studies have investigated the signaling effectors and mode(s) of action of PCB153, and it is known that the gap junction (GJ) protein Cx43 can be regulated by the bioactive sphingolipid (SL) sphingosine 1-phosphate (S1P), this in vitro study mainly addresses whether SL metabolism is affected by PCB153 in rat liver epithelial WB-F344 cells. PCB153 treatment obtained significant changes in the S1P/ceramide (Cer) ratio, known to be crucial in determining cell fate. In particular, an increase in S1P at 30 min and a decrease of the bioactive lipid at 3 h were observed, whereas Cer level increased at 1 h and 24 h. Notably, a time-dependent modulation of sphingosine kinase (SphK), the enzyme responsible for S1P synthesis, and of its regulators, ERK1/2 and protein phosphatase PP2A, supports the involvement of these signaling effectors in PCB153 toxicity. Electrophysiological analyses, furthermore, indicated that the lipophilic environmental toxicant significantly reduced GJ biophysical properties, affecting both voltage-dependent (such as those formed by Cx43 and/or Cx32) and voltage-independent channels, thereby demonstrating that PCB153 may act differently on GJs formed by distinct Cx isoforms. SphK down-regulation alone induced GJIC impairment, and, when combined with PCB153, the acute effect on GJ suppression was additive. Moreover, after enzyme-specific gene silencing, the SphK1 isoform appears to be responsible for down-regulating Cx43 expression, while being the target of PCB153 at short-term exposure. In conclusion, we provide the first evidence of novel effectors in PCB153 toxic action in rat liver stem-like cells, leading us to consider SLs as potential markers for preventing GJIC deregulation and, thus, the tumorigenic action elicited by this environmental toxicant.

Contribution of Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Women with Early Stage Endometrial Cancer: Results of the SENTI-ENDO Study.

BACKGROUND: This study was designed to evaluate detection rate and anatomical location of sentinel lymph node (SLN) at lymphoscintigraphy, to compare short and long lymphoscintigraphy protocols, and to correlate lymphoscintigraphic and surgical mapping of SLN in patients with early-stage endometrial cancer (EC). METHODS: Subanalysis of the prospective multicenter study Senti-endo performed from July 2007 to August 2009. Patients with stage I and II EC received four cervical injections of 0-2 mL of unfiltered technetium sulphur colloid the day before (long protocol) or the morning (short protocol) before surgery. SLN detection used a combined technetium/patent blue labeling technique, and all patients had a systematic bilateral pelvic lymphadenectomy. RESULTS: A total of 133 patients were enrolled in the study and 118 (94.5 %) underwent a lymphoscintigraphy. Of these 118 patients, 44 (37 %) underwent a short protocol and 66 (56 %) a long protocol (data on lymphoscintigraphy were not available in eight patients). Lymphoscintigraphic detection rate was 74.6 % (34 % for short protocol and 60.2 % for long protocol). No difference in the detection rate was observed according to lymphoscintigraphy protocol (p = 0.22), but a higher number of SLN was noted for the long protocol (p = 0.02). Aberrant drainage was noted on lymphoscintigraphy in 30.5 % of the patients. Paraaortic SLNs were exclusively detected using the long protocol. A poor correlation was noted between short (κ test = 0.24) or long lymphoscintigraphy (κ test = 0.3) protocol and SLN surgical mapping. CONCLUSIONS: Our study demonstrates that preoperative lymphoscintigraphy allowed a high SLN detection rate and that long lymphoscintigraphy protocol was associated with a higher detection of aberrant drainage especially in the paraaortic area.

The etiology of low-grade gliomas: pathological and clinical considerations about radiation-induced low-grade gliomas.

