Book reviews and books received

Practices of Freedom: Selected writings on HTV/AIDS Simon Watney London, Rivers Oram Press, 1994 328 pp., £11.95 (paperback): £30 (hardback)

AIDS: The Challenge—Understanding Education and Care N. Small Aldershot, Avebury, 1993 172 pp.

Sex, Gay Men and AIDS P. M. Davies, F. C. I. Hickson, P. Weatherburn & A. J. Hunt London, Falmer Press, 1993 199 pp., £12.95

AIDS: Working with young people Peter Aggleton, Kim Rivers & Ian Warwick Horsham, West Sussex, Avert, 1993 162 pp., £ 18.95 (paperback)

ABC of AIDS. Third Edition Michael W. Adler (Ed.)London, BMJ Publishing Group, 1993 86 pp., £ 12.95 (paperback)

Guidelines for Management of Children with HTV Infection Diana Gibb & Sam Walters Horsham, West Sussex, AVERT, 1993 29 pp., £ 4 (paperback)

A Guide to HIV Infection and Child-bearing Danielle Mercey, Susan Bewley & Peter Brocklehurst Horsham, West Sussex, AVERT, 1993 25 pp., £ 3 (paperback)

Essential AIDS Information Resources AHRTAG/WHO, 1994 £ 5.00/US $10.00(Free to readers in developing countries)     

Book Review

Acquainted with the Night Allegra Taylor, 1989 London, Fontana £3.99 (paperback)

The AIDS Handbook Carl Miller 1990 Penguin Books 159pp. £4.99 (paperback)

Caring for Someone with AIDS Edited by David Yelding, 1990 Published for the Research Institute for Consumers Affairs by the Consumers Association and Hodder & Stoughton £6.95 (paperback)

AIDS. A Pocket Book of Diagnosis and Management Edited by A. Mindel, 1990 London, Arnold 244 pp. £12.95

AIDS and its Metaphors Susan Sontag, 1989 Harmondsworth, Penguin 98 pp. £3.99 (paperback)     

Selective apoptosis of multiple myeloma cells in primary samples induced by arsenic trioxide

Objectives

Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide (ATO) shows promising results in vitro, data from treatment of patients with MM are disappointing. Due to these discrepancies, we compared the efficacy and selectivity of ATO at two different concentrations in samples from MM patients.

Methods

The extent of apoptosis induced by 2 and 5 µM ATO was evaluated by flow cytometry using annexin V. 34 diagnostic bone marrow samples obtained from MM patients were analysed.

Results

5 µM ATO efficiently induced apoptosis in primary samples. Besides efficacy, also selectivity of action on MM cells in comparison to remaining haematopoietic cells was demonstrated for 5 µM ATO but not for 2 µM ATO.

Discussion

Our study on primary samples confirmed that ATO has a potential role in therapeutic management of MM. Further controlled studies on MM patients are needed.     

Acute physiological responses to physiotherapy applications pre and post autologous stem cell transplantation: an experimental study

Objective

We aimed to investigate the acute physiological responses (APR) to physiotherapy applications in patients undergoing autologous stem cell transplantation (ASCT), the difference between pre- and post-ASCT according to APR.

Methods

Twenty-six patients who were hospitalized for ASCT attended regular physiotherapy program. APR was recorded in the beginning and at the end of each exercise session. The differences in APR were calculated for each session. The mean values of the differences in APR were computed in pre-conditioning, pre-, and post-ASCT. Daily complete blood counts were also recorded during ASCT.

Results

Hemoglobin and platelet counts were significantly lower pre- and post-ASCT. Neutrophil counts were significantly lower post-ASCT. The difference in systolic blood pressure (SBP) in the beginning and at the end of the exercise sessions was significantly higher post-ASCT in comparison to pre-ASCT.

Conclusion

There was no significant change in APR except the SBP which suggests that similar level of exercise intensity could be tolerated in pre- and post-ASCT periods as well as preconditioning.     

Nucleostemin knocking-down causes cell cycle arrest and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells via p53 and p21Waf1/Cip1 up-regulation

Objectives

Nucleostemin (NS), a recently discovered nucleolar protein, is essential for maintaining self-renewal and proliferation of embryonic and adult stem cells as well as cancerous cells. The aim of this study was to determine biological function of NS in MOLT-4 cells as a human T-cell acute lymphocytic leukemia (T-ALL) model.

