Morpho-functional study of peritoneum in peritoneal dialysis patients

BACKGROUND: Structure and function of the peritoneal membrane (PM) are impaired on peritoneal dialysis (PD). The aim of this study was to examine the relationship between dialytic parameters and histological and functional characteristics of the peritoneum of PD patients. METHODS: A peritoneal biopsy (PB) was performed on 31 PD patients during catheter removal due to malfunction or after drop-out from treatment. PB was performed at least 5 cm from the catheter insertion. For each patient PM transport was evaluated by the last peritoneal equilibration test (PET) before PB. Each daily glucose load was calculated. Tissue was formalin-embedded and stained for histological and immunohistochemical studies. RESULTS: (1) Duration of treatment was longer in patients with mesothelial impairment. (2) Patients showing sub-mesothelial sclerosis (SS) and those with impairment of submesothelial basement membrane and subendothelial vascular membrane (SVM) were submitted to a larger daily glucose load. (3) SS exceeding 50 mm was more frequent among high transporters, who were exposed to larger daily glucose load compared to medium-high transporters. (4) Mesothelial loss correlated to SS and vascular alterations. (5) SS was related to vascular injuries but not to inflammatory infiltrate. CONCLUSIONS: SS is not constant in PD patients and is not a prominent factor in treatment drop-out. Mesothelial impairment seems to be mainly related to duration of PD treatment. Glucose load seems to mainly damage the sub-mesothelial layer.     

Nanotechnologies and microchips in genetic diseases

Microarrays or microchips represent a new area of high technology, which will completely change the methodological approach to basic research and clinical diagnostics. This technology can be used for genotyping, expression profiling and proteome analysis. Genetics and molecular medicine have an expanding need for rapid genotyping, mutational analysis and DNA re-sequencing technologies, i.e. microarrays that have a clear potential for miniaturization, parallelization, and automation and enable high-throughput screening. Expression profiling technology is a new tool for investigating expression patterns, identifying new disease genes either for monogenic disorders or for complex traits, identifying new functional and cellular relationships and identifying new pathways and possible related drugs. This technology has been successfully applied to the study of complex traits, i.e. cardiovascular diseases, cancer and type II diabetes, providing new insights into possible pathogenetic mechanisms and new therapeutical approaches. Finally, microarray can further improve proteome analysis. This review discusses these points.     

Does this patient have pulmonary embolism?

Sanjeev D. Chunilal, MB, ChB, FRACP, FRCPA; John W. Eikelboom, MBBS, MSc, FRACP, FRCPA; John Attia, MD, PhD, FRCPC; Massimo Miniati, MD; Akbar A. Panju, MBChB, FRCPC; David L. Simel, MD; Jeffrey S. Ginsberg, MD, FRCPC

JAMA. 2003;290:2849-2858.

Context  Experienced clinicians' gestalt is useful in estimating the pretest probability for pulmonary embolism and is complementary to diagnostic testing, such as lung scanning. However, it is unclear whether recently developed clinical prediction rules, using explicit features of clinical examination, are comparable with clinicians' gestalt. If so, clinical prediction rules would be powerful tools because they could be used by less-experienced health care professionals to simplify the diagnosis of pulmonary embolism. Recent studies have shown that the combination of a low pretest probability (using a clinical prediction rule) and a normal result of a D-dimer test reliably excludes pulmonary embolism without the need for further testing.

Objective  To evaluate and demonstrate the accuracy of pretest probability assessment for pulmonary embolism using clinical gestalt vs clinical prediction rules.

Data Sources  The MEDLINE database was searched for relevant articles published between 1966 and March 2003. Bibliographies of pertinent articles also were scanned for suitable articles.

Study Selection  To be included in the analysis, studies were required to have consecutive, unselected patients enrolled; participating physicians in the studies, blinded to the results of diagnostic testing, had to estimate pretest probability of pulmonary embolism; and validated diagnostic methods had to be used to confirm or exclude pulmonary embolism.

Data Extraction  Three reviewers independently scanned titles and abstracts for inclusion of studies. An initial MEDLINE search identified 1709 studies, of which 16 involving 8306 patients were included in the final analysis.

Data Synthesis  A clinical gestalt strategy was used in 7 studies, and in the low, moderate, and high pretest categories, the rates of pulmonary embolism ranged from 8% to 19%, 26% to 47%, and 46% to 91%, respectively. Clinical prediction rules were used in 10 studies, and 3% to 28%, 16% to 46%, and 38% to 98% in the low, moderate, and high pretest probability groups, respectively, had pulmonary embolism.

Conclusions  The clinical gestalt of experienced clinicians and the clinical prediction rules used by physicians of varying experience have shown similar accuracy in discriminating among patients who have a low, moderate, or high pretest probability of pulmonary embolism. We advocate the use of a clinical prediction rule because it has shown to be accurate and can be used by less-experienced clinicians.

     

Severe chronic sensory-motor polyneuropathy: coexistence of 3 unrelated etiologies in a type 1 diabetic patient. A case report and review of the literature

We present the case of a 58-year-old man, who has suffered from type 1 diabetes mellitus since he was young. He had monoclonal IgM kappa gammopathy of undetermined significance and high anti-MAG antibody titer. He developed a polyneuropathic picture with the clinical and laboratory features of chronic inflammatory demyelinating polyneuropathy within the span of approximately 2 years. He benefited from IV administration of high doses of immunoglobulins. Investigation of all parameters, but particularly of the clinical phenotype, can lead to a better definition of the polyneuropathic picture, especially for therapeutic and prognostic purposes.     

Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O2- production

Experimental studies have suggested that TNF alpha, a pro-inflammatory cytokine, may contribute to the deterioration of cardiovascular function through various mechanisms, including the generation of reactive oxygen species. It has not yet been demonstrated whether TNF alpha has prooxidant activity in patients with heart failure, and what the mechanism eventually resulting in this effect are. We analyzed 42 patients (38 men and 4 women, aged 26 to 74 years) with heart failure, secondary to idiopathic dilated cardiomyopathy (n=21), coronary artery disease (n=15), and valve disease (n=6), and 20 controls (18 men and 2 women, aged 49 to 67 years). Ten patients were in class I, 9 in class II, 15 in class III and 8 in class IV according to NYHA Classification. Blood samples were obtained from each patient to evaluate basal and collagen-induced platelet O(2)(-) production, and plasma TNF alpha. In vivo results showed increased platelet O(2)(-) production and plasma TNF alpha levels in NYHA class III-IV compared with that in controls or in NYHA I-II (p<0,001); platelet O(2)(-) production correlated significantly (R=0,6; p<0,01) with TNF alpha plasma levels. In vitro studies showed TNF alpha dose-dependently (5-40 pg/ml) induced platelet O(2)(-) production, and that this effect was significantly inhibited by its specific inhibitor, WP9QY (1 microM); aspirin (100 microM), AACOCF(3), a specific PLA(2) inhibitor (14 microM), and DPI, an inhibitor of NADPH oxidase, significantly inhibited TNF alpha-mediated platelet O(2)(-) production. This study suggests that in patients with heart failure, enhanced platelet O(2)(-) production is mediated by TNF alpha via activation of arachidonic acid and NADPH oxidase pathways.     

Peripheral artery disease in type 2 diabetes: the role of fibrinolysis

The aim of the present study is to verify the relationship between peripheral artery disease (PAD) and some coagulation/fibrinolysis parameters in type 2 diabetic patients. Sixty-three type 2 diabetic patients, without PAD, were studied at baseline and after 4 years. Assessments included tissue-Plasminogen Activator (t-PA), Plasminogen Activator Inhibitor-1 antigen (PAI-1 Ag), Plasminogen Activator Inhibitor-1 activity (PAI-1 Act), Plasminogen (Pl), Fibrin peptide A (FPA), Fibrinogen (Fr), and the ankle/brachial pressure index (ABI). We observed a significant difference between diabetic patients and controls as regards tPA (11.8 +/- 5.4 vs. 6.6 +/- 3.0 ng/ml; p <0.05) and PAI-1 Act (17.8 +/- 9.2 vs. 11.7 +/- 6.6 ng/dl; p <0.005). After 4 years 13 diabetic patients became vasculopathic and, at baseline, had significantly lower tPA (8.9 +/- 4.8 vs. 12.5 +/- 5.3; p <0.011), and higher PAI-1 Ag (50.8 +/- 22.2 vs. 32 +/- 22.2; p <0.006), and PAI-1 Act values (24.1 +/- 9.5 vs. 16.1 +/- 8.4; p <0.014), compared with 50 diabetic patients who did not develop PAD after 4 years. These data show that the physiological equilibrium which exists between t-PA and PAI-1 moves towards higher levels in our diabetic patients compared with controls, at baseline, whereas diabetic patients who developed PAD showed a shift towards an antifibrinolytic pathway with diminished t-PA, increased PAI-1 Ag and PAI-1 Act and consequently procoagulant activity. Our study suggests that hypofibrinolysis may be involved in the future onset of PAD in type 2 diabetic patients.     

Extracorporeal life support during and after bilateral sequential lung transplantation in patients with pulmonary artery hypertension

The use of extracorporeal membrane oxygenator instead of standard cardiopulmonary bypass during lung transplantation is debatable. Moreover, recently, the concept of prolonged postoperative extracorporeal membrane oxygenator (ECMO) support has been introduced in many transplant centers to prevent primary graft dysfunction (PGD) and improve early and long-term results. The objective of this study was to review the results of our extracorporeal life support strategy during and after bilateral sequential lung transplantation (BSLT) for pulmonary artery hypertension. We review retrospectively our experience in BSLT for pulmonary artery hypertension between January 2010 and August 2018. A total of 38 patients were identified. Nine patients were transplanted using cardiopulmonary bypass (CPB), in eight cases CPB was followed by a prolonged ECMO (pECMO) support, 14 patients were transplanted on central ECMO support, and seven patients were transplanted with central ECMO support followed by a pECMO assistance. The effects of different support strategies were evaluated, in particular in-hospital morbidity, mortality, incidence of PGD, and long-term follow-up. The use of CPB was associated with poor postoperative results and worse long-term survival compared with ECMO-supported patients. Predictive preoperative factors for the need of intraoperative CPB instead of ECMO were identified. The pECMO strategy had a favorable effect to mitigate postoperative morbidity and mortality, not only in intraoperative ECMO-supported patients, but even in CPB-supported cases. In our experience, ECMO may be considered as the first choice circulatory support for lung transplantation. Sometimes, in very complex cases, CBP is still necessary. The pECMO strategy is very effective to reduce incidence of PGD even in CPB-supported patients.     

Substance abuse and psychopathology

This report evaluates, using DSM III, the psychopathological profile of 226 heroin users taken in at the clinical centre of "Cascina Verde" Therapeutic Community (Milan, Italy) and admitted to a psychotherapeutic, retraining, integrated, both out-and-in-patient treatment. The outcome shows that 30% of subjects are to be diagnosed according to Axis I while 61% are to be considered among Axis II personality disorders. A portion of 16% is to be referred to the "schizophrenic spectrum", 25% has histrionic, narcissistic, antisocial and borderline personality disorders and the remaining are to be referred to an extremely heterogeneous category. The report shows also data concerning Axes IV and V, always according DSM III.