The only environmental factor undoubtedly linked to an increased risk of brain tumors (including gliomas) is therapeutic X-rays. We aim to conduct a detailed study of radiation-induced low-grade gliomas, in order to better understand the pathogenesis of such gliomas. Furthermore, we want do prove whether or not there are significant differences, according to clinical features and biological behavior, between this type of tumor and general low-grade gliomas. We analyzed the existent literature of low-grade radiation-induced glioma case reports and other epidemiological reports based on the experience of the senior author. We were able to collect 20 cases of such gliomas. Demographic data and previous X-ray details, along with latency intervals of all patients are provided. The amount of radiation able to cause mutations is not necessarily very high, as tumors occur even after low doses of radiation (as 3-5 GY). The incidence of this kind of tumors may be underestimated and may rise in the future. Care must be taken when observing patients who were irradiated more than 10 years before, especially in the recent years in which access to radiosurgical and radiation therapies has increased in the general population for treating many cerebral pathologies. Radiation-induced low-grade gliomas appear to be different from general gliomas only in terms of age in which they occur. In terms of clinical and biological behavior, there seem to be no differences, even though exceptional cases are reported.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

Safety and feasibility of the adjunct of local chemotherapy with biodegradable carmustine (BCNU) wafers to the standard multimodal approach to high grade gliomas at first diagnosis.

AIM: Among physicians there is still a reluctant attitude in the employment of combined treatment with surgery and intraoperative placement of carmustina 7.7 mg wafers (Gliadel®), followed by standard adjuvant treatment with radiotherapy and concomitant and subsequent chemiotherapy with temozolomide (TMZ), for supratentorial high grade gliomas at first diagnosis. To determine the safety and feasibility of this multimodality sequential adjuvant therapy, we reviewed our single-institution experience, in the light to provide more insights on this continuous multi-stage chemotherapy approach to such a challenging disease as glioblastoma multiforme. METHODS: From February 2006 to January 2008, 32 patients were treated at our institution for cerebral supratentorial high grade glioma with surgery and intraoperative placement of carmustine wafers. No postsurgical complications could be observed. After a median time of 4,8 weeks all patients began adjuvant concomitant radiotherapy with a mean of 60 Gy and TMZ chemotherapy 75 mg/m2 during which weekly hematologic assessments were performed. After 3 to 6 weeks patients commenced adjuvant TMZ, administered 5 days every 28, 200 mg/m2 for not less than 12 cycles. A contrast-enhanced magnetic resonance imaging (MRI) was routinely performed. Median follow-up after surgery was of 6.5 months, ranging from 4 to 23 months. RESULTS: The mean presurgical KPS was of 80 (range: from 60 to 100), and it remained unmodified after adjuvant therapies even at suspension of steroids. In 4 cases there was a radiologic evidence of progression of the disease and the necessity of steroids, with a progression-free survival (PFS) of 6, 8, 9,5 and 13,6 months. One case died 14 months after first operation. All other patients are still alive. CONCLUSION: The integration of local chemiotherapy with carmustine wafers and the standard adjuvant regimen with radiotherapy and concomitant chemiotherapy appears to be safe and feasible, without any adjunctive complication. Promising results on the efficacy require more follow up to be quantified.

Sarcoma metastatic to the brain: a series of 35 cases and considerations from 27 years of experience.

The authors report their 27-year experience regarding 35 cases of supratentorial brain metastasis from sarcoma treated in a single institution: these included ten osteosarcomas, seven leiomyosarcomas, five Ewing sarcomas, four malignant fibrous histiocytomas, three alveolar soft-part sarcomas (ASPS), two rhabdomyosarcomas, one liposarcoma, and three unclassified sarcomas. The first 15 cases of the series have already been described in a previous publication. Median survival after craniotomy was 9.8 months (range: 4-24). In patients with preoperative Karnofsky performance score (KPS) > 60 it was 12.8 months (range: 6.5-24 months) versus 5.4 months for those patients with a KPS < or = 60 (P = 0.01). Eight patients had more than one lesion, six of which were treated in the last ten years. Of the three patients with ASPS, the first two were alive at 15 and 20 months (before being lost to follow-up) whereas the third patient is alive at 24 month follow-up. The authors conclude that surgery is more effective in treating selected patients with sarcoma metastatic to the brain, and that patients with metastasis from ASPS have good prognosis when submitted to surgical treatment. The complete removal of all brain metastases "en bloc" and a KPS > 60 are associated with the best prognosis. Finally, it seems that surgical indications for multiple brain metastases from sarcoma have increased during the last ten years.

