Clinical presentation and differential diagnosis of dementia with Lewy bodies: a review.

BACKGROUND: Dementia with Lewy bodies is one of the most prevalent dementia diagnoses. However, differential diagnosis between dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease with dementia can still be very difficult given the overlap in neuropathology, clinical presentation, cognitive, and neuroanatomical changes. METHOD: A literature review of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease with dementia was conducted using PubMed. RESULTS AND IMPLICATIONS: Accurate diagnosis of dementia with Lewy bodies is crucial in order to more accurately predict the progression of the disease and negative side effects from pharmacological treatment. The differences and similarities between dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease with dementia are highlighted in order to aid clinicians in differential diagnosis.

Urine pentamidine as an indicator of lung pentamidine in patients receiving aerosol therapy.

To determine if urine pentamidine was reflective of lung pentamidine, we compared levels of the drug in bronchoalveolar lavage fluid and simultaneously obtained urine. Thirty-one patients who were receiving aerosolized pentamidine either as treatment or as prophylaxis underwent BAL and submitted urine samples for pentamidine analysis. Pentamidine was analyzed in both phases of BAL fluid (supernatant and cell pellet) and in urine using high performance liquid chromatography. Urine results were normalized for creatinine. Patients were categorized as prophylaxis failures (active Pneumocystis carinii pneumonia on prophylaxis), electives (free from PCP on prophylaxis), treatment (daily AP in treatment doses for active PCP, or miscellaneous (single dose of AP). Levels in BAL fluid and urine varied widely over several orders of magnitude. However, for all patients, we found a highly significant relationship between BAL supernatant and urine (r = 0.97, p less than 0.0001). No statistical differences were found when comparing levels of pentamidine between failures and electives; however, the number of failures was small. We conclude that urine pentamidine is related to lung pentamidine and can be used as a clinical indicator in patients receiving aerosolized therapy.

Tracheal aspirates in long-term mechanically ventilated patients. A human model of gram-negative infection and airway inflammation.

It is well known that patients requiring long-term mechanical ventilation and tracheostomy have nearly universal airway colonization with Gram-negative organisms. However, useful parameters to objectively describe the airway inflammation associated with airway instrumentation and colonization have not been well define. In our respiratory care unit, patients who are medically stable except for ventilator dependence are readily available for longitudinal assessment of airway secretions and therefore provide a unique population for studying airway inflammation and infection. To quantitate production of respiratory secretions, we instituted a uniform protocol of suctioning over a 6-h period. Further, we devised a method of dilution and homogenization of tracheal aspirates that permits reproducible intrasample total cell counts (coefficient of variation, 4.6%). With these techniques, patients were then studied serially over a 4- to 7-week period. Total cell count, inflammatory cell differential, and two indices of airway inflammation, human neutrophil elastase (HLE) and soluble-intercellular adhesion molecule-1 (sICAM-1) studied in the sol phase of secretions were monitored. The mean total cell count was 42.2 x 10(6) cells per gram of secretions when patients were clinically stable and not receiving antibiotics. The average differential was neutrophils 69.9%, macrophages 26.9%, and lymphocytes 2.8%. Mean active HLE was 35.6 micrograms/mL and mean sICAM-1 was 83 ng/mL. Six patients during the period of observation received intravenous oral or aerosolized antibiotics for tracheobronchitis. A threefold drop in volume of secretions was measured (p < 0.018). The total cell count and percent neutrophils decreased from 76.4 x 10(6)/g of sputum to 54.9 x 10(6) and 72.2 to 54.9%, respectively. While these changes were not statistically significant, the absolute number of airway neutrophils over the 6 h decreased sevenfold (p < 0.014). Similarly sICAM-1 burden (micrograms per 6-h period) also decreased significantly (p < 0.034). These patients provide a unique human model for future studies specifically designed to assess the effect of novel modalities of anti-inflammatory and antimicrobial agents on respiratory secretions.

Effect of corticosteroid treatment on hemopoiesis in vivo and in vitro in a patient with Felty's syndrome.