Methods

Efficacy of a specific small interference RNA on NS depletion was studied by quantitative polymerase chain reaction and western blotting. The growth rate and viability were analyzed by trypan blue exclusion test. Fluorescent microscopy was used for detecting apoptosis. Cell cycle and apoptosis were mechanistically studied by flow cytometry and western blotting.

Results

Knockdown of NS inhibited proliferation, arrested the cell cycle, and induced apoptosis through p53 and p21^Waf1/Cip1 pathways in MOLT-4 cells.

Discussion

These findings demonstrate critical roles of NS in MOLT-4 cells and may implicate on its therapeutic potential in this human T-ALL model.     

Influence of age on the correlations of hematological and biochemical variables with the stability of erythrocyte membrane in relation to sodium dodecyl sulfate

Objectives

To evaluate the influence of age on the relationships between biochemical and hematological variables and stability of erythrocyte membrane in relation to the sodium dodecyl sulfate (SDS) in population of 105 female volunteers between 20 and 90 years.

Methods

The stability of RBC membrane was determined by non-linear regression of the dependency of the absorbance of hemoglobin released as a function of SDS concentration, represented by the half-transition point of the curve (D₅₀) and the variation in the concentration of the detergent to promote lysis (dD).

Results

There was an age-dependent increase in the membrane stability in relation to SDS. Analyses by multiple linear regression showed that this stability increase is significantly related to the hematological variable red cell distribution width (RDW) and the biochemical variables blood albumin and cholesterol.

Discussion

The positive association between erythrocyte stability and RDW may reflect one possible mechanism involved in the clinical meaning of this hematological index.     

Bleeding manifestations apparently unrelated to coagulation or other organic disorders: A tentative classification and diagnostic clues

Objective

To study the features of bleeding conditions apparently not associated with vascular, platelet, or clotting dysfunctions.

Method

Conditions that may meet these criteria are: Münchausen syndrome factitious or fictitious, suicidal or homicidal bleeding, bleeding due to self-punishment, stigmatization, the battered child syndrome, and psychogenic bleeding.

Results

The importance of these variegate conditions is not trivial in clinical practice. Differential diagnosis may be difficult and involve other specialists besides hematologists. Occasionally, invasive procedures are involved.

Discussion

The occurrence of bleeding in patients, without a clotting defect or a systemic disorder and a negative family history for bleeding represents a diagnostic challenge. A careful examination of the physical and psychological status of the patient and an appropriate evaluation of the environment in which bleeding occurs, is always needed.     

A killer revealed: 10-year experience with beta-thalassemia intermedia

Objectives

Patients with beta-thalassemia intermedia tend to present later in life with milder anemia than beta-thalassemia major patients. The incidence of mortality and its causes in this patient population remains unknown. We aim to reveal the incidence and most common causes of death in this population.

Methods and results

We reviewed the charts of all of the beta-thalassemia intermedia patients who had been followed at the Chronic Care Center in Hazmieh, Lebanon during a 10-year period. A total of 18 patients out of 127 had died during the follow-up period giving a cumulative 10-year mortality incidence of 14%. The most common causes of cardiac deaths were due to renal and cardiac causes.

Discussion

Most causes of death have been linked to the high levels of iron coupled with anemia present in this patient population. Many of deaths could be prevented by adequate treatment.

Conclusion

Larger studies with more comprehensive data capture on risk factors of mortality in this patient population are called for.     

Incidence of internal tandem duplications and D835 mutations of FLT3 gene in chronic myeloid leukemia patients from Southern India

Objective

To screen two important FLT3 mutations (internal tandem duplication (ITD) and D835 point mutations) in chronic myeloid leukemia (CML) patients from Southern India and report their incidence.

Methods

Screened 350 CML patients and 350 controls for the two FLT3/mutations through polymerase chain reaction and restriction fragment length polymorphism methods.

Results

ITDs were detected in 12 of the 350 CML patients (3.4%) and D835 mutations in only four cases (1.14%), relatively low in frequency as compared to those reported earlier from non-Indian populations. None of the cases showed simultaneous occurence of both ITD and D835 mutations.