[Evolution of surgical operations for female for stress urinary incontinence in gynaecology departments of Parisian public hospitals between 2002 and 2006]. / Evolution des interventions chirurgicales pour incontinence urinaire d'effort dans les services de chirurgie gynécologique de l'Assistance publique des Hôpitaux de Paris entre 2002 et 2006.

OBJECTIVE: To appreciate the evolution of the current surgical practice for female for stress urinary incontinence (SUI) in the gynaecologic surgery departments of Parisian public hospitals in three different periods of 12 months (2002-2003, 2003-2004, and 2006). PATIENTS AND METHODS: The 16 departments were surveyed by postal questionnaire about their surgical practice for the treatment of female SUI. The number, the type of operation, the type of suburethral tapes and their surgical routes were detailed. RESULTS: The participation rate in the survey was 87.5% (14/16) for the first two studied periods and 75% (12/16) for the last one. The number of SUI procedure decreases between the three periods (586, 505, and 263 procedures, respectively; p<0.001). Suburethral slings represent the technique of choice for SUI (86.2% in 2002-2003; 92.7% in 2003-2004, and 98.1% in 2006). Other practices are exceptional. The transobturator approach has widely progressed and became the preferred one in 2006 (31.1%; 64.5%; 95.4% in 2006; p<0.001). No transobturator route was privileged. TVT procedures have decreased between the three studied periods (48.3%, 36.5%, and 4.6% in 2006; p<0.001). TVT-O is the preferred sling in 2006 (120/258, 46.5% of suburethral tapes). DISCUSSION AND CONCLUSION: Suburethral tape placement is nowadays the main surgical treatment for female SUI amongst members in gynaecology departments in Parisian public hospitals. The transobturator approach is preferred.

Prenatal evaluation of a scrotal mass using a high-frequency probe in the diagnosis of inguinoscrotal hernia.

Whereas inguinal hernia is a common pediatric disease, fetal inguinal hernia is rarely diagnosed because intra-abdominal pressure usually occurs only after birth. We report a case of prenatal diagnosis of a scrotal mass at 35 weeks' gestation. The initial differential diagnosis included hydrocele, testicular teratoma and testicular torsion, but inguinoscrotal hernia was considered the most likely diagnosis when further ultrasound imaging using a high-frequency probe demonstrated bowel loop movements around the mesenteric artery. This diagnosis was confirmed postnatally.

Effect of pinching-evoked pain on jaw-stretch reflexes and exteroceptive suppression periods in healthy subjects.

OBJECTIVE: To investigate the influence of conditioning cutaneous nociceptive inputs by a new "pinch" model on the jaw-stretch reflex and the exteroceptive suppression periods (ES1 and ES2) in jaw muscles. METHODS: The jaw-stretch reflex was evoked with the use of a custom-made muscle stretcher and electrical stimuli were used to evoke an early and late exteroceptive suppression period (ES1 and ES2) in the jaw-closing muscles. Electromyographic (EMG) activity was recorded bilaterally from the masseter and temporalis muscles. These brainstem reflexes were recorded in 19 healthy men (28.8+/-1.1 years) during three different conditions: one painful clip applied to the earlobe; one painful clip applied to the nostril, and four painful clips applied simultaneously to the earlobe, nostril, eyebrow, and lower lip. Pain intensity induced by the application of the clips was scored continuously by the subjects on a 100mm visual analogue scale (VAS). RESULTS: The highest VAS pain scores were evoked by placement of four clips (79+/-0.5mm). There was no significant modulation of the jaw-stretch reflex (ANOVAs: P=0.929), the ES1 (P=0.298) or ES2 (P=0.082) in any of the three painful conditions. CONCLUSIONS: Intense and tonic cutaneous pain could be elicited by this new "pinch" pain model; however, there was no significant modulation on either excitatory or inhibitory brainstem reflex responses. SIGNIFICANCE: The novel observation that high-intensity pinch stimuli applied to the craniofacial region fail to modulate two different brainstem reflexes is in contrast to other experimental pain studies documented facilitation of the jaw-stretch reflexes or inhibition of exteroceptive suppression periods. The clinical implication of the present findings is that only some craniofacial pain conditions could be expected to show perturbation of the brainstem reflex responses.

Hemangioblastoma of the filum terminale. Case report and review of the literature.

Hemangioblastomas of the filum terminale are particularly rare tumors. The authors present the case of a 62-year-old woman with a 6 month history of low-back-pain, who underwent surgery for the removal of an hemangioblastoma affecting the cauda at L2-L3 level. This highly vascularized tumour is tightly adherent to the filum terminale and hence is a very challenging pathology to remove. Histologically it consisted in vascular structures interposed to a network of capillary-like vessels, surrounded by stromal cells. MRI, angiography with pre-surgical embolization, and radical surgery represent the focal points in the diagnosis and treatment of these tumours. The most relevant literature has been carefully reviewed.

Betalains increase vitexin-2-O-xyloside cytotoxicity in CaCo-2 cancer cells.

Vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L. (BVc) seeds, betaxanthin (R1) and betacyanin (R2) fractions from Beta vulgaris var. rubra L. (BVr) roots were combined and tested for cytotoxicity in CaCo-2 colon cancer cells. XVX was the most cytotoxic molecule, but the combination of XVX with R1 and R2 significantly prolonged its cytotoxicity. Cytotoxicity was mediated by the intrinsic apoptotic pathway, as shown by an increase in Bcl2-like protein 4, cleaved Poly ADP-Ribosyl Polymerase 1 and cleaved Caspase 3 levels with a parallel decrease in anti-apoptotic protein B-cell leukemia/lymphoma 2 levels. R1 and R2, used alone or in combination, reduced oxidative stress triggered by H2O2 in CaCo-2 cells. Betalains dampened cyclooxygenase-2 and interleukin-8 mRNA expression after lipopolysaccharide induction in CaCo-2, showing an anti-inflammatory action. Our results support the use of a cocktail of R1, R2 and XVX as a chemopreventive tool against colon cancer.

Betacyanins enhance vitexin-2-O-xyloside mediated inhibition of proliferation of T24 bladder cancer cells.

Betacyanins (BC) were purified from beetroot (Beta vulgaris var. rubra L.) and tested, alone or in combination with vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L., for their ability to reduce the proliferation rate in T24 bladder cancer cells. Combination of BC and XVX exhibited a synergistic effect concerning the inhibition of proliferation in T24 cancer cells at 24 and 48 h but not after 72 h of incubation. The induction of apoptosis was evidenced by means of fluorescence activated cell sorting (FACS) analysis, as well as through the increase in caspase 3 and 8 activities. Using RTqPCR experiments, it was shown that the combination of XVX + BC was able to enhance the expression levels of pro-apoptotic BAX and downregulate anti-apoptotic BIRC5 (survivin), as well as pro-survival CTNNB1 (ß-catenin). The most evident effect of BC was the increase of the activity of caspase 8, leading to induction of extrinsic apoptosis. Moreover, XVX, BC and their combination showed no cytotoxic effect on normal human skin NCTC 2544 keratinocytes. These results demonstrated the efficacy and the mechanisms of the action of BC and XVX, extracted from edible plants, and suggested that a diet or a nutrition supplement, enriched with these bioactive molecules, could be used in the prevention of human bladder cancer.

Central nervous system mesenchymal chondrosarcoma.

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature.

Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.

Acute effect of cigarette smoking on glucose tolerance and other cardiovascular risk factors.

