Insights from examination of hearts from adults dying suddenly to the understanding of congenital cardiac malformations

Congenital heart disease is a rare but important finding in adults who experience sudden death. Examination of the congenitally malformed heart has historically been considered esoteric and best left to those with expertise. The Cardiac Risk in the Young cardiovascular pathology laboratory based at St George's University of London has now received over 6,000 cases. Of these, 21 congenitally malformed hearts were retained for research and educational purposes. Hearts were assessed using sequential segmental analysis, and causes of death were adjudicated based on thorough macroscopic examination and histology. Congenital malformations that were encountered included atrial septal defects, ventricular septal defects, tetralogy of Fallot, and transposition of the great arteries in both its regular and congenitally corrected variants. Findings also included hearts with mirror-imaged and isomeric atrial appendages. Direct causes of death included myocardial fibrosis, pulmonary hypertension, and hemorrhage. A small but notable proportion did not reveal a substrate for arrhythmia, raising the question of whether the terminal event was due to the congenital heart disease itself, or an underlying channelopathy. Here, we demonstrate the value of simple sequential segmental analysis in describing and categorizing the cases, with the concept of the “morphological method” serving to identify the distinguishing features of the cardiac components. Clin. Anat. 33:394–404, 2020. © 2019 Wiley Periodicals, Inc.     

Economic Issues in the Treatment of BPH

The long-term cost of effective management for benign prostatic hyperplasia (BPH) remains an important issue in pharmacoeconomics because about 25% of men aged 50 yr and older experience voiding problems due to BPH. With the ageing population and the increase in the percentage of patients with BPH for whom any type of treatment can be considered, a substantial increase in total costs to society can be expected. The up-front costs of interventional approaches to BPH are being replaced by a pattern of long-term medical and preventive therapy. The age-adjusted rate of transurethral resection of the prostate (TURP) reached a high point in 1987 and TURP rates, but not costs, have been in decline ever since. Mean 1-yr treatment costs (medical therapy and TURP) have been estimated in a pan-European study to be 858 Euros per patient, 75% of which were medication costs. Using a 2-yr time frame for treatment, Medicare costs for finasteride, terazosin, and TURP have been estimated as $3874, $2161, and $1820, respectively. The available models of the total long-term cost for all therapies for BPH remain compromised by a lack of inclusion of indirect costs, the lack of true long-term data and, critically, the lack of human cost information (patient preference). Only medical therapy provides a preventive as well as symptomatic potential and, if all of the issues were fully incorporated, it is likely that medical therapy would be increasingly recognised as economically preferable.     

Nucleolin protein expression in cutaneous melanocytic lesions

Background:  Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions.
Methods:  We studied 193 cases including benign, dysplastic and malignant melanocytic lesions. Nuclear positivity was evaluated by immunohistochemistry and quantified by automated image analysis.
Results:  Most dysplastic and malignant lesions showed high percentages of cells with abnormal patterns of nuclear positivity (Abn+N) consisting in multiple, irregular, positive dots (ID+) and a coarse, irregularly positive nucleoplasm (CNpl+) or both (ID+CNpl+). The patterns CNpl+ and/or ID+CNpl+ were never observed in benign lesions, in which ID+ were also virtually absent. Abn+N% was significantly lower in dysplastic nevi than in primary melanomas and metastases and in primary melanomas than in metastases (p < 0.05). Furthermore, Abn+N was the second powerful prognostic discriminator, after melanoma thickness, and a significantly lower survival was observed in vertical growth phase melanoma patients showing Abn+N in more than 50% of melanoma cells.
Conclusion:  An altered nuclear nucleolin expression seems to accompany melanoma progression. Further investigation on nucleolin functionality and subcellular trafficking could add information on its altered role in melanoma.     

Factors affecting aseptic loosening of 4750 total hip arthroplasties: multivariate survival analysis

Background  

Total hip arthroplasty is a successful surgery, that fails at a rate of approximately 10% at ten years from surgery. Causes for failure are mainly aseptic loosening of one or both components partially due to wear of articular surfaces and partially to design. The present analysis aimed to identify risk factors and quantify their effects on aseptic failure.     

Long-term Doppler echocardiographic evaluation of the right heart after major lung resections.

OBJECTIVE: The effects of major lung resections on cardiac function in the medium and long term have not been thoroughly evaluated. We have studied right heart function with serial Doppler echocardiography in patients undergoing lobectomy and pneumonectomy during 4 years of follow-up after surgery. METHODS: Thirty-six patients undergoing lobectomy and 15 receiving pneumonectomy were evaluated with one- and two-dimensional Doppler standard transthoracic echocardiography before surgery and 1 week, 3 months, 6 months, 1 year, and 4 years postoperatively. We have studied the right midventricular diastolic diameter (RVDD), the right ventricle free wall thickness, the tricuspid valve insufficiency (TVI) and regurgitation jet (TRJ), and the pulmonary artery systolic pressure (PASP). RESULTS: None of the patients died within the first postoperative year. After lobectomy there were no significant modifications of any variable at any time. RVDD progressively increased after pneumonectomy (26.5+/-2.2mm preoperatively vs 34.3+/-7.6 at 4 years; p<0.001). Four years after surgery all patients undergoing pneumonectomy had moderate TVI while only 55% of patients receiving lobectomy showed it (low grade in 50% and moderate in 5%). In this group of patients PASP increased from 26.1+/-2.6 mmHg preoperatively to 34.3+/-7.6 mmHg at 4 years (p<0.00001). CONCLUSIONS: Right ventricle modifications are clearly evident after pneumonectomy and even if they do not show a clear clinical impact they should not be neglected.     