Discussion

These FLT3 mutations seem to be very rare in CML, and it is possible that these could be found only in a subset of patients who are in the progressive stage and/or with varied drug response. Prospective studies are needed to confirm the role of FLT3 mutations in CML pathogenesis, which may help devising therapeutic interventions.     

Heterogeneity in clinical course of EBV-associated lymphoproliferative disorder after allogeneic stem cell transplantation

Objective and Importance

Post-transplant lymphoproliferative disorder (PTLD) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associated with Epstein–Barr virus (EBV).

Clinical presentations

Among 263 individuals treated with allo-HSCT for severe aplastic anemia, pure white cell aplasia, T-prolymphocytic leukemia, and relapsed Hodgkin lymphoma, we diagnosed EBV-PTLD in 5 patients. Median age was 29 years (range 19–70 years) and four of five patients were EBV-seropositive prior to HSCT. All five had unrelated EBV-positive donors. In all cases, PTLD occurred within the first year post-transplant (median 4 months).

Intervention

There were two rapidly fatal courses with extensive organ involvement. Both patients showed lymphopenia and thrombocytopenia. In contrast, the three surviving patients had higher lymphocytes and normal platelet counts, while PTLD was restricted to one site and resolved after 2–4 cycles of rituximab.

Conclusion

In this case series courses of PTLD showed substantial diversity.     

Hb Koln [β98(FG5) [GTG → ATG,Val → Met]: The first report from India

Background

The group of unstable hemoglobins are associated with congenital non-spherocytic hemolytic anemia due to instability of the hemoglobin molecule. They often lead to formation of the characteristic inclusion bodies or Heinz bodies.

Aim

To identity the cause of mild anemia, reticulocytosis, and hepatosplenomegly in a case of non-spherocytic hemolytic anemia.

Materials and methods

A 34-year-old female patient originating from Maharashtra, western India presented with mild anemia and jaundice which had persisted since childhood. Investigations included a complete blood count, screening for red cell membrane protein defects, Hb analysis by high-performance liquid chromatography (HPLC) and cellulose acetate electrophoresis (pH 8.9), heat instability test and DNA sequencing.

Results

Hemoglobin analysis by HPLC showed an abnormal peak in the Hb C window (9.8%) with a retention time of 4.90 minutes. Cellulose acetate electrophoresis (pH 8.9) showed a slow moving band (6.15%) between Hb A₂ and Hb S. The heat instability test was positive. DNA analysis of α globin genes showed absence of both deletional and non- deletional α thalassemia. DNA sequencing of the β globin gene revealed heterozygosity for a mutation at codon 98 [GTG → ATG, Val → Met], which gives rise to Hb-Koln.

Conclusion

Hb Koln is the commonest unstable Hb variant reported from many populations in the world. However, this is the first report of this unstable Hb variant from India.     

BCR-ABL inhibitors: Updates in the management of patients with chronic-phase chronic myeloid leukemia

Objectives

This article reviews recent clinical experiences with first-line and second-line second-generation BCR-ABL inhibitors and discusses considerations for selection of therapy for patients with chronic-phase chronic myeloid leukemia.

Methods

We reviewed recent publications on PubMed and abstracts from major congresses relevant to the topic.

Results

Therapeutic options for front-line treatment have increased with the approval of two second-generation BCR-ABL inhibitors, dasatinib and nilotinib. Both agents are also treatment options for patients with resistance or intolerance to front-line imatinib. More recently, bosutinib, ponatinib, and omacetaxine have also been approved for patients with resistance or intolerance to prior therapy.

Discussion

Expanded treatment options coupled with rapidly changing treatment guidelines have led to numerous questions regarding the selection and monitoring of therapy. Common concerns include how to best select therapy based upon patient-specific comorbidities, monitoring and interpretation of treatment outcomes, and optimization of dosing when side effects occur.     

Angiogenesis and acute myeloid leukemia

Background

Angiogenesis is a word of Greek origin, ‘angeio’ refers to blood vessel, and genesis refers to creation, meaning the generation of new blood vessels. This process is essential for vertebrate development and plays a key role in human diseases. Angiogenesis is generally understood to be essential for the growth and metastasis of solid tumors and is also important in acute myeloid leukemia (AML).

Methods

This review summarizes the essential features of physiological and tumoral angiogenesis and the methods used for their assessment.

Results

Technologies for evaluating angiogenesis in AML are discussed and the prognostic significance of angiogenic factors is considered in the context of optimizing treatment.