We have studied the CFU-GM and BFU-E in vitro growth in a neutropenic and anemic patient with Felty's syndrome, either before or one and three months after steroid therapy when neutrophils and erythrocytes returned to normal. Both CFU-GM growth and CSA production were found to be low before therapy, and prednisone was shown to raise them to normal levels. The in vitro growth of BFU-E and the production of BPA by T lymphocytes of the patient were significantly lower than normal when studied before therapy. However, the T lymphocytes incubated in vitro with hydrocortisone regained their ability to stimulate the BFU-E growth. After prednisone therapy both BFU-E growth and BPA production by T lymphocytes returned to normal. Possible pathogenetic mechanisms of impaired granulo- and erythropoiesis in Felty's syndrome are discussed. The in vitro study with hydrocortisone can help to identify steroid-sensitive patients.

Alterations of erythropoiesis in chronic uremic patients treated with intermittent hemodialysis.

The in vitro growth of the blood burst-forming cells (BFU-E) of 9 chronic uremic patients, treated with intermittent hemodialysis three times a week has been studied at the time of maximum and minimum level of retained nitrogen catabolites. The effect of uremic sera on the vitro growth of normal BFU-E was also studied. The in vitro growth of blood BFU-E was shown to be greatly reduced in all uremic patients and dialysis did not modify their growth. The sera of uremic patients significantly inhibited the in vitro growth of normal blood BFU-E when it was taken at the time of maximum retention of nitrogen catabolites. However, inhibition of normal BFU-E growth was not seen when uremic sera were taken at the time of minimum retention of nitrogen catabolites. These data seem to indicate a long lasting suppression of BFU-E in chronic uremia due to serum inhibitor/s.

In vitro growth of erythroid progenitor cells (BFU-E) and production of burst-promoting activity (BPA) by T lymphocytes in patients with myelodysplastic syndromes.

The in vitro growth of circulating erythroid progenitors (BFU-E) populations and the production of burst-promoting activity (BPA) by T lymphocytes have been studied in 17 patients with myelodysplastic syndromes. Based on the in vitro growth patterns of BFU-E, four groups of patients have been identified: i) normal BFU-E growth; ii) low spontaneous BFU-E growth, but normal response to LCM; iii) impaired BFU-E response to LCM; iv) no BFU-E growth. The pattern of BFU-E growth seems to be related to the clinical stage of the disease rather than to the FAB subgroup to which the patients belong. The ability of T lymphocytes to stimulate BFU-E growth was significantly reduced in all patients. The possible mechanisms inducing the impaired production of BPA by T lymphocytes are discussed. The in vitro evaluation of circulating erythroid precursors can supply useful prognostic information and possibly indications concerning the responsiveness of erythropoietic stem cells to recombinant human erythropoietin in vivo.

T lymphocyte subsets in chronic uremic patients treated with maintenance hemodialysis.

Blood T lymphocyte subsets have been studied using monoclonal antibodies in 10 chronic uremic patients treated with maintenance hemodialysis. Both total T lymphocytes identified by the antibody OKT3, and the helper-inducer T lymphocyte subset identified by the antibody OKT4 were found to be significantly lower than normal. The cytotoxic-suppressor T cell subset was only moderately, even if significantly reduced, so that the T4/T8 ratio in uremic patients was significantly lower than normal. These data provide an additional contribution to the interpretation of immunological and hematological deficiencies observed in chronic uremia.

Defective in vitro growth of BFU-E of elderly subjects revealed by hydrocortisone.

The effect of aging on hematopoiesis and bone marrow exhaustion have long been debated. Unexplained anemia and impaired in vitro proliferation of erythroid precursors is frequently observed in the elderly. As hydrocortisone is known to increase the BFU-E in vitro growth, we have studied the response of BFU-E to hydrocortisone in a group of nonanemic elderly subjects. The BFU-E growth in methylcellulose from blood mononuclear cells (MNC), stimulated by lymphocyte-conditioned medium (LCM), either with or without hydrocortisone, of 10 subjects aged 76-91 years was compared with the BFU-E growth from MNC of a group of ten young subjects. While LCM induced a significant increase of BFU-E growth, both in young and old subjects, hydrocortisone induced a significant increase of BFU-E growth only in young subjects. This study shows that in the elderly, there is a latent defect of erythropoiesis, possibly consisting of a defective ability to modulate the receptors for erythropoietin on BFU-E, and that hydrocortisone offers a useful tool to identify it.

