Early motor signs of attention-deficit hyperactivity disorder: a systematic review.

ADHD is a common neurodevelopmental disorder with onset of symptoms typically in early childhood. First signs of the disorder, including language delay, motor delay and temperament characteristics, may be evident as early as infancy. The present review describes published evidence about early motor signs of either children with later symptoms of ADHD or a later diagnosis of the disorder. Nine published cohort studies were included after a systematic search of related terms in PubMed and PsycInfo databases. Study eligibility criteria included: (1) report on early motor function or any motor-related signs; (2) the presence of a participants' assessment by/at 12 months of age; (3) report of a later presence of ADHD symptoms. The limited number of reports included suggests an association between mild early neurological markers and later developmental coordination disorder and motor overflow movements. Unfortunately, due to their small sample sizes and focus on group reports rather than individuals, they have limited power to find strong associations. Early motor indicators of ADHD, if present, appear to be non-specific, and therefore not yet useful in clinical screening. Spontaneous motility seems to be a promising measure for early ADHD detection, although further studies with large cohorts are recommended to determine its clinical role in children at risk for ADHD.

Unmet Needs of Patients with Chronic Respiratory Diseases Within Primary Healthcare.

There is no data on the level of unmet needs in the heterogenic group of chronically ill patients. The purpose of this study was to define the degree of unmet needs in patients with chronic respiratory diseases and to identify the factors that determine them. The study group consisted of 214 adult patients with the median age of 65 (min-max: 18-90 years). Variables affecting the level of satisfied needs were the following: gender, age, marital status, place of residence, number of chronic diseases, somatic symptoms, level of disease acceptance, level of quality of life (QoL), and health behaviors. The prevention program to increase the level of satisfied needs in patients with chronic respiratory diseases, apart from obviously being addressed to those with low levels of health satisfaction and quality of life indices, should be addressed to men, the elderly, those having no partner, living in the countryside, and having multiple somatic symptoms. Patients with a high level of disease acceptance, those maintaining physical quality of life and advantageous health behaviors should be considered as well.

Factors Influencing Utilization of Primary Health Care Services in Patients with Chronic Respiratory Diseases.

The purpose of our study was to determine the factors affecting the level of services provided in primary health care among patients with chronic respiratory diseases. The study group consisted of 299 adults (median age: 65, min-max: 18-92 years) with mixed chronic respiratory diseases, recruited from patients of 135 general practitioners. In the analysis, in addition to the assessment of the provided medical services, the following were used: Patient Satisfaction Questionnaire, Camberwell Assessment of Needs Short Appraisal Schedule, Acceptance of Illness Scale, and WHO Quality of Life Instrument Short Form. Variables that determined the level of services were the following: age, place of residence, marital status, number of chronic diseases, and level of disease acceptance, quality of life, and health behaviors. The level of provided services correlated with variables such as gender, severity of somatic symptoms, level of satisfied needs, and satisfaction with health care. We concluded that in patients with mixed chronic respiratory diseases a higher level of health care utilization should be expected in younger patients, those living in the countryside, those having a partner, with multimorbidity, a low level of disease acceptance, those satisfied with their current quality of life, with positive mental attitudes, and maintaining health practices.

Specific abnormalities versus number of abnormalities and cytogenetic scoring systems for outcome prediction after allogeneic hematopoietic SCT for myelodysplastic syndromes.

Newer cytogenetic scoring systems for myelodysplastic syndromes (MDSs), like cytogenetic stratification of the revised international prognostic scoring system (IPSS-R) or monosomal karyotype, may also improve outcome prediction after hematopoietic SCT (HCT). We compared the prognostic value of specific cytogenetic abnormalities, IPSS-R karyotype and monosomal karyotype for HCT outcome in 98 patients with MDS and AML post MDS. Higher-risk IPSS-R karyotype, 3q21q26 and transformation to AML before HCT were associated with increased cumulative incidence of relapse (CIR), whereas OS was adversely influenced by del 5q/-5, abnormalities of chromosomes 11 and 17 and cytogenetic IPSS-R very poor category. Karyotype with ⩽2 abnormalities and no abnormalities of chromosomes 3, 5, 7, 11 and 17 was an independent prognostic factor of lower CIR (hazard ratio (HR)=0.2, P=0.01) and longer OS (HR=0.5, P=0.03). In conclusion, some specific cytogenetic abnormalities and high cytogenetic complexity, as reflected by IPSS-R very poor karyotype, rather than monosomal karyotype, were associated with higher CIR and shorter OS after HCT. Conversely, results were encouraging in patients lacking those abnormalities, who may be very good candidates for HCT.

The value of expression of EGFR, telomerase and topoisomerase IIα in malignant effusion smears before and after chemotherapy.

PURPOSE: To evaluate the significance of expression of epidermal growth factor receptor (EGFR), telomerase and topoisomerase IIα (topo IIα) in cells of malignant effusions of patients under chemotherapy. METHODS: We studied the expression of EGFR, telomerase and topo IIα in malignant effusion smears of 95 cancer patients before and after chemotherapy. Immunocytochemical and in situ hybridization techniques were applied. RESULTS: Positive expression before chemotherapy of telomerase, topo IIα and EGFR was found in 64.2, 63.2 and 69.5% of the cases, respectively; the expression of these markers following chemotherapy was 43.6, 28.2 and 53.8%, respectively. The stronger prognostic factor affecting survival before chemotherapy was telomerase (p=0.0002), whereas after chemotherapy the strongest factor was EGFR (p<0.0001). A positivity for all three markers following chemotherapy was associated with shorter survival compared with positivity for only 1 or 2 markers (p<0.0001) or with a negative expression. CONCLUSION: It seems that expression of EGFR, telomerase and topo IIα in malignant effusion smears is adversely affecting prognosis and survival.

Molecular evidence for EBV and CMV persistence in a subset of patients with chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors.

The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is uniquely characterized by the presence of stereotyped B-cell receptors (BCRs). A major BCR stereotype in CLL is shared by immunoglobulin G-switched cases utilizing the immunoglobulin heavy-chain variable 4-34 (IGHV4-34) gene. Increased titers of IGHV4-34 antibodies are detected in selective clinical conditions, including infection by B-cell lymphotropic viruses, particularly Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In this context, we sought evidence for persistent activation by EBV and CMV in CLL cases expressing the IGHV4-34 gene. The study group included 93 CLL cases with an intentional bias for the IGHV4-34 gene. On the basis of real-time PCR results for CMV/EBV DNA, cases were assigned to three groups: (1) double-negative (59/93); (2) single-positive (CMV- or EBV-positive; 25/93); (3) double-positive (9/93). The double-negative group was characterized by heterogeneous IGHV gene repertoire. In contrast, a bias for the IGHV4-34 gene was observed in the single-positive group (9/25 cases; 36%). Remarkably, all nine double-positive cases utilized the IGHV4-34 gene; seven of nine cases expressed the major BCR stereotype as described above. In conclusion, our findings indicate that the interactions of CLL progenitor cells expressing distinctive IGHV4-34 BCRs with viral antigens/superantigens might facilitate clonal expansion and, eventually, leukemic transformation. The exact type, timing and location of these interactions remain to be determined.

Report of two novel chromosomal translocations in chronic lymphocytic leukemia.

Two novel chromosomal translocations were identified in 2 patients with chronic lymphocytic leukemia (CLL). Case 1: 60 year-old male, stage Rai 0/Binet A, with mutated immunoglobulin heavy (IgH) and lambda (Iglambda) light chain genes; karyotype: 46, XY, t(9;12)(q12;p11) [3]/ 46, XY [22]. Case 2: 56 year-old male, stage Rai 2/Binet B, with mutated IgH and unmutated Iglambda genes; karyotype: 46, XY, add(10)(q26), t(13;18)(q14;q21) [8]/ 46, XY [27]. Although both translocations are novel, the involved breakpoints (especially 13q14 and 18q21) have been reported to participate in various aberrations in CLL patients. Aberrations affecting bands 9q12 and 12p11, as in case 1, are generally rare.

