Assessment of Apoptosis Regulating Factors BCL-2 and Fas Antigens on Malignant and Normal Plasma Cells

Multiple myeloma (MM) is characterised by slow proliferation of malignant plasma cells and their accumulation within the bone marrow. The dysregulation of programmed cell death (apoptosis) is a very important mechanism in the pathogenesis of this tumour. It prompted us to investigate the apoptosis regulating factors such as the pro-apoptotic Fas antigen and the anti-apoptotic protein BCL-2 on bone marrow malignant plasma cells in untreated patients with newly diagnosed MM and to compare them with their normal counterparts—plasma cells isolated from bone marrow of healthy individuals. Twenty-nine MM patients and 16 healthy persons were studied. Bone marrow mononuclear cells were isolated, indicated by monoclonal antibodies and analysed using the flow cytometry method. There was no statistically significant difference in BCL-2 expression in plasma cells between patients and control groups. However the percentage of BCL-2 positive cells was significantly related to the clinical stage of the disease. We detected statistically significant lower percentage of Fas positive cells in the patient group than in control.

We concluded that in MM at diagnosis the expression of BCL-2 in bone marrow malignant plasma cells was comparable to normal plasma cells but expression of Fas antigen on these cells was lower. It suggests that down regulation of Fas and normal regulation of BCL-2 may be implicated for myeloma cell survival and their escape from apoptosis in vivo.     

Non surgical treatment of subdural hematoma in a hemodialysis patient

The development of subdural hematoma in the course of hemodialysis treatment has been well documented in the literature. We report a case of a subdural hematoma in a patient on hemodialysis, in whom surgery was contraindicated, due to her concurrent use of anticoagulants. Good recovery was achieved by steroid treatment. Although surgical removal constitutes the essential therapeutic approach for subdural hematoma, we emphasize the importance of medical management in special cases where surgery is contraindicated.     

Long-term outcomes of primary ocular adnexal lymphoma treatment with intraorbital rituximab injections

Purpose

We recently reported on the efficacy of intralesional rituximab for treating primary ocular adnexal lymphoma in a pilot study. After treatment, a complete response was observed in two of five patients, a partial response in one patient, and lesion recurrence in two patients. In this study, we evaluate the long-term follow-up of the five previously treated patients as well as the response of two new patients to an augmented dose of rituximab.

Methods

We followed up the five patients who were treated with rituximab during the initial pilot study. Two additional patients were also enrolled and treated with four intraorbital injections of 10 mg rituximab once a week for 1 month (total dose of 40 mg). Median follow-up period was 4 years for the first five patients and 1 year for the last two patients.

Results

Lymphoma did not relapse in the two patients who originally responded immediately to treatment. Of the initial partial responders, one became disease-free after additional rituximab treatment, and one experienced a standardized uptake value reduction, as measured with positron emission tomography–CT. One patient who experienced abdominal and pulmonary localization 7 months later showed no local recurrence. The two newly enrolled patients had complete remission after the first cycle of treatment and no disease recurrence eight and 11 months later, respectively.

Conclusions

This study suggests that intralesional administration of rituximab for treating localized ocular adnexal CD20+ lymphomas could be an effective front-line therapeutic option with negligible side effects and a good response rate and duration.     

A biological window on psychological development

The articles in this special issue of Developmental Psychobiology were presented in May 2005 at an international institute on developmental science hosted by the University of North Carolina at Chapel Hill. Conducted annually at one of the participating universities, these meetings are intended to foster collaboration and build consensus on specific theoretical, methodological, and analytical issues faced by developmentally oriented researchers. The overall goal of the 2005 meeting, titled "Integrating Biology and Developmental Science," was to identify different ways by which a developmental study of psychological phenomena in their joint biological and behavioral aspects may shed new light on their organization in the individual. The six contributions to this special issue illustrate how a biological window on developmental processes can further this scientific endeavor.     

The influence of polymorphisms in the drug transporter,ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia

Background

Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL.

Epidural ketamine reduces post-operative epidural PCA consumption of fentanyl/bupivacaine

Purpose

To study the analgesic effect of epidural ketamine on postoperative pan and epidural PCA consumption after total abdominal hysterectomy.

Methods

Sixty-one ASA I–II patients, 34–60 yr were randomly assigned into three groups. Epidural catheters were inserted before induction of anaesthesia. Patients in group I and II received 30 mg ketamine epidurally before induction of anaesthesia or 20 min after skin incision: group III received placebo, Postoperatively, on first analgesia request, sedation score, Visual Analogue Scale (VAS), Prince Henry Score (PHS) and Bromage motor weakness score were taken and followed by an epidural bolus of 9 ml bupivacaine 0.25% + 50 μg fentanyl. Analgesia was maintained by PCA with a mixture of bupivacaine 0.1% + fentanyl 0.001% epidurally. Measurements were repeated at 1, 2, 4, 8, 12 and 24 hr.

Results

First analgesia request was 17 ±6.8 min in the control group compared with 31.4 ±23.8 and 44 ±23.1 min for groups I and II respectively. The differences between group III and group I (P < 0.05) and between group III and group II (P < 0,01) were statistically significant. Twenty four hour PCA consumption was 101.2 ±47.2, 87 ±27 and 162 ±38 ml for groups I, II and III respectively. The differences between group III and group I and that between group III and group II were statistically significant (P < 0.001 ).

Conclusion

Epidural ketamine 30 mg reduces post hysterectomy pain as evidenced by prolongation of time to first analgesia request and reduction in postoperative epidural PCA consumption. This effect is manifest whether ketamine is given before induction or 20 min after skin incision.     

Identification of novel genetic variations affecting osteoarthritis patients

Background

Osteoarthritis (OA) is a progressive joint disease characterized by gradual degradation of extracellular matrix (ECM) components in the cartilage and bone. The ECM of cartilage is a highly specified structure that is mainly composed of type II collagen and provides tensile strength to the tissue via aggrecan and proteoglycans. However, changes in the ECM composition and structure can lead to loss of collagen type II and network integrity. Several risk factors have been correlated with OA including age, genetic predisposition, hereditary factors, obesity, mechanical injuries, and joint trauma. Certain genetic association studies have identified several genes associated with OA using genome-wide association studies (GWASs).

Results

We identified several novel genetic variants affecting genes that function in several candidate causative pathways including immune responses, inflammatory and cartilage degradation such as SELP, SPN, and COL6A6.

Conclusions

The approach of whole-exome sequencing can be a promising method to identify genetic mutations that can influence the OA disease.