Correlation between blood granulocyte progenitor cells and polymorphonuclear leukocytes. A tentative pathophysiological subgrouping of neutropenic and neutrophilic patients.

Blood granulocyte-macrophage progenitors (CFU-GM) were studied in 116 normal, 32 neutropenic and 22 neutrophilic subjects through a double layer agar culture system. The neutropenic group showed significantly lower than normal mean value of CFU-GM per ml of blood, the blood concentration of CFU-GM being within normal limits in 25/32 subjects (78.1%). The neutrophilic group showed significantly higher than normal mean value of blood CFU-GM, and a normal blood concentration of CFU-GM was found in 17/22 patients (77.3%). Within the neutropenic group the concentration of blood CFU-GM was lower than normal in 5/11 (45.4%) patients with less than 1.1 x 10(9) polymorphonuclear leukocytes (PMN) and only in 2/21 (9.5%) patients with more than 1.1 x 10(9)/1 PMN. Within the neutrophilic group the concentration of blood CFU-GM was normal in all 12 subjects having less than 10.5 x 10(9)/1 PMN, while 5/10 (50%) patients with more than 10.5 x 10(9)/1 PMN had higher than normal blood concentration of CFU-GM. The mean leukocyte CSA of the normal, neutropenic and neutrophilic groups did not differ significantly. Within the neutropenic group the CSA was lower than normal in 3/11 (27%) patients with less than 1.1 x 10(9)/1 PMN and in 2/20 (10%) patients with more than 1.1 x 10(9)/1 PMN. Within the neutrophilic group the CSA was normal in all patients with less than 10.5 x 10(9)/1 PMN and it was higher than normal in 2/10 (20%) patients with more than 10.5 x 10(9)/1 PMN. A pathophysiological approach to both neutropenia and neutrophilia, according to PMN and CFU-GM blood concentration, is discussed.

Comparison between diurnal changes and changes induced by hydrocortisone and epinephrine in circulating myeloid progenitor cells (CFU-GM) in man.

A significant increase from 8 AM to 3 PM was found in both myeloid progenitor cell (CFU-GM) and polymorphonuclear leukocyte (PMN) blood concentration in 45 normal subjects. Diurnal blood (CFU-GM and PMN changes were significantly correlated. Spontaneous diurnal changes in blood CFU-GM levels and in PMN were compared with the changes induced by i. v. administration of hydrocortisone (16 normal volunteers) and of epinephrine (10 normal volunteers). Diurnal changes in CFU-GM and PMN seem to follow a pattern similar to that induced by epinephrine administration. These findings suggest that diurnal changes in CFU-GM reflect mainly a shift of these cells between different blood compartments.

[Evaluation of antibody specificity of the monoclonal component in a case of Waldenström's macroglobulinemia]. / Valutazione della specificità anticorpale della componente monoclonale in un caso di macroglobulinemia di Waldenström.

The antibody specificity of the monoclonal component was studied in a patient with Waldenström's macroglobulinemia who presented with high values of antistreptolysin O (ASO) titer and protein C which are clinical unlikely. Our methods demonstrated that two tests were falsely positive, inasmuch as the antibody activity of the monoclonal component was directed towards the albumin plus latex complex which theoretically is an inert immunological substrate.

[Transient loss of consciousness: a frequent and difficult problem in emergency service. Retrospective analysis of 391 cases]. / Perdita transitoria di coscienza: un frequente e difficile problema nel pronto soccorso. Analisi retrospettiva di 391 casi.

The present study was designed to evaluate the patients with transient loss of consciousness who are seen in the emergency room and the ways in which they are currently triaged and evaluated, to determine the risk factors influencing their prognosis, and to analyze the aspects of diagnostic evaluation that are most useful. We made a retrospective study of 391 patients with transient loss of consciousness seen at the emergency room of S. Martino hospital. The causes of loss of consciousness, admission decision, diagnostic tests ordered, initial and final diagnoses and mortality are evaluated. The admission decision was influenced by three factors: cause of loss of consciousness, presence of chronic disease, and patient age. The same factors were shown to influence mortality. Full concordance between initial and final diagnosis was only 50 per cent. In 18.6 per cent of patients the cause of loss of consciousness was not identified at dismissal. The history and physical examination were crucial elements in the evaluation of most patients, and only in selected cases did tests such as electrocardiogram, Holter monitoring, electroencephalogram, computerized tomography scan provide diagnostic information.