Therapy-related myelodysplastic syndrome with monosomy 5 and 7 following successful therapy for acute promyelocytic leukemia with anthracyclines.

Myelodysplastic syndrome (MDS) in patients treated for acute promyelocytic leukemia (APL) is a rare event. We describe a patient with APL who developed MDS 40 months after entering complete remission (CR). Karyotypic analysis revealed monosomy 5 and 7, which are cytogenetic changes usually occurring after the use of alkylating agents. The patient had received only anthracyclines as potential leukemogenic drugs. A review of the literature on t-AML/MDS occurring after successful therapy for APL showed three similar cases. These observations suggest that anthracyclines may cause t-AML/MDS similar to that induced by alkylating agents.

Isolated pentasomy of chromosome 8 in erythroleukemia.

Pentasomy 8 as a sole anomaly in hematological disorders is rare. Only 2 such cases, one in acute monocytic leukemia and one in chronic myelomonocytic leukemia have been described in the literature to date. Here, we report the first case of a 42 year old man with erythroleukemia displaying a pentasomy 8 clone. Conventional cytogenetics of bone marrow cells showed 16 metaphases with pentasomy 8 and 9 with normal diploidy. Fluorescence in situ hybridization (FISH) analysis using a whole chromosome painting probe and a centromeric probe specific for chromosome 8 confirmed the presence of pentasomy 8 and also revealed a low percentage of a trisomic and a tetrasomic clone. The patient died three days after diagnosis without chemotherapy. The findings suggest that pentasomy 8 is associated with a heterogeneous group of myeloid disorders and probably plays a specific role in the progression of myeloid neoplasia.

The leading role of hepatitis B and C viruses as risk factors for the development of hepatocellular carcinoma. A case control study.

A double case control study evaluated the role of hepatitis C virus (HCV) and hepatitis B virus (HBV), alcohol drinking, and tobacco smoking as potential risk factors for cepatocellular carcinoma (HCC). Fifty-one patients with HCC, 34 of whom had underlying cirrhosis, were analyzed against 51 hospital controls and 34 patients with cirrhosis, respectively. Sera from patients of all three groups were tested for HBV markers and anti-HCV antibodies. The polymerase chain reaction technique was used to detect HCV RNA in the anti-HCV-positive samples. Alcohol drinking and smoking habits were recorded for all patients. HCC risk was significantly related to the presence of hepatitis B surface antigen (HBsAg) [relative risk (RR) = 18], HCV infection (RR = 8), and alcohol abuse (RR = 4). When the presence of cirrhosis was taken into account, only HBsAg positivity was significantly associated with HCC development (RR = 6.7), indicating that HCV infection and alcohol abuse are related to HCC indirectly through the cirrhotic process. No significant interaction between HCV and HBV infection in the causation of HCC was found. Through the computation of population-attributable risk, it was found that 46% of the HCC cases in Greece could be attributed to HBsAg positivity but only 4% to HCV infection. In conclusion, HBV infection is the major risk factor in the development of HCC in Greece, either by inducing cirrhosis or by direct oncogenic effect. HCV infection is also related to HCC development, albeit indirectly through the cirrhotic process.

Enhanced proliferative response to beta-endorphin of phytohemagglutinin-activated lymphocytes from patients with ulcerative colitis.

We investigated the effect of a known T cell mitogen, phytohemagglutinin (PHA) and the neuropeptide beta-endorphin on the in vitro lymphocyte proliferative response in patients with ulcerative colitis and in health persons. We found that patients with ulcerative colitis show enhanced reactivity to PHA, when incubated in the presence of beta-endorphin. The activity of the disease during the period of the investigation seemed to play no role, since lymphocytes from both patients in exacerbation or remission reacted in a similar manner.