The effects of atrial fibrillation on functional recovery in post-stroke patients

Purpose : This study evaluates the negative effects of atrial fibrillation (AF) on after stroke recovery and its relationship with age and other concomitant diseases. Method : One hundred and ninety-nine consecutive inpatients, after their first stroke, were enrolled and entered a rehabilitation program lasting 60 days. The mean interval since the stroke was 19 days. The disability, both at admission and at discharge, was assessed by Functional Independence Measure (FIM). Atrial fibrillation was diagnosed at admission on the basis of electrocardiographic recordings. Gender, age, blood pressure and blood sugar level were also taken into account. Results : Stroke patients suffering from AF, when compared to those lacking AF, have higher disability at admission as well as at discharge and had a lesser gain in functional recovery. No statistical difference of the AF occurrence was found between male and female patients. The negative correlation between age and functional gain was found only in AF patients. There was also a significant association between AF and hypertension, but not between AF and diabetes. At the beginning and at the end of the study, the median FIM scores of all the patients with AF were quite similar irrespective of manifesting hypertension, diabetes or neither of these two. Conclusions : The presence of AF has a negative prognostic value on post stroke outcome, particularly in the elderly patients. The pattern of recovery of stroke subjects having AF is not influenced by concomitant diseases like hypertension or diabetes.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.     

From recipe to research: introducing undergraduate students to the nature of science using a hybrid practical course centred on drug discovery for neglected diseases

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The role of neutrophils in the development and outcome of zygomycosis in haematological patients

Zygomycosis constitutes the third leading cause of invasive fungal infections following aspergillosis and candidosis. Patients with haematologic malignancies or haematopoietic stem cell transplantation are particularly susceptible to zygomycosis. Neutropenia represents the most important pathogenic mechanism influencing the onset and outcome of zygomycosis. Neutrophils cause a lesion of the fungal wall with subsequent destruction by macrophages. They also enhance the activity of antifungal drugs against Zygomycetes. Strategies that aim to increase neutrophil count and function, such as granulocyte colony stimulating factor and granulocyte transfusion, could play an important role in the management of this life-threatening infectious complication.     

Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie alpha2 130 Ala --> Pro and Hb Caserta alpha2 26 Ala --> Thr) in a single HBA2 gene

This study describes a new molecular condition in the alpha(2)-globin gene (HBA2) found in six unrelated families from Southern Italy (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G-->A (Hb Caserta) and HBA2 130 G-->C (Hb Sun Prairie). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an alpha-thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with alpha degrees delectional thalassemia.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.     

Simultaneous infection with multiple herpesviruses.

Active dual infection with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was observed in four otherwise healthy persons with mononucleosis syndromes. A secondary serologic response to EBV occurred in three patients as determined by the presence of antibodies to EBV-induced nuclear antigen (EBNA) early in the illness. All four patients lacked heterophil antibodies; in the one case tested, immunoglobulin M (IgM) antibodies specific for EBV viral capsid antigen (VCA) were absent as well. The Guillain-Barré syndrome occurred in one patient, who also had active infection with herpes simplex virus 1 (HSV-1). In a fifth patient, herpes zoster developed complicating heterophil-positive infectious mononucleosis due to primary infection with EBV.These five cases demonstrate that mononucleosis syndromes may occur in association with dual or multiple herpesvirus infections and that reactivation of EBV may be common during heterophil-negative mononucleosis. Reactivation of latent virus is most likely related to depressed cellular immunity due to a primary infection with another herpesvirus. An alternate hypothesis is that viral DNA polymerase induced by infection with one herpesvirus might simultaneously permit the productive replication of a second herpesvirus previously latent within the same cell. Thus, reactivation may result from molecular interactions between viruses at the cellular level.The possibility of multiple infections must be considered whenever determining the specific viral etiology of heterophil-negative mononucleosis.