Conclusion

As acute myelogenous leukemia and endothelial cells depend on each other for survival and proliferation, therapy directed against several pro-angiogenic factors might help to enhance the AML outcome.     

Book Reviews

AIDS—Action Now Helen Jackson, 1989 Zimbabwe, AIDS Counselling Trust (Harare) Z$5 (£1.60)

AIDS—Home Care and Hospice Manual AIDS Home Care & Hospice Program San Francisco [first published in 1987]

AIDS and AIDS-Related Infections: current strategies for prevention and therapy Adrian J. Bint, John Oxford & Phillip J. Daly, 1989 London, Academic Press £12.50 (paperback)     

Elevated levels of T-cell immune response cDNA 7 in patients with immune thrombocytopenia

Objectives

This study aimed to investigate the expression levels of T-cell immune response cDNA 7 (TIRC7) in immune thrombocytopenia (ITP) patients before and after high-dose dexamethasone (HD-DXM) treatment.

Methods

Forty-four patients with ITP were enrolled and received dexamethasone (40 mg/day) for 4 consecutive days. Patients who had platelet counts more than 50 × 10⁹/l or less were defined as responders or non-responders, respectively. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to measure RNA level and plasma level of TIRC7, respectively.

Results

TIRC7 levels (RNA and plasma level) were significantly higher in ITP than that in control (P < 0.0001). However, after treatment, TIRC7 levels were significantly decreased in responders (P < 0.0001) but not in non-responders (P > 0.05).

Discussions

TIRC7 might be associated with the pathogenesis of ITP, and TIRC7 levels could be used as an indicator to evaluate patients’ response to HD-DXM treatment.     

Risky behaviours of Jamaican adolescents with sickle cell disease

Objectives

To describe the risky behaviours of Jamaican teens with sickle cell disease (SCD) and compare them to a national sample of Jamaican youth.

Methods

One hundred twenty two SCD adolescents, 15–19 years old, completed the standardized questionnaire used in the Jamaican Youth Risk and Resiliency Behaviour Survey (JYRRBS), which was a nationally representative survey of 1317 Jamaican youths. Information was obtained on socio-demographics, smoking, alcohol use, and sexual activity. Secondary data from the JYRRBS were extracted to measure the difference in risky behaviours between the groups.

Results

Almost 50% of SCD and 58% of national teens reported having had sexual intercourse. More SCD teens used alcohol (77.7% vs. 60.7%; P value = 0.001). Risky behaviours tended to coexist and living with a parent (odds ratio: 0.62, P value <0.01) and currently attending school (odds ratio: 0.43, P value <0.001) lowered the likelihood of having had sex.

Discussion

SCD teens engage in many risky behaviours and health care professionals should screen and counsel them at each visit.     

Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents,new spectrum of infections

Objective and importance

Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6–8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients.

Clinical presentation

We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib.

Intervention

The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients.

Conclusion

Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.     

Ribosomal protein S14 silencing inhibits growth of acute myeloid leukemia transformed from myelodysplastic syndromes via activating p53

Objectives

Ribosomal protein S14 (RPS14) plays a key role in erythropoiesis and causes p53 activation in 5q- syndrome. However, the oncogenic potential of RPS14 is not understood in leukemia and high-risk myelodysplastic syndrome (MDS). Here, we investigated the changes of proliferation and apoptosis of SKM-1, an acute myeloid leukemia (MDS/AML) cell line transformed from MDS, and explored the role of RPS14 in them.

Methods

SKM-1 cells were transfected with recombined lentiviral vector shRPS14. Reverse-transcribed polymerase chain reaction and western blot assay were carried to detect the expression of RPS14 and p53. Cell proliferation was determined by MTT assay. Cell cycle and apoptosis were detected through flow cytometry.

Results

When compared with negative control, the proliferation rate of SKM-1 cells transfected with RPS14 hairpin siRNA dropped by 30%. Transfected SKM-1 cells presented with activation of p53. Transfection also arrested cells in G₀/G₁ phase and induced apoptosis, indicating that RPS14 is involved in the pathophysiology of MDS/AML.

Discussion

These findings indicate that partial silencing of RPS14 inhibits the proliferation of MDS/AML cells, and RPS14 may negatively regulate p53 activation in MDS/AML cells.