Killer immunoglobulin-like receptors (KIR) and their HLA-ligands in Italian paroxysmal nocturnal haemoglobinuria (PNH) patients.

Paroxysmal nocturnal haemoglobinuria (PNH) is a haematopoietic disorder characterized by expansion of phosphatidylinositol glycan-A-defective progenitor(s). Immune-dependent mechanisms, likely involving a deranged T cell-dependent autoimmune response, have been consistently associated with the selection/dominance of PNH precursors. Natural killer (NK) lymphocytes might participate in PNH pathogenesis, but their role is still controversial. NK activity is dependent on the balance between activating and inhibiting signals. Key component in such regulatory network is represented by killer immunoglobulin-like receptors (KIR). KIR are also involved in the regulation of adaptive cytotoxic T cell response and associated with autoimmunity. This study investigated on the frequency of KIR genes and their known human leukocyte antigen (HLA) ligands in 53 PNH Italian patients. We observed increased frequency of genotypes characterized by ≤2 activating KIR as well as by the presence of an inhibitory/activating gene ratio ≥3.5. In addition, an increased matching between KIR-3DL1 and its ligand HLA-Bw4 was found. These genotypes might be associated with lower NK-dependent recognition of stress-related self molecules; this is conceivable with the hypothesis that an increased availability of specific T cell targets, not cleared by NK cells, could be involved in PNH pathogenesis. These data may provide new insights into autoimmune PNH pathogenesis.

Congenital cataract extraction with primary aphakia and secondary intraocular lens implantation in the posterior chamber.

PURPOSE: To evaluate visual outcomes, eye movement abnormalities, and postoperative complications after secondary posterior chamber intraocular lens (IOL) implantation in aphakic children who had initial LAC correction. METHODS: A retrospective study was carried out on 53 patients (94 eyes). Following aphakic surgery and LAC correction the patients received secondary IOL implantation in the posterior chamber. Special attention was paid to factors that may have influenced their visual outcomes, such as eye movement abnormalities, cataract unilaterality, and cataract density. RESULTS: No association was found between age at surgery and the onset of strabismus (p=0.611) or with visual acuity (p=0.086). However, unilaterality and total cataract density were found to have a negative association with poor vision (p<0.001). Strabismus and nystagmus were found to have a statistically significant negative association with visual acuity (p=0.002). Posterior capsule opacification occurred in six eyes of five patients following cataract extraction; IOL dislocation occurred in four eyes after IOL intraocular implantation, and secondary glaucoma occurred in one eye. CONCLUSIONS: IOL implantation before 12 months of age may be useful in unilateral cataract; in bilateral cataract, simultaneous surgical aphakia, LAC correction, and then IOL implantation at 2.5-3 years of age, together with anti-amblyopic therapy when strabismus or asymmetric cataract density occur, are efficient methods to obtain visual recovery. Extraocular muscle surgery may be required to correct strabismus.

Strabismus in developmental cataract.

PURPOSE: To evaluate the presence of strabismus in patients with developmental cataract rendered pseudophakic and how this influences their visual acuity. METHODS: A retrospective study was carried out on 113 patients with developmental cataract who came under the authors' observation at the outpatient department of the Pediatric Ophthalmology Unit of the University of Federico II of Naples from 1990 to 2005. All patients were followed up for a long period (mean 62 months, range 36-144 months). Age at diagnosis, sex, laterality, age at cataract extraction, morphology, and cataract density were all considered as possible factors associated with strabismus. Visual acuity and ocular motility before and after cataract extraction surgery were especially noted. Statistical evaluation was performed using t-test, Chi-square test, and Fisher exact test. RESULTS: Out of the 113 patients a total of 181 eyes were affected: 68 patients (60%) presented bilateral cataract, 45 patients (40%) monolateral cataract. Strabismus was present in 39 patients (34%) before cataract surgery. Age at cataract diagnosis, age at surgery, sex, and cataract morphology were not found to be statistically associated with strabismus. However, laterality was found to be statistically associated with the onset of strabismus. Cataract density was found to be statistically associated with poor vision. Patients with strabismus presented a non statistically significant lower visual acuity. CONCLUSIONS: Strabismus has a greater incidence in developmental cataract compared to the general population, and can influence visual acuity, especially in monolateral and total cataracts. Intraocular lens implants produced satisfactory visual rehabilitation.

Emotional and cognitive information processing in web-based medical education.

