No evidence for a genetic relationship between Alzheimer's disease and longevity

OBJECTIVE: Late onset Alzheimer's disease (AD) is frequent in subjects who have reached an age above the average life expectancy. AD and life expectancy are both influenced by genetic factors. Consequently, a possible genetic relationship between AD and longevity was investigated using family study data. METHODS: First-degree relatives of patients with AD (n = 645) and of non-demented controls (n = 1,106) were examined by direct interview or by family history in the case of already deceased or unavailable subjects. Survival of subjects with an assumed familial load for AD (i.e. first-degree relatives of AD patients) and of controls was compared using the Kaplan-Meier analysis and log-rank statistics. RESULTS: Relatives with AD reached higher ages than other family members. However, there was no significant co-aggregation of AD and longevity in first-degree relatives of AD patients in comparison with those of controls. This applied to all diseased as well as non-demented relatives. CONCLUSIONS: Longevity is an independent prerequisite for the development of the disease, but is not genetically related to AD. The apparent longevity in relatives with AD is likely to result from the selection of subjects fulfilling this prerequisite.     

Functional properties of neuronal nicotinic acetylcholine receptors in the chick retina during development

Acetylcholine (ACh) has been recognized for a long time as a major neurotransmitter in the retina, however, little is known about the contribution of acetylcholine receptors in synaptic processing. Moreover, even less information is available concerning their role during development. To address this question further, we examined the physiological and pharmacological properties of neuronal nicotinic acetylcholine receptors (nAChRs) in retinal ganglion cells from embryonic (E) 12-18-day-old Leghorn chicks. Patch-clamp recordings in whole-cell configuration revealed that at E12 approximately 21% of the ganglion cells responded to acetylcholine pulses with inward currents. The number of responsive cells progressively increased to 57% at E15 to reach up to 15 positive cells out of 15 cells tested at E18. Acetylcholine-evoked responses could be subdivided, according to their time course, into fast and slowly desensitizing. Taking advantage of the selectivity of the frog toxin epibatidine (Epi), that preferentially activates heteromeric neuronal nicotinic acetylcholine receptors, we compared the currents evoked by this toxin vs. the effects of acetylcholine. A further characterization of the receptor diversity during development was to assess their sensitivity to the alpha-conotoxin MII (alpha-CTX-MII), which has been shown to preferentially block alpha6- and alpha3beta2-containing receptors. These data demonstrate that ganglion cells of the chick retina express multiple receptor subtypes that progressively develop as a function of retina maturation.     

On-site evaluation of percutaneous CT-guided fine needle aspiration of pulmonary lesions. A study of 321 cases

PURPOSE: The aim of this study was to assess the usefulness of having a cytopathologist present during percutaneous CT-guided fine needle aspiration (FNA) of pulmonary lesions. MATERIALS AND METHODS: Three hundred and twenty-one FNAs of lung lesions were performed in 312 patients (218 males, 94 females; age range: 20-86 years; mean age: 66 yrs). Nodule sizes ranged from 0.5 to 8 cm. The sampling was performed by a radiologist under CT-guidance; the calibre of the needle used was 20-25 G. Smears were prepared in the Radiology Department and stained using a quick method by a cytopathologist: the sample adequacy was assessed and, if possible, a preliminary diagnosis was made. An additional FNA was requested if the first aspirate was considered diagnostically inadequate. The diagnostic accuracy was examined by reviewing the clinical data and by correlating with the histological material and the clinical outcome. RESULTS: Satisfactory diagnostic material was obtained in 275 of the 321 FNA (86%): 231 were malignant (72%), 8 suspicious (3%) and 36 were negative for malignancy (11%). Forty-six of the 321 specimens (14%) were considered inadequate for any diagnostic verification. An additional FNA was performed immediately in 60 cases (19%). Forty-two subjects developed pneumothorax: 21 patients (50%) of these required thoracic drainage. Blood effusion around the lesion site or adjacent to the needle path was observed in 39 patients (12%). Sensitivity was 99%, specificity was 95% and diagnostic accuracy was 99%. CONCLUSIONS: CT guided aspiration cytology can be a safe and fast procedure for lung nodule characterisation. On-site immediate evaluation of FNA specimens can be beneficial in determining the adequacy of the aspirate and in providing accurate preliminary diagnoses of the specimens, thus allowing for rapid clinical decisions.     

Prognostic factors for transformation in asymptomatic immunoglobulin m monoclonal gammopathies

We evaluated the risk of transformation of asymptomatic immunoglobulin (Ig) M monoclonal gammopathy (aIgM-MG) into symptomatic lymphoproliferative disease in 384 patients, in subgroups of patients with IgM MG of undetermined significance (MGUS) and smoldering Waldenstrom's macroglobulinemia (sWM). One hundred seventy-two patients with aIgM-MG with bone marrow (BM) histopathology and immunophenotyping were available for analysis. After a median of 45 months (range, 12-233 months), 45 cases of aIgM-MG (11.7%) evolved into lymphoproliferative disease, as follows: symptomatic WM (n = 41), non-Hodgkin's lymphoma (NHL; n = 2), IgM multiple myeloma (IgM-MM; n = 1), and primary amyloidosis (n = 1). Cumulative transformation probability at 5 and 10 years was 8% and 29%, respectively. The parameters significantly correlated with evolution were, at univariate analysis, BM lymphoplasmacytic infiltration, high erythrocyte sedimentation rate, hemoglobin (Hb) level, IgM size, and peripheral lymphocytosis; at multivariate analysis, the parameters were IgM size and peripheral lymphocytosis, with Hb level associated with a trend toward higher progression risk. Of the 138 cases of IgM-MGUS, 14 (10.1%) evolved (13 WM, 1 IgM-MM) after a median of 75 months (range, 12-117 months); of the 34 cases of sWM, 13 (38.2%) progressed to WM after 55 months (range, 13-154 months). In patients with IgM-MGUS, event-free survival at 5 and 10 years was 95% and 83%, respectively, and in patients with sWM, 77% and 42%, respectively (P = 0.0001). Among patients with aIgM-MG, those at high risk of evolution are patients with sWM, a distinct entity with clear BM evidence of NHL.     

