Acute appendicitis in the developing world is a morbid disease

IntroductionAcute appendicitis in the developing world has a markedly different disease profile to that in the developed world.MethodsA retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis.ResultsA total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%.Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was £2,060,972.ConclusionsAcute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system.     

Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

Follicular fluid levels of anti-Müllerian hormone,insulin-like growth factor 1 and leptin in women with fertility disorders

Anti-Müllerian hormone (AMH), insulin-like growth factor 1 (IGF1) and leptin are produced in the granulosa cells of follicles and play an important role in the growth and maturation of follicles. The aim of our study was to monitor AMH, IGF1 and leptin levels in a group of healthy women and compare them to a group of women with fertility disorders. The second aim was the evaluation of biomarker levels in relation to the identified cause of infertility. Totally, 146 females were enrolled into our study. Seventy-two healthy controls and seventy-four females with fertility disorders were divided into four subgroups: anovulation, endometriosis, fallopian tube damage, unknown reason. IGF1 was the only biomarker with significantly lower levels throughout the entire group with fertility disorders. We did not identify any statistically significant differences for AMH and leptin. Regarding subgroups, significant differences were only observed in the group of anovulatory women. AMH and leptin showed higher levels while IGF1 showed lower levels. In conclusion, levels of AMH, IGF1 and leptin found in follicular fluid are sensitive markers for anovulatory fertility disorders. AMH, IGF1 and leptin levels in follicular fluid have no relation to the fertility disorders caused by endometriosis, fallopian tube damage or disorders with unknown etiology.

Abbreviations: AMH: anti-Müllerian hormone; IGF1: insulin-like growth factor 1; PCOS: polycystic ovary syndrome     

Phase Composition of Al-Si Coating from the Initial State to the Hot-Stamped Condition

The chemical and phase composition of the coating and the coating/substrate interface of an Al-Si-coated 22MnB5 hot stamped steel was investigated by means of SEM-EDS, XRD, micro-XRD and electron diffraction. Moreover, the surface profile was analyzed by XPS and roughness measurements. The XPS measurements showed that the thickness of the Si and Al oxide layers increased from 14 to 76 nm after die-quenching, and that the surface roughness increased as well as a result of volume changes caused by phase transformations. In addition to the FeAl(Si) and Fe₂Al₅ phases and the interdiffusion layer forming complex structures in the coating, electron diffraction confirmed the presence of an Fe₂Al₅ phase, and also revealed very thin layers of Fe₃(Al,Si)C, Fe₂(Al,Si)₅ and Al-bearing rod-shaped particles in the immediate vicinity of the steel interface. Moreover, the scattered nonuniform layer of the Fe₂Al₈Si phase was identified in the outermost layer of the coating. Despite numerous studies devoted to researching the phase composition of the Al-Si coating applied to hot stamped steel, electron diffraction revealed very thin layers and particles on the coating/substrate interface and outermost layer, which have not been analyzed in detail.     

The protein product of the proto-oncogene c-cbl forms a complex with phosphatidylinositol 3-kinase p85 and CD19 in anti-IgM-stimulated human B-lymphoma cells

Multiple signal transduction cascades, consisting of multiple interacting proteins, are activated following stimulation through most cell surface receptors, including the immunoglobulin receptor of B lymphocytes. In this report, we investigated the multimolecular complexes formed following anti-Ig stimulation of a human B-lymphoma cell line, resulting in activation of phosphatidylinositol 3-kinase (PI3K). PI3K is a lipid kinase that consists of an 85-kD regulatory subunit, bound to a 110-kD catalytic subunit. CD19 is a 95-kD B-cell surface marker that contains a consensus binding motif for PI3Kp85 in the cytoplasmic domain and recruits PI3K activity in activated B cells. The protein product of the c-cbl protooncogene is a 120-kD protein that is expressed in early B-lineage cells and in myeloid cells and is phosphorylated on tyrosine following receptor-mediated signaling in T and B lymphocytes. We demonstrate here that phosphorylated c-cbl complexes with CD19 and with PI3Kp85 via its C-terminal SH2 domain, and that both c-cbl and CD19 are associated with active PI3K in anti-Ig- stimulated cells. Although we cannot differentiate between a three- component, c-cbl/CD19/p85 complex and individual two-component complexes, these studies suggest that c-cbl may function as a docking protein, possibly linking distinct signal transduction pathways.     

Protein-tyrosine kinase p72syk in Fc gamma RI receptor signaling

In this report we show that gamma-interferon (IFN) induces the expression of the nonreceptor protein tyrosine kinase, p72syk, and that cross-linking the Fc gamma RI receptor in IFN-differentiated U937 cells (U937IF cells) results in the activation of syk kinase. We show that syk is tyrosine phosphorylated (12-fold increase) after Fc gamma RI cross-linking. In vitro kinase assays demonstrate that the specific kinase activity of syk increased eightfold after Fc gamma RI cross- linking. The activation of signal transduction through the Fc gamma RI receptor, as measured by the respiratory burst, is associated with the tyrosine phosphorylation and catalytic activation of the syk kinase. We show that syk coprecipitates with the gamma subunit of the Fc gamma RI, Fc gamma RI gamma. The data suggest that p72syk is involved in signal transduction through the Fc gamma RI receptor, involving the Fc gamma RI gamma subunit.     

Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.     

Active immunization of murine allogeneic bone marrow transplant donors with B-cell tumor-derived idiotype: a strategy for enhancing the specific antitumor effect of marrow grafts

Persistence of the underlying malignancy remains the major obstacle limiting the success of high-dose chemoradiotherapy with allogeneic bone marrow transplantation (BMT) for lymphomas and multiple myeloma. We used the C3H 38C13 murine B-cell lymphoma, which expresses and secretes clonally derived Ig, the idiotype of which can serve as a tumor-specific antigen, to test the principle of transfer of tumor idiotype-specific immunity with BM. BALB/c marrow donors were twice immunized with 38C13-derived Ig, or with an isotype-matched control Ig, conjugated to keyhole limpet hemocyanin. Lethally irradiated C3H recipients reconstituted with marrow from idiotype immune, but not nonspecifically immune, donors demonstrated protection against subsequent lethal tumor challenge. The immunoprotective effect of immune allogeneic marrow was abrogated by T-cell depletion of the marrow graft before infusion. Low levels of serum anti-idiotypic antibody remained unaltered in recipients of T-cell-depleted immune marrow, consistent with a primary role for T-cell immunity in the cellular mechanism of this phenomenon. A modest therapeutic effect of immune allogeneic marrow was observed against 10 day, 1 cm established subcutaneous tumors, but only in combination with a booster immunization of the recipient post-BMT. These results provide the rationale for a novel strategy for enhancing the specific antitumor effect of allogeneic marrow grafts.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.