The patient-physician relationship can be conceived as a process of structuring an ill-structured emotional-cognitive problem. So, new methods should be developed in order to capture the relations among emotions and cognitions, and physicians should be educated to recognize the influence of emotions on medical decision-making. The paper describes GRASP, an e-learning application based upon the assumption that cognitions and emotions are dual concepts. The results of a blended e-learning experiment are shown. The students were confronted with a role-playing based illness narrative. Their observations were segmented into information units, and uploaded on the e-learning system DVLN. The set of information units was then transformed into a bipartite graph, and analysed by means of STRUCTURE, an application aimed at grasping the structure of the relations among a set of "objects". The results were compared with Correspondence Analysis. The implications for medical education, medical reasoning, and medical record design are discussed.

Cyclic red blood cell destruction in thalassemia.

A retrospective analysis of time series of hemoglobin (Hb) destruction of 24 children (11 males and 13 females) with thalassemia from the age of 6 to 12 years showed that the Hb destruction rate typically oscillated with an average period of 50 days. A possible relation between the periodism and the severity of the disease is also suggested.

Survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas.

Recent reports have demonstrated an improvement in 5-year actuarial survival of patients with resected ductal adenocarcinoma. The purpose of this study was to determine the factors favoring long-term survival after pancreaticoduodenectomy. Between 1974 and 1995, 75 patients with pancreatic head carcinoma underwent pancreaticoduodenectomy in our department. The overall postoperative mortality rate was 5.3% and morbidity was 24%. Median survival following resection was 17 months. The estimated 1-, 2- and 5-year survival rates were 68%, 46.7% and 18.7%, respectively. Five-year survival was significantly greater for node-negative versus node-positive patients (41.7% vs 7.8%, P < 0.001), for smaller (< 3 cm) versus larger tumours (33.3% vs 8.8%, P < 0.006), and for negative versus positive resection margins (23.3% vs 0, P < 0.001). Other factors, including gender, age, and blood transfusion had no significant effect on survival. The multivariate analysis was done using the Cox proportional hazards model to determine independent prognostic determinants of survival. The presence of positive resection margins was the strongest independent predictor of decreased survival. Lymph node metastasis, tumour size > 3 cm, and poor histologic differentiation were also independent predictors of poor survival. The most favorable subset consisted in 17 patients who had negative resection margins, negative lymph nodes, and tumor size < 3 cm. Their 5-year survival rate was 52.9%.

Factors influencing survival after resection for ductal adenocarcinoma of the head of the pancreas.

BACKGROUND AND OBJECTIVES: Recent reports have demonstrated improvement in the 5-year actuarial survival for patients with resected ductal adenocarcinoma. The purpose of this study is to determine the factors favoring long-term survival after pancreaticoduodenectomy. METHODS: Between 1974 and 1995, 75 patients with pancreatic head carcinoma underwent pancreaticoduodenectomy in our department. RESULTS: Overall postoperative mortality rate was 5. 3% and morbidity was 24%. Median survival following resection was 17 months. Estimated 1-, 2-, and 5-year survival rates were 68%, 46.7%, and 18.7%, respectively. Five-year survival was greater for node-negative than for node-positive patients (41.7% vs. 7.8%, P < 0. 001) and for smaller (<3 cm) than for larger tumors (33.3% vs. 8.8%, P < 0.006). The 5-year survival in patients with negative margins (n = 60) was 23.3%, whereas no patient with positive margins (n = 15) survived at 13 months (P < 0.001). Multivariate analysis, performed by the Cox proportional hazards model, indicated that margin status, lymph node metastasis, tumor size, and poor histological differentiation were independent predictors of poor survival. CONCLUSIONS: Five-year survival for patients undergoing pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas was 18.7%. Survival was greater in the group of patients with negative lymph nodes, tumor size <3 cm, and negative margin status.

P53 immunohistochemistry can identify bronchial dysplastic lesions proceeding to lung cancer: a prospective study.

Dysplasia is an important step in bronchial carcinogenesis and smokers present more dysplastic lesions than nonsmokers. These lesions not always lead to malignancy, so there is a need for additional, preferentially objective, diagnostic markers. To verify whether immunohistochemical overexpression of p53 protein in dysplastic areas could be a predictive marker of the development of lung cancer, we investigated p53 overexpression in 22 bronchial dysplastic lesions obtained by fibrebronchoscopy from heavy smokers who were not diagnosed as having lung cancer and were followed for a 4-yr period. Nine (41%) lesions showed p53-positivity. Seven lung cancers (78%), mostly squamous cell carcinomas, were detected within the follow-up in these patients and 3 in 13 (23%) patients with p53-negative lesions. Lung cancer occurred in all seven patients with dysplastic lesions showing >10% p53 positive nuclei. The positive predictive value of p53 immunostaining for lung cancer was 78%. The negative predictive value of p53 was 77%. p53 staining was not detected in squamous metaplasia lesions without atypia and in normal bronchial epithelium. Our findings provide evidence that p53-overexpression in bronchial dysplastic areas may be a clinically useful marker for identifying patients proceeding to, at least, squamous cell carcinoma and, in addition, may facilitate the detection of occult tumours.