OBJECTIVE: To investigate the acute effect of cigarette smoking on glucose tolerance, insulin sensitivity, serum lipids, blood pressure, and heart rate. RESEARCH DESIGN AND METHODS: This nonrandomized experimental control trial in a tertiary care center included 20 healthy chronic smokers and 20 age-, sex-, and BMI-matched healthy volunteers. Two oral glucose tolerance tests (OGTTs) were performed on each subject. Three cigarettes were smoked during the first 30 min in one of the tests. Serum glucose, insulin, and C-peptide levels were measured every 30 min; the area under the curve (AUC) and the insulin sensitivity index (ISI) were calculated; serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were measured at 0 and 180 min; and blood pressure and heart rate were recorded every 5 min throughout 180 min. RESULTS: Smoking acutely impaired glucose tolerance: the AUC for glucose in smokers was 25.5 +/- 1.03 mmol/l (mean +/- SE) (95% CI 22.9-28) during the smoking OGTT and 21.8 +/- 0.85 mmol/l (CI 19.2-24.3) in the control OGTT (P < 0.01); in nonsmokers, it was 19.7 +/- 0.3 mmol/l (CI 18.8-20.5) in the smoking OGTT and 18.7 +/- 0.35 mmol/l (CI 17.8-19.5) in the control OGTT (P < 0.05). Smoking acutely increased serum insulin and C-peptide levels and decreased ISI only in smokers: ISI in smokers was 55 +/- 2.8 (CI 47.4-62.6) in the control OGTT and 43 +/- 2.7 (CI 35.4-50.6) in the smoking OGTT (P < 0.05). Smoking acutely caused a rise of serum total cholesterol levels in both groups and increased LDL cholesterol and triglyceride serum levels significantly only in smokers (P < 0.05). A significant rise of blood pressure and heart rate while smoking was present in all the subjects. CONCLUSIONS: Smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol and triglyceride levels, and raised blood pressure and heart rate. These findings support the pathogenetic role of cigarette smoking on cardiovascular risk factors.

[Moderate preterm birth 34-37 weeks: Description of immediate neonatal causes and consequences in a level 2 maternity]. / Prématurité modérée 34-37SA : description des causes et conséquences néonatales immédiates dans une maternité de niveau 2.

OBJECTIVES: In France, 75% of annual preterm births happen between 34 and 36 weeks+6 days. This study's goal is to describe the main causes and short-term consequences. METHODS: Two hundred and ninety-seven computerized files of patients who gave birth between 34 and 36 weeks+6 days at the hospital Foch's maternity were analyzed retrospectively. Descriptive statistical analysis was done with XLSTAT 2008. RESULTS: Among the 6028 births, 4.9% happened between 34 and 36 weeks+6 days and 43.1% of these births were medically induced. The two main causes of induced late preterm birth were: pre-eclampsia (28.9%) and premature rupture of membranes (25%). In spontaneous deliveries, newborns less often require respiratory support at birth (17.2% vs 31%; P=0.02) and are significantly less likely to be hospitalized in neonatology (54% vs 72.3%; P<0.01). C-section rates (71.1% vs 17.75%; P<0.01) and post-partum hemorrhages' probability (10.2% vs 3%; P<0.01) are significantly higher than for medically induced deliveries. CONCLUSION: Better knowledge of late prematurity causes and consequences would help limit medically induced births after 34 weeks.

Face immersion reflex for diagnosis of diabetic cardiovascular autonomic neuropathy.

To evaluate face immersion reflex (FIR) as a diagnostic test for diabetic autonomic neuropathy, we studied 15 patients with diabetic cardiovascular autonomic neuropathy--defined as the presence of at least two other abnormal autonomic tests-and 15 healthy subjects as a control group. All patients underwent six different autonomic tests including deep breathing R-R variation, Valsalva maneuver, heart rate and blood pressure response to standing, intravenous atropine injection and FIR. FIR test was considered positive for autonomic neuropathy if heart rate did not decrease at least 15% of the basal rate after 10 sec of immersion. FIR was positive in all the diabetic patients and negative in the 15 controls. Its sensitivity was higher than any other single autonomic test (p < 0.025). Considering two abnormal autonomic tests as a gold standard for diabetic cardiovascular autonomic neuropathy, sensitivity was 100% for FIR, 66% for deep breathing R-R variation and Valsalva maneuver, 53% for blood pressure (BP) response to standing and 20% for i.v. atropine injection. All the test were highly specific. We conclude FIR test should be considered among diagnostic tests for diabetic cardiovascular autonomic neuropathy.

Hyperinsulinemia in patients with coronary heart disease in absence of overt risk factors.