[Surgical treatment of biliary lithiasis associated with acquired valvulopathy]. / Il trattamento chirurgico della litiasi biliare associata a valvulopatie acquisite.

Personal experience in the treatment of acquired valvulopathies and biliary calculosis in one operating stage is reported. After examination the risk factors determining onset of bile calculosis in valvulopathic patients, the surgical techniques adopted and the special advantages obtained by associating the two operations at the same session are illustrated.

[Question of differential diagnosis in a case of chronic B-cell lymphopathy]. / Quesiti diagnostico-differenziali su un caso di linfopatia cronica di origine B cellulare.

We have reported the case of a woman aged 76 years suffering from pancytopenia, splenomegaly, relative lymphocytosis, lymphocytes with villous projection in the peripheral blood. On the basis of membrane phenotype, cytochemistry, ultrastructural examination of blood and marrow lymphocytes, differential diagnosis was between chronic lymphatic leukemia (CLL), CLL of mixed cell type, hairy cell leukemia (HCL), HCL variant, splenic lymphoma with circulating villous lymphocytes (SLVL), Non-Hodgkin lymphoma of mantle zone (NHL). The application of morphologic and immunological methods has reinforced the value of cytomorphology and has proved advantageous in increasing our understanding of the heterogeneity of B CLL itself. A new classification of chronic B leukemias has been proposed on the basis of clinical, cytomorphological, histological, cytochemical, immunological criteria: CLL; CLL of mixed cell type including cases with more than 10% and less than 55% prolymphocytes (CLL/P) and a less well defined form with pleomorphic lymphocytes (CLL/P) and a less well defined form with pleomorphic lymphocytes but less than 10% prolymphocytes; prolymphocytic leukemia (PLL); hairy cell leukemia (HCL); HCL variant; splenic lymphoma with circulating villous lymphocytes (SLVL); leukemic phase of NHL (follicular lymphoma, intermediate or mantle zone lymphoma, and others); lymphoplasmacytic lymphoma; plasma cell leukemia. Even if the application of cytomorphological and immunological criteria has increased our knowledge of the heterogeneity of chronic B leukemias, in some cases, as in the one reported, exact classification may be very difficult. However, on the basis of clinical and laboratory criteria this case can be classified as SLVL, notwithstanding some discrepancies of the immunophenotype.

[Anthracyclines and the heart]. / Le antracicline e il cuore.

Cardiotoxicity is the most important side effect of the highly effective chemotherapeutic drugs anthracyclines. The total dose that must not be surpassed to avoid cardiotoxicity is specific for each anthracycline. For doxorubicin the maximal dose is 450-550 mg/mq. Nevertheless cardiotoxicity can be observed in some cases even with doses smaller than the critical ones. Clinical signs of cardiotoxic damage can appear at any stage during the course of therapy. The prevention of cardiac damage can be tried in three ways. Firstly one should extend the administration period of the total dose of the drug for about 6 hours. The second way is based on the use of anthracycline analogs less toxic and possibly equally effective than doxorubicin. Finally one can associate to the anthracycline a cardioprotective drug such as ICRF187. The diagnosis of cardiotoxicity is usually reached evaluating the reduction of left ventricular ejection fraction either with echocardiography or with angiocardiography. Other parameters, particularly those evaluating the diastolic function, are under study to make the diagnosis more quick and accurate. Both cardiac scintigraphy and tomography also seem to offer promising tools for the diagnosis of anthracycline cardiotoxicity. Endomyocardiac biopsy is highly effective for the diagnosis, but is indicated only for selected cases. The therapy of anthracycline cardiomyopathy is directed mainly to the control of congestive heart failure. In the initial phase the treatment is based on the use of digitalis and diuretics, that are substituted in the following maintaining phase by ACE inhibitors.

[Recent findings on the pathogenesis and therapy of anemia in chronic kidney failure]. / Recenti acquisizioni sulla patogenesi e terapia dell'anemia dell'insufficienza renale cronica.

