Granulocyte-macrophage colony-stimulating factor is an endogenous regulator of cell proliferation in juvenile chronic myelogenous leukemia

Juvenile chronic myelogenous leukemia (JCML) is a rare myeloproliferative disorder of early childhood that is clinically and cytogenically distinct from the well-recognized adult type of chronic myeloid leukemia. Unlike the adult disease, growth of hematopoietic progenitors from peripheral blood (PB) occurs in the absence of exogenous stimulus even at low cell densities. This so-called "spontaneous" growth can be abrogated by adherent cell depletion and appears to depend on production of endogenous growth factors. We studied seven children with JCML to determine the nature of endogenous stimulators. With isolated PB mononuclear cells (PBMNCs) and a 3H- thymidine (3H-TdR) incorporation assay, JCML cells were shown to incorporate high levels of 3H-TdR when cultured in the absence of stimulus even at low cell densities. When neutralizing antisera prepared against each of the four known colony-stimulating factors (CSFs), GM-CSF, G-CSF, M-CSF, and interleukin-3 (IL-3), as well as antisera against interleukin-1 (alpha and beta) and tumor necrosis factor (TNF) were added to these cultures, only the antisera against recombinant human GM-CSF (rhGM-CSF) consistently resulted in significant inhibition of cell proliferation, achieving up to 72% inhibition of 3H-TdR incorporation in one case. Monoclonal antibodies (MoAbs) against rhGM-CSF resulted in a similar and highly significant degree of inhibition. A marked inhibitory effect of rhGM-CSF antiserum on "spontaneous" growth of PB CFU-GM derived colonies in semisolid medium was also demonstrated in four of five patients studied (87% to 90% inhibition). Production of growth factors by highly enriched JCML monocytes was variable. When initially studied in five of the seven patients, the monocytes from three of the patients revealed increased release of IL-1-like activities; two patients had levels similar to those of controls. One patient with normal levels when initially studied was later shown to have markedly increased amounts of IL-1-like activities in a second preparation of monocyte-conditioned medium (MCM). High levels of GM-CSF were detected in the initial MCM from one patient, but this may have indirectly reflected elevated IL-1-like activities present in the MCM. IL-3 and M-CSF levels were either low or undetectable in the patients studied as compared with MCM prepared with normal adult monocytes. These results clearly implicate GM-CSF as the primary endogenous regulator of JCML cell proliferation in culture and suggest that this malignant myeloproliferative disease may in part result from paracrine stimulation of marrow progenitor cells by growth factors/cytokines secreted by the malignant monocytes.     

Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20

Murine monoclonal antibody 2B8 specifically recognizes the CD20 phosphoprotein expressed on the surface of normal B lymphocytes and B- cell lymphomas. The light- and heavy-chain variable regions of 2B8 were cloned, after amplification by the polymerase chain reaction, into a cDNA expression vector that contained human IgG1 heavy chain and human kappa-light chain constant regions. High-level expression of chimeric- 2B8 antibody (C2B8) was obtained in Chinese hamster ovary cells. Purified C2B8 exhibited antigen binding affinity and human-tissue reactivity similar to the native murine antibody. In vitro studies showed the ability of C2B8 to bind human C1q, mediate complement- dependent cell lysis of human B-lymphoid cell lines, and lyse human target cells through antibody-dependent cellular cytotoxicity. Infusion of macaque cynomolgus monkeys with doses ranging from 1.6 mg/kg to 6.4 mg/kg resulted in greater than 98% depletion of peripheral blood (PB) B cells and 40% to 70% depletion of lymph node B cells. Recovery of PB B cells usually started at 2 weeks after treatment and required 60 to greater than 90 days to reach normal levels. As much as 95% depletion of B cells in peripheral lymph nodes and bone marrow was observed following weekly injections of 16.8 mg/kg antibody. No toxicity was observed in any of the animals. These results offer the possibility of using an "immunologically active" chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell lymphoma.     

Seropositivity of Chlamydophila pneumoniae immunoglobulin G antibody of HIV/AIDS patients in Abuja,Nigeria

ObjectiveTo detect IgG antibody to Chlamydophila pneumoniae (CP) in sera of HIV/AIDS patients and provide rationale for inclusion of routine screening for anti-CP antibodies and anti-chlamydial agents in the Nigerian National HIV/AIDS Management Plan.MethodsSerum samples from 34 consenting HIV/AIDS patients attended a Government-approved Antiretroviral Treatment Facility in Abuja were screened by enzyme-linked immunosorbent assay for anti-CP IgG antibody using ImmunoComb® Chlamydia Bivalent IgG Test kit (Orgenics, Israel).ResultsAnti-CP IgG antibody was detected in 20 (58.8%) of 34 patients tested. The detection rate was higher among the males (8/13; 61.5%) than the females (12/21; 57.1%). Patients of the age group 16-30 years had the highest (7/10; 70%) detection of anti-CP IgG antibody.ConclusionsThe result of the present study suggests the presence of anti-CP antibodies in sera of the HIV/AIDS patients, and reinforces the need for routine screening for anti-CP antibodies as a necessary intervention to reduce the burden of Chlamydophila pneumoniae (C. pneumoniae) infections and to reduce HIV-positive morbidity in Nigeria. The outcome of this study also provides justification for the possible inclusion of anti-chlamydial agents in the National HIV/AIDS Management Plan to provide prophylaxis against or treat active C. pneumoniae infections.     