Bone marrow CD34+ cell count is predictive for adequate peripheral progenitor cell collection

Several studies have investigated the influence of clinical and biological variables on mobilisation of peripheral blood progenitor cells (PBPCs). The aim of this study was to evaluate the role of steady-state bone marrow (BM) CD34+ cells as a predictive parameter of PBPC yield. We studied 90 patients with multiple myeloma (MM) (41 patients), non-Hodgkin's lymphoma (NHL) (25 patients) or acute myeloid leukaemia (AML) (24 patients), mobilised with chemotherapy and growth factor. The median time from first treatment to mobilisation was 5 months. Only one patient was previously exposed to alkylating agents. The median BM CD34+ count at mobilisation was 833 microl(-1) (range: 1.4-15.540) corresponding to 1.51% of mononuclear cells (range: 0.02-8.6). Sixty-six patients (73%) reached the optimal target of 4 x 10(6) kg(-1) CD34+ cells with 1 (18 patients), 2 (42 patients) or 3 leukaphereses (6 patients). Eleven patients (12%) mobilised less than 4 x 10(6) kg(-1) CD34+ cells and 13 (15%) failed mobilisation. Among the laboratory and clinical parameters evaluated at the time of mobilisation, only BM CD34+ count was a predictive factor for adequate collection (P = 0.04), particularly in MM patients (P = 0.003). In this setting, a BM concentration of CD34+ cells lower than 66 microL(-1) was associated with a higher probability of inadequate collection.     

A breast cancer patient from Italy with germline mutations in both the BRCA1 and BRCA2 genes

We report the first case in Italy of a non-Ashkenazi double heterozygote for BRCA1 and BRCA2 genes. This finding is predictably rare, with a maximum frequency of 1/250,000. The proband and her mother were diagnosed with early-onset breast cancer. No other relatives with breast and/or ovarian cancer were observed. The implications of this case in regard to genetic testing and counseling are substantial.     

Study of sunbathing in children: the preliminary evaluation of a prevention program

AIMS AND BACKGROUND: Sunburn during childhood is associated with an increased risk for developing melanoma in an adult age. The aim of the present study was to define the validity of our educational program in order to teach the positive effects and risks of sun exposure during childhood. PATIENTS AND METHODS: We conducted a population-based, case-control study in primary schools of three towns in Northern Italy (Brescia, Bergamo and Trento) between 2001 and 2002. The study was carried out on 1945 pupils (aged 8-9 years) and included 1309 case children who received an educational program before the summer to increase awareness towards sun exposure and 636 control children who did not. Parents of case and control children were interviewed using a questionnaire about their children's skin characteristics, sun protective behavior and sunburns. The questionnaire was completed twice, before and after the summer, to verify the changes of sun exposure habits. RESULTS: A significant decrease in sunburns was demonstrated in the group of subjects who received the educational program, indicating the validity of our operative procedure (from 14.6% to 10%, P = 4 x 10(-4). CONCLUSIONS: Our educational melanoma program may be important to disseminate in a wider range of children a correct education on sun exposure during childhood.     

Diagnostic approach to a persistent anterior knee pain

The case of a 67-year-old female patient with persistent pain in the right anterior knee appeared after she had an accidental fall, is discussed. Laboratory tests and imaging were negative. Persistent pain required MRI. Based on MRI findings the diagnosis of patellar fracture responsible for knee pain could be established.     

Severity of intraoperative tricuspid regurgitation predicts poor late survival following cardiac transplantation

Background

This study evaluates the significance of tricuspid regurgitation (TR) on long-term survival as detected by intraoperative transesophageal echocardiography at the time of orthotopic heart transplantation. Although significant (2+ to 4+) TR after orthotopic heart transplantation is rare, its influence on long-term survival is unknown, warranting further investigation.

Methods

Between January 1992 and July 2001, 181 consecutive patients underwent orthotopic heart transplantation. Tricuspid regurgitation was graded by intraoperative transesophageal echocardiography after final separation from cardiopulmonary bypass in 130 of 181 patients (72%).

Results

Although 80% (104/130) of patients had either no (0, n = 77) or trace (1+, n = 27) TR, 9% (12/130 patients) had mild (2+), 10% (13/130 patients) had moderate (3+), and 0.8% (1/130 patients) had severe (4+) TR. The severity correlated strongly with the presence of right ventricular dysfunction (p < 0.001). In a multivariate regression model, gender mismatch (p = 0.002) and right ventricular dysfunction (p < 0.001) were independent predictors for equal to or greater than mild (2+ to 4+) TR (p = 0.015). Although the degree of recipient pulmonary vascular resistance did not influence the grade (p = 0.600), higher pulmonary vascular resistance tended to increase the severity of TR in the setting of prolonged donor ischemic times (p = 0.054). Proportional hazards regression analysis demonstrated significantly decreased survival for patients with mild or greater (2+ to 4+) TR detected by transesophageal echocardiography at the time of transplantation (p < 0.001) and RV dysfunction (p = 0.023).

Conclusions

Even mild (≥ 2+) TR identified by transesophageal echocardiography at the time of orthotopic heart transplant predicts poor late survival, suggesting a possible role for concomitant tricuspid valve repair at the time of transplant. Whether or not tricuspid valve repair will improve long-term survival is unknown.