Small-cell neuroendocrine carcinoma of the ampullary region. A clinicopathologic, immunohistochemical, and ultrastructural study of three cases.

We report the clinicopathologic, immunohistochemical, and ultrastructural features of three small-cell neuroendocrine carcinomas of the ampullary region of the duodenum. All patients were men; their ages were 51, 62, and 66 years. The therapy consisted of pancreatoduodenectomy. All patients died of the disease; median survival was 10 months from the diagnosis. The histological appearance was identical to pulmonary and extrapulmonary small-cell carcinoma. The neuroendocrine differentiation was demonstrated ultrastructurally by the presence of dense-core granules, and by the positive immunoreaction for neuron-specific enolase and Leu-7 in each case. One case expressed a focal positivity for chromogranin A (PHE-5) and argyrophilic granules. The same case showed the presence of neurofilaments on frozen material. Neurofilament proteins could not be demonstrated in any case in paraffin sections. Neoplastic cells exhibited cytoplasmic immunostaining for cytokeratins (CAM 5.2) in all cases. In one case, a large number of neoplastic cells (60-70%) exhibited nuclear Ki-67 positivity. We postulate that the disease's histogenesis was from epithelial stem cell expressing both epithelial and neuroendocrine characteristics. The clinical behavior of small-cell neuroendocrine carcinomas of the ampullary region appears to be extremely aggressive, with early metastases and fatal outcome.     

Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.

Piribedil is a non-ergot D2/D3 agonist with a significant antagonist action on alpha2A and alpha2C adrenergic receptor subtypes. This double-blind placebo-controlled study was undertaken to confirm the efficacy of 150 mg/day piribedil po in improving motor symptoms of idiopathic Parkinson's disease (PD) in nonfluctuating patients insufficiently controlled by a stable daily dose of levodopa (L-dopa). Efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) III score as primary criterion over 4 months. A second comparison was planned at 6 months, after possible adjustment of L-dopa. At 4 months, the rate of response, defined as a 30% decrease from baseline on UPDRS III score, was significantly greater with piribedil compared with placebo (56.4% vs. 37.7%; P = 0.040). At 6 months, the better efficacy of piribedil was maintained (61.8% of responders vs. 39.6% on placebo; P = 0.020). The difference between groups on UPDRS III change from baseline reached statistical significance only at 6 months: -10.0 points in the piribedil group vs. -6.7 points in the placebo group (P = 0.037). Secondary end-points were not significantly different. The most frequently reported adverse events were gastrointestinal symptoms (27 of 61 patients in the piribedil group vs. 13 of 54 patients in the placebo group). In conclusion, a 6-month oral administration of 150 mg/day piribedil in combination with L-dopa is well tolerated, except for minor gastrointestinal symptoms at the beginning of the treatment and significantly improves motor symptoms compared with placebo in PD nonfluctuating patients.     

Temporal coupling between transport and grasp components during prehension movements: effects of visual perturbation.

The temporal coupling between the transport and grasp components of prehension movements was investigated through two experiments. In Experiment 1, six normal subjects were required to reach and grasp each of three spheres located at three different distances (Blocked trials). In Experiment 2, a visual perturbation paradigm was used in which the location of the object to be reached and grasped could change at the beginning of arm movement (Perturbed trials). The same subjects participated in both experiments. Kinematics of wrist trajectory (transport component) and of distance between thumb and index finger (grasp component) were analyzed. The results of Experiment 1 showed that the two components could be temporally coupled during their time course. In Experiment 2, the visual perturbation affected both the components, but different times were required by each component to reorganize the movement towards the new target. These different times caused the decoupling of those events that appeared synchronized in Experiment 1. Finally, evidence was found to suggest that planning of grip formation takes into account not only the perceived characteristics of the object, but also the time planned by the transport component to reach the object.     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Modulation of laminin synthesis in human neuroblastoma cells during retinoic acid induced differentiation.

A comparable pattern of morphological neuronal differentiation was induced in the human neuroblastoma cell line SMS-KCNR by treatment with either retinoic acid (RA) or exogenous laminin (LM). LM expression and synthesis by SMS-KCNR was increased upon RA treatment which involved the cell bound, rather than the secreted protein. These data suggest an involvement of LM in the neuroblastoma differentiation process manifested both as an ability of LM to induce a morphological neuronal differentiation and as a selective control on LM metabolism during RA induced neuronal differentiation.