Neglected bilateral posterior shoulder fracture dislocation in an uncontrolled seizure patient

Posterior dislocation of the shoulder is a rare injury that occurs secondary to trauma and seizures. Diagnosis is often missed and treatment is challenging. Neglected posterior dislocation is associated with Hill-Sachs lesion which leads to locking of dislocation. Correct diagnosis is achieved by history taking, a physical examination and appropriate imaging. In neglected shoulder dislocation with uncontrolled seizure and humeral head defects of up to 45% the McLaughlin procedure shows excellent results at follow-up

Cellular and molecular responses of Saudi chronic myeloid leukaemia patients to imatinib (sti-571): ten year experience

The cyto-genetic hallmark of chronic myeloid leukaemia [CML], the Philadelphia chromosome [Ph], is the first consistent chromosomal abnormality that has been associated to a certain cancer type. In CML, Philadelphia chromosome is present leading to resistance to cell death and rapid proliferation. The aim of this study is to evaluate the different responses, toxicity and survival of Saudi CML patients to imatinib mesylate. All newly diagnosed CML patients who were treated with imatinib were included in this study. We investigated haematological, and molecular and cytogenetic responses by CBC, FISH and RT-PCR respectively. Cell proliferation and apoptosis were assayed using AUC and TUNEL respectively. Of the 12 cases, 9 [75%] were males and 3 [25%] were female. Four [33%] of the cases were diagnosed incidentally and 8 cases [67%] presented mainly with fatigue [75%], fever [58%], and splenomegaly [83%]. Signs of bleeding and rashes were rare at presentation. The majority of patients had low risk [8, 67%], and 33% had intermediate risk; but none of them had high risk CML. At the last follow up, 11 [92%] were in remissions. One patient [8%] was in remission after 3 years, 4 [33%] were in remission after 6 years, one was in remission after 7 years and 5 [42%] were in remission after 10 years. Only one patient had incomplete major molecular response [MMR] to imatinib after 12 years. The majority of the patients [10, 83%] were in MMR after 6 years and 42% of them were in MMR after 10 years of therapy. Adverse effects of imatinib were not reported by the patients. Imatinib treatment resulted in the reduction of proliferation and induction of apoptosis of CML CFU-GM cells. Imatinib mesylate is capable of treating Philadelphia chromosome-positive CP-CML without any adverse effects.

NKH477 inhibits proliferation and induces apoptosis in a panel of cancer cell lines

The anti-proliferative effects of cAMP in cancer cells may be regulated by the adenylyl-cyclase-V isoform. As Colforsin Daropate [NKH477] is more selective for this isoform, we hypothesized that this water soluble compound may promise utility as an oral anti-tumour agent. Using separate cancer cell lines [MCF7, HT29, A431, WiDr, RKO, A375, H630, Du145, SW480 and SW620], we studied the effects of NKH477 on cell proliferation, cell viability and apoptosis. NKH477 induced >70% inhibition of proliferation in all cancer cell lines tested. NKH477 induced a dose-dependent apoptosis causing G1 arrest and priming cells to die. NKH477 treatment on the tested cell lines inhibited proliferation and induced apoptosis. Thus, NKH477 shows early promise as an oral anti-cancer agent

Effect of nicotinamide on experimental induced diabetes

Insulin dependent diabetes mellitus [IDDM] results from irreversible loss of beta cells [Beta- cells] of the pancreas. A Streptozotocin [STZ]-induced diabetes in animal model mimics, in some aspects, recent onset IDDM. This study was conducted to investigate the effect of nicotinamide on experimentally-induced IDDM. Thirty Spraque Dawley rats were divided into 3 groups; a control group, a diabetic group which received an intraperitoneal [i.p.] injection of 55 mg/kg STZ and a nicotinamide group [1g/kg/day] which were dosed orally for 3 days followed by [i.p.] STZ [55 mg/kg] with the nicotinamide treatment continuing for an additional 14 days. Rats receiving STZ became diabetic after 2 weeks. This diabetic group showed hyperglycemia, and a very low level of C-peptide. Furthermore, pancreatic islets exhibited increased nitric oxide [NO] production together with an increased apoptotic index [as detected by TUNEL and electron microscopy]. Nicotinamide treatment prevented STZinduced diabetes, it also antagonized an increase in NO, and inhibited Beta-cell apoptosis. Fasting blood glucose, serum insulin and serum C-peptide were all within the normal range in the nicotinamide group. The nicotinamide protection of Beta-cells may be facilitated via inhibition of apoptosis and nitric oxide generation. It is suggested that nicotinamide might be considered an effective agent for the prevention and treatment of IDDM in prediabetic, and early stages, of IDDM

Programmed cell death of B lymphocytes is induced by ligation of integrin-associated protein [CD47]

As part of the Immunoglobulin [Ig] superfamily, the transmembrane glycoprotein CD47 forms a signalling complex with the CD23 receptor alphavbeta3 integrin, which stimulates cytokine synthesis and controls inflammation by regulating leukocyte activation and the phagocytosis of aging apoptotic leukocytes. To investigate the effects of anti-CD47 antibodies on a range of cell types at varying stages of development. Using flow cytometric analysis, KMS11 and H929 human B lymphocyte multiple myeloma cell lines were used to study the expression of CD47 and alphavbeta3 integrin as a means to explore the factors relating to the induction and resistance to apoptosis. We found that both cell lines expressed high levels of CD47, with KMS11 cells expressing more than H929 cells. CD47 stimulated an increase in apoptosis in both KMS11 and H929 cells with the preponderance being late apoptotic, dying cells. Ligation of CD47 via the soluble phase was crucial for apoptosis to take place. These results provided an insight into the apoptotic mechanisms involved in the control of inflammation surrounding the activation and phagocytosis of leukocytes. In conclusion, further analysis is required to elucidate the complete signaling cascade responsible for this proliferative effect. Induction of apoptosis via CD47 stimulation appears to occur in the absence of CD47's signaling complex partner, alphavbeta3 whether or not apoptosis occurs, appears to be dependent upon the cell type and also the way CD47 is engaged

Detection of IgG anti-beta2 glycoprotein-I antibodies in Saudi patients with systemic lupus erythematosis

To develop an assay for the measurement of this anti-human beta2-glycoprotein I [a beta2-GPI] This study was conducted from September 2004 to December 2006. The patients attending the Rheumatology Clinic were chosen from several centers in the Eastern region of Saudi Arabia because they had complications. An enzyme-linked immunosorbent [ELISA] assay was optimized and developed to measure IgG a beta2-GPI antibody levels in humans. Fifty normal blood donors arid 50 systemic lupus erythrematosis [SLE] patients were selected for this experiment. Raised IgG a beta2-GPI antibody levels were found in 80% of SLE patients. Interestingly, raised IgG a beta2-GPI antibody levels were associated with the presence of venous thrombosis and thrombocytopenia. The real value of IgG a beta2-GPI as a predictor for the future clinical complications needs to be confirmed in prospective controlled studies investigating clinical complications in relationship to IgG a beta2-GPI and to other risk factors for thrombosis

Apoptosis and eosinophils. Regulation and clinical relevance

Apoptosis, or program cell death, is a process of fundamental biological importance, and eosinophil apoptosis is believed to be the primary mechanism for removing eosinophils from the lung followed by their recognition and phagocytosis by macrophages or resident bronchial epithelial cells. There is, therefore, an increased interest in the fundamental role of the signals and intracellular signaling molecules that initiate and control apoptosis in human eosinophils though much remains to be established. This article reviews briefly the cross talks between apoptosis and eosinophils and summarizes the recent developments in this field