Distance learning, problem based learning and dynamic knowledge networks.

This paper is an attempt to develop a distance learning model grounded upon a strict integration of problem based learning (PBL), dynamic knowledge networks (DKN) and web tools, such as hypermedia documents, synchronous and asynchronous communication facilities, etc. The main objective is to develop a theory of distance learning based upon the idea that learning is a highly dynamic cognitive process aimed at connecting different concepts in a network of mutually supporting concepts. Moreover, this process is supposed to be the result of a social interaction that has to be facilitated by the web. The model was tested by creating a virtual classroom of medical and nursing students and activating a learning session on the concept of knowledge representation in health sciences.

A non-linear model of growth in the first year of life.

Weight gain curves in infancy and childhood show valleys and hills which cannot be simplistically ascribed to random variations, so that they are referred to as pulsatile or pulse growth. Classical mathematical models of human growth, upon which the statistical percentiles are based, do not account for these oscillations. Moreover, statistical curves can hide individual patterns of growth. In the present paper a system dynamics approach to modelling the first year weight gain is suggested which simultaneously accounts for the oscillations of weight gain, for its decreasing trend, and for a more or less marked initial spurt observed approximately in the second month of life. It is suggested that the overall weight growth in the first year is the output of complex hidden non-linear dynamics.

Hepatitis C virus in prisoners.

The purpose of this study was to assess the epidemiology of hepatitis C virus (HCV) in prisoners and outpatients attending our center. 2205 specimens were consecutively obtained under code and screened for anti-HCV by the second generation RIBA test and Hepatitis B core antibody (HBcAb) by CORAB test. After serum samples were tested, we reviewed demographic data and categorized four groups: Intravenous drug abusers (IVDAs), prisoners and apparently healthy subjects and warders. Anti-HCV prevalence was 59.4% in 613 IVDAs, 15.5% in 756 prisoners, 2.6% in 454 healthy subjects and 2.8% in 145 warders. These findings suggest that prisoners may be considered a group at increased risk for HCV infection.

Visual dysfunction in patients with mitochondrial myopathies. II. Contrast sensitivity function.

Contrast sensitivity function with stationary and temporally modulated (8 Hz) black and white vertical sinusoidal gratings was investigated in 11 patients with biopsy-confirmed mitochondrial progressive external ophthalmoplegia. To evaluate contrast sensitivity function results, the contrast sensitivity versus spatial frequency experimental data for each subject were fitted with a second-order polynomial, and the coefficients of the best-fitting function from normal and patient groups were compared. Patients with progressive external ophthalmoplegia, as a group, showed a decreased sensitivity at the intermediate spatial frequencies (i.e., around 1.4 c/deg) with stationary gratings and through a wider range of spatial frequencies with temporally modulated gratings. These findings were confirmed by analyzing contrast sensitivity functions from each individual. The study showed that contrast sensitivity function detects visual function abnormalities noninvasively in a number of patients with mitochondrial progressive external ophthalmoplegia with unaffected Snellen visual acuity.

Renal functional reserve: its significance in normal and salt depletion conditions.

The aim of this study was the evaluation, in healthy subjects, of the renal functional reserve (RFR), that is, the GFR increase induced by a combined infusion of amino acids (AA) and dopamine (D), in conditions of extracellular volume depletion caused by diuretic administration. In particular, this study was undertaken: a) to evaluate whether and to which extent, AA + D can reverse the functional GFR impairment induced by salt depletion, without volume restoration; b) to study whether any relationship may be found between the GFR in normal condition (the so-called "resting" GFR), and/or the renal functional reserve and the GFR impairment induced by salt depletion, in order to understand the role of both "resting" GFR and RFR in the degree of renal dysfunction induced by salt depletion. In control conditions the i.v. infusion of AA + D significantly increased RPF (+ 41% vs. baseline period) with a mean absolute increase of 211 ml/min. A similar pattern was observed in GFR behavior (+31.5% with 34 ml/min of mean absolute increase). A significant inverse exponential relationship was observed between GFR before AA + D i.v. infusion ("resting" GFR) and renal functional reserve (P less than 0.05), suggesting that, in normal conditions, these inversely related parameters may widely vary according to the tone of the glomerular arterioles. Following salt depletion, we observed a variable degree of GFR impairment. Both GFR and RPF were significantly decreased (-25.9%, P less than 0.05 and -29%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)