The objective of the study was to determine if male subjects with coronary atherosclerotic heart disease (CHD) without major CHD risk factors have hyperinsulinemia and related metabolic changes. Previous studies suggested that hyperinsulinemia is a CHD risk factor, but they did not entirely exclude concurrent metabolic abnormalities. A prospective, comparative, cross-sectional study in a tertiary care teaching hospital in Mexico City was conducted in 15 men who had suffered myocardial infarction 6 to 24 months before and had significant coronary occlusion on angiography. Control group was formed by 15 age-matched healthy men. None had hypertension, obesity, diabetes, gout, glucose intolerance or hyperlipidemia. Body mass index (BMI), waist/hip ratio (WHR), blood pressure (BP); oral glucose tolerance test (OGTT) with measurement of serum glucose, insulin and C-peptide every 30 min for 2 h, fasting serum cholesterol, triglycerides and uric acid, areas under curve (AUC) of glucose and insulin, insulin/glucose ratio and insulin sensitivity index were calculated. BMI, WHR and BP were similar in both groups. Fasting and post-load serum glucose and insulin concentrations were significantly higher in CHD than in control group (p < 0.01); fasting glucose 5.9 +/- 0.6 vs. 4.8 +/- 0.7 nmol/1, 2-h glucose 8.3 +/- 0.6 vs. 7.3 +/- 0.9 mmol/l, fasting insulin 17.5 +/- 1.2 vs. 15.3 +/- 1.7 pmol/l, 2 h insulin 448 +/- 108 vs. 282 +/- 87 pmol/l in CHD and control group, respectively. AUC of glucose, AUC of insulin, insulin/glucose ratio, post load C-peptide, serum cholesterol, triglycerides and uric acid levels were also significantly higher in CHD than in healthy controls. Insulin sensitivity index was significantly lower in patients with CHD (27.7 +/- 8.3) than in healthy control subjects (73.9 +/- 18) (p < 0.001). Patients with CHD have hyperinsulinemia and subtle metabolic abnormalities related with insulin resistance even in absence of overt risk factors.

Tru-cut needle biopsy of subcutaneous fat in the diagnosis of secondary amyloidosis in rheumatoid arthritis.

In order to investigate the presence of secondary amyloidosis in patients with rheumatoid arthritis (RA), we performed an abdominal subcutaneous fat biopsy with a tru-cut needle in 50 patients. The tissue was stained with Congo red and was observed with polarized light microscopy. We found amyloid deposits in 78% of our patients. We randomly selected ten patients with a positive biopsy and a second procedure was performed. Tissues were studied with electron microscopy. We found unbranched fibrils characteristic of amyloid in all of them. We found a direct correlation with rheumatoid factor titers: the more intense the amyloid deposit, the higher the rheumatoid factor titers (p < 0.001). We did not find any correlation between amyloid deposits and clinical manifestations of disease. Amyloid deposits in RA are more frequent than previously thought, and their clinical importance remains to be determined.

Left ventricular diastolic dysfunction secondary to hyperglycemia in patients with type II diabetes.

Diabetes mellitus type II, a cause of preclinical left ventricular dysfunction that can progress to cardiac insufficiency ventricular dysfunction in diabetic patients, is attributed to systemic arterial hypertension, or ischemic cardiopathy. Diastolic ventricular dysfunction takes place during the course of diabetes mellitus. The purpose of the present article is to report on the influence of hyperglycemia on the left ventricular diastolic dysfunction independently of dyslipidemia, obesity, and systemic arterial hypertension, usually present in diabetic patients. Left ventricular diastolic function was studied by Doppler echocardiography in asymptomatic type II diabetic patients without ischemic or valvular cardiopathies, cardiomegaly, or systemic arterial hypertension. Two groups of patients were integrated: patients with and without left ventricular diastolic dysfunction, i.e., groups A and B, respectively. Glycemia, cholesterol, triglycerides, and body mass index (BMI) were determined in each subject. Bivariate statistical tests (Student t, chi-square, or Mann-Whitney U tests) were applied to study the influence of the previously mentioned variables on the ventricular diastolic function. To evaluate the influence of hyperglycemia on ventricular diastolic function separately from dyslipidemia, systemic arterial hypertension, and the influence of obesity, logistic regression, and multivariate statistical analysis were applied. Independently of dyslipidemia and obesity, a relationship was found between hyperglycemia and diastolic dysfunction of the left ventricle in patients belonging to group A (p <0.05, odds ratio [OR] 12.1). No statistical significance was found between glycemia and the diastolic function of the left ventricle in group B patients. Even in type II diabetic patients without cardiopathy, uncontrolled hyperglycemia provokes diastolic left ventricular dysfunction.