Recent studies showed that the blood BFU-E, when subtracted from the uremic milieu, normally responds to the stimulating factor produced by T lymphocytes. The serum of uremic patients inhibits the in vitro growth of normal BFU-E, however, the inhibition is almost completely reversed by hemodialysis. These data allow to understand why the therapy with erythropoietin relieves the anemia of CRF. Uremic T lymphocytes fail to stimulate the BFU-E growth. Normal T lymphocytes are inhibited by uremic serum and the hemodialysis does not correct the defect. Lymphopenia, decreased number of both T4 and T8 lymphocytes and low T4/T8 ratio were found in 50% of patients. Cimetidine was still able to increase the burst-stimulating activity of uremic T lymphocytes through inhibition of the suppressor T subset. In conclusion, one can say that in CRF T8 lymphocytes are normal and that uremic toxins decrease both number and function of T4 lymphocytes. The deficiency of BPA appears to significantly contribute to the pathogenesis of the anemia of CRF. The experience from our and other Institutions shows the effectiveness of the recombinant human erythropoietin in relieving the anemia of CRF, notwithstanding the hematological milieu is highly modified by uremia.

The similar effects of verbal and non-verbal intervening tasks on word recall in an elderly population.

Vulnerability to retroactive interference has been shown to increase with cognitive aging. Consistent with the findings of memory and aging literature, the authors of the California Verbal Learning Test-II (CVLT-II) suggest that a non-verbal task be administered during the test's delay interval to minimize the effects of retroactive interference on delayed recall. The goal of the present study was to determine the extent to which retroactive interference caused by non-verbal and verbal intervening tasks affects recall of verbal information in non-demented, older adults. The effects of retroactive interference on recall of words during Long-Delay recall on the California Verbal Learning Test-II (CVLT-II) were evaluated. Participants included 85 adults age 60 and older. During a 20-minute delay interval on the CVLT-II, participants received either a verbal (WAIS-III Vocabulary or Peabody Picture Vocabulary Test-IIIB) or non-verbal (Raven's Standard Progressive Matrices or WAIS-III Block Design) intervening task. Similarly to previous research with young adults (Williams & Donovick, 2008), older adults recalled the same number of words across all groups, regardless of the type of intervening task. These findings suggest that the administration of verbal intervening tasks during the CVLT-II do not elicit more retroactive interference than non-verbal intervening tasks, and thus verbal tasks need not be avoided during the delay interval of the CVLT-II.

Normal aging and cognition: the unacknowledged contribution of cerebrovascular risk factors.

Despite the widespread assumption that cognitive decline is an inherent part of the normal aging process, research suggests that part of the variance in age-related cognitive decline is attributable to modifiable factors common in geriatric populations such as cerebrovascular risk factors. We completed a literature search using Science Citation Index and evaluated the most cited articles from the last 10 years to determine the extent to which investigations of normal aging and cognition account for the influence of cerebrovascular risk factors. We found that the majority of the most frequently cited literature does not adequately account for the contribution of cerebrovascular risk factors and therefore, it is possible that many conclusions about normal aging and cognition are flawed or incomplete. Further investigation of the role of cerebrovascular risk factors in age-related cognitive decline is imperative to more accurately understand the effect of aging on cognition.

Intervening tasks and visuospatial memory: the role of similarity in retroactive interference.

Verbal tasks are often administered during the Rey-Osterreith Complex Figure Test (ROCFT) delay period in order to minimize retroactive interference resulting from similarity between tests (Meyers & Meyers, 1995). However, previous studies showed that similarity between the California Verbal Learning Test-II (CVLT-II) and intervening tasks administered during the delay period did not affect memory performance on the CVLT-II. In the current study we examined whether intervening tasks similar to the ROCFT would increase retroactive interference compared to dissimilar tasks, thereby negatively impacting visuospatial memory performance. A total of 106 undergraduate students were divided into three groups. Each group completed different intervening tasks during the ROCFT delay interval. Groups did not differ on copy, immediate recall, and delayed recall trials of the ROCFT. However, a repeated-measures ANOVA revealed an interaction between group and trial (p < .001), suggesting group performance on the ROCFT was differentially impacted by the intervening task. Planned comparisons indicated that the group completing two similar non-verbal intervening tasks had poorer memory of the complex figure and performed significantly worse on recognition (p = .003) and percent retention (p < .001) trials, respectively. This suggests that similarity of intervening tasks impacts memory performance on a complex figure test.