Profile of Live-born Infants of In-vitro Fertilisation

Introduction

The Army Hospital (R&R) is the only service hospital providing in-vitro fertilisation (IVF) facility. Neonatal characteristics of live-born infants at this centre over a two-year period are analyzed in this study.

Methods

Data on 504 consecutive live-born IVF infants over a two-year period (01 Feb 2007 to 31 Jan 2009) were analysed.

Result

Of the 504 neonates, 190 (37.7%) were born by vaginal delivery, 156 (30.9%) by elective lower segment cesarean section (LSCS) and 127 (25.19%) following emergency LSCS. Maternal illness posing specific risk to the neonate was present in 165 out of 504 (32.7%). There were 239 (47.4%) preterm neonates. Males formed 51.8% of the cohort. Singletons accounted for 51.2%, while the rest (48.8%) were products of twin pregnancies. Small for gestational age neonates formed 22.6% (n = 114). A total of 20 (3.9%) infants had congenital malformations. There were 242 (48.1%) low birth weight neonates. A total of 128 (25.4%) neonates needed neonatal intensive care. Of the 504, there were 474 (94.1%) survivors while 30 (5.9%) did not survive. Twenty-nine (6.1%) neonates required readmission during the neonatal period.

Conclusion

In our setting, neonates born following IVF appeared to be at increased risk of prematurity, multiple births and low birth weight. Proper obstetric and neonatal management can result in good neonatal outcomes.Key Words: In-vitro fertilisation, Live-births, Low birth weight     

Pompe's disease in childhood: A metabolic myopathy

Background: Myopathy of metabolic origin in childhood occurs due to a variety of conditions. Pompe's Disease also known as Glycogen storage disease Type II, is a rare storage disorder with clinical presentation akin to spinal muscular atrophy.     

Children and adolescents with follicular lymphoma have an excellent prognosis with either limited chemotherapy or with a “watch and wait” strategy after complete resection

Data on clinical features and outcome in pediatric follicular lymphoma (pFL) are scarce. The aim of this retrospective study including 13 EICNHL and/or i-BFM study group members was to assess clinical characteristics and course in a series of 63 pFL patients. pFL was found to be associated with male gender (3:1), older age (72 % ≥10 years old), low serum LDH levels (<500 U/l in 75 %), grade 3 histology (in 88 %), and limited disease (87 % stage I/II disease), mostly involving the peripheral lymph nodes. Forty-four out of sixty-three patients received any polychemotherapy and 1/63 rituximab only, while 17/63 underwent a “watch and wait” strategy. Of 36 stage I patients, 30 had complete resections. Only one patient relapsed; 2-year event-free survival and overall survival were 94?±?5 and 100 %, respectively, after a median follow-up of 2.2 years. Conclusively, treatment outcome in pFL seems to be excellent with risk-adapted chemotherapy or after complete resection and an observational strategy only.     

Minimally invasive cardiac surgery using a flexible aortic clamp

Minimally invasive surgery for mitral valve disease has been performed using a variety of technologies, some of which are complex, have a steep learning curve, and are expensive. We have adopted a simple cost-effective approach over the last 7 years to perform a variety of minimally invasive procedures with excellent outcomes. There have been no strokes, no mortalities, and no episodes of limb ischemia in our series. No patient has required reoperation.     

The effect of postoperative immobilization on short-segment fixation without bone grafting for unstable fractures of thoracolumbar spine

Background:

Controversy regarding the fixation level for the management of unstable thoracolumbar spine fractures exists. Often poor results are reported with short-segment fixation. The present study is undertaken to compare the effect of fixation level and variable duration of postoperative immobilization on the outcome of unstable thoracolumbar burst fractures treated by posterior stabilization without bone grafting.

Patients and Methods:

A randomized, prospective, and consecutive series was conducted at a tertiary level medical center. Thirty-six neurologically intact (Frankel type E) thoracolumbar burst fracture patients admitted at our institute between February 2003 and December 2005 were randomly divided into three groups. Group I (n = 15) and II (n = 11) patients were treated by short-segment fixation, while Group III (n = 10) patients were treated by long-segment fixation. In Group I ambulation was delayed to 10th-14th postoperative day, while group II and III patients were mobilized on third postoperative day. Anterior body height loss (ABHL) percentage and increase in kyphosis as measured by Cobb''s angle were calculated preoperatively, postoperatively, and at follow-up. Denis Pain Scale and Work Scales were obtained during follow-up.

Results:

Mean follow-up was 13.7 months (range 3-27 months). At the final follow-up the mean ABHL was 4.73% in group I compared with 16.2% in group II and 6.20% in group III. The mean Cobb''s angle loss was 1.8° in group I compared with 5.91° in group II and 2.3° in group III. The ABHL difference between groups I and II was significant (P = 0.0002), while between groups I and III was not significant (P = 0.49).

Conclusion:

The short-segment fixation with amenable delayed ambulation is a valid option for the management of thoracolumbar burst fractures, as radiological results are comparable to that of long-segment fixation with the advantage of preserving maximum number of motion segments.