Monosomy 15 in chronic myelomonocytic leukemia. description of a case and review of the literature

We report a 89-year-old female diagnosed with chronic myelomonocytic leukemia (CMMoL) presenting with a monosomy 15. To our knowledge, this is the second reported case of CMMoL with monosomy 15. On the other hand, monosomy 15 in complex karyotypes is a frequent chromosome aberration in myelodysplastic syndromes, particularly in refractory anemia with excess of blasts.     

Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome

Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.     

Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group‐ and strain‐specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross‐reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains. J. Med. Virol. 69:579–587, 2003. © 2003 Wiley‐Liss, Inc.     

Visual and Hearing Impairment Are Associated With Delirium in Hospitalized Patients: Results of a Multisite Prevalence Study

ObjectiveSensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium.DesignCross-sectional study nested in the 2017 “Delirium Day” project.Setting and ParticipantsPatients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy.MethodsDelirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters).ResultsA total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2–2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1–1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6–1.2, P = .36; OR 1.1; CI 0.8–1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6–1.2, P = .27; OR 1.1, CI 0.8–1.4, P = .63).Conclusions and implicationsOur findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.     

Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.     

Early onset cerebellar ataxia and preservation of tendon reflexes: clinical phenotypes associated with GAA trinucleotide repeat expanded and non-expanded genotypes

The aim of this study was to determine phenotypie characteristics of patients with early onset cerebellar ataxia (EOCA) with preserved tendon reflexes. The series comprises 25 patients, representing 10% of all ataxic patients who have been genetically studied in our laboratory since 1990. There were 11 males and 14 females. Fourteen patients were homozygous for the GAA expansion on chromosome 9q13 (group 1) and therefore a diagnosis of Friedreich's ataxia with retained reflexes (FARR) was given. The remaining 11 patients had two normal non-expanded alleles (group 2) and a working diagnosis of EOCA with retained reflexes (EOCARR) was established. Mean ages of onset were 13.7 +/- 5.9 years (3-25) for group 1 and 10.3 +/- 7.3 for group 2; the difference was not significant. Frequencies of symptoms and signs were also comparable for both groups the only significant differences being the higher frequency of nystagmus, cardiomyopathy and sensory neuropathy in group 1 patients. There was a tendency for FARR patients to have higher frequencies of hypopallesthesia in the lower limbs and skeletal deformities. In none of the cases diabetes mellitus was observed. We conclude that differentiation of FARR and EOCARR may be suspected by classical clinical and electrophysiological data and confirmed by analysis of the GAA repeat.     

Modulation of serotonergic function in rat brain by VN2222, a serotonin reuptake inhibitor and 5-HT1A receptor agonist.

VN2222 (1-(benzo[b]thiophen-3-yl)-3-[4-(2-methoxiphenyl piperazin-1-yl]propan-1-ol) is a potential antidepressant with high affinity for the serotonin transporter and 5-HT(1A) receptors. Locally applied, VN2222 enhanced the extracellular 5-hydroxytryptamine (5-HT) concentration (5-HT(ext)) in rat striatum to 780% of baseline whereas its systemic administration (1-10 mg/kg s.c.) reduced 5-HT(ext). In the presence of citalopram, 8-OH-DPAT or VN2222 applied in medial prefrontal cortex reduced 5-HT(ext). Fluoxetine, VN2222, and 8-OH-DPAT suppressed the firing rate of dorsal raphe 5-HT neurons (ED(50): 790, 14.9, and 0.8 microg/kg i.v., respectively). These effects were antagonized by WAY 100635. Administration of VN2222 for 2 weeks desensitized 5-HT(1A) receptors as assessed by microdialysis and single-unit recordings (ED(50) values for 8-OH-DPAT were 0.45 and 2.34 microg/kg i.v. for controls and rats treated with 6 mg/kg day VN2222). These results show that VN2222 is a mixed 5-HT reuptake inhibitor/5-HT(1A) agonist that markedly desensitizes 5-HT(1A) autoreceptors. These properties suggest that it may be a clinically effective dual action antidepressant drug.     

Clinical evaluation of the simultaneous determination of tumor markers in fluid and serum and their ratio in the differential diagnosis of serous effusions.

We evaluated the diagnostic utility of simultaneous determination of 5 tumor markers, CEA, CA 125, CA 15-3, CA 19-9 and cytokeratin 19 (CYFRA 21-1), in fluid and serum from 101 patients, 52 with pleural effusion (22 malignant) and 49 patients with ascites (14 malignant). Tumor marker concentrations in fluid from patients with malignant effusions were significantly higher than those obtained in benign fluids or serum. However, there are two types of tumor markers: those released/secreted by normal mesothelia such as CA 125 and cytokeratin 19 (higher levels in benign fluids than in serum) and non-released/secreted tumor markers (low concentrations in benign fluids) such as CEA, CA 19-9 and CA 15-3. The fluid/serum (F/S) ratio showed better sensitivity with maximum specificity than a single determination in fluid for CEA, CA 15-3 and CA 19-9, but not for CA 125 and CYFRA. The combination of a F/S ratio greater than 1.2 and a cut-off of 5 ng/ml for CEA, 30 U/ml for CA 15-3 and 37 U/ml for CA 19-9 showed sensitivities of 58, 57 and 44%, respectively, and a specificity of 100%, with a combined sensitivity of 82% for overall effusions and 79% for fluids with negative cytology with a specificity of 100%. In conclusion, the use of the F/S ratio in nonsecreted tumor markers such as CEA, CA 19-9 and CA 15-3 improve the sensitivity and specificity and allow standardization of the cut-off.     

Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia.

PURPOSE: To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We analyzed the outcome of patients who underwent SCT according to their VH mutational status. RESULTS: Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01). CONCLUSION: These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL.