Phase II trial of murine monoclonal antibody D612 combined with recombinant human monocyte colony-stimulating factor (rhM-CSF) in patients with metastatic gastrointestinal cancer

In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 ug/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim \u27). Monocyte surface marker analysis revealed a high baseline expression of CD Id \u27 cells in our patient popu lation with an additional increase with rhM-CSF therapy. We observed a correlation between the degree of thrombocytopenia and the pretreatment CD16+ monocyte count. Of the plasma cytokines assayed, serum Neopterin demonstrated the most consistent increase during rhM-CSF therapy. There was a significant difference in the half-life of the first and last dose of D612 (3S.8 ±2 versus 27 ±2.9 h; P \u3c 0.05). Eleven of fourteen patients developed low-moderate levels of anti-D612 antibody. Despite the ob served biological activity of both rhM-CSF and D612 and the previously described in vitro synergy, no clinical antitumor responses were observed in this Phase II study

A decade of Anti-Retroviral Therapy in Nigeria: Efficacy of First Line Regimens in Treatment-Naive HIV/AIDS Patients.

Background: The proportion of persons who become infected with resistant strains of HIV may be increasing. We assessed the efficacy of first line anti-retroviral (ARV) regimens since they were first introduced in Nigeria.Methods: A descriptive prospective cohort study comparing baseline body mass index (BMI), CD+4 counts th and viral load (VL) with those obtained at 6th month of highly active antiretroviral therapy (HAART) in 300 HIV infected treatment-naive patients. Data were analysed with Epi-Info version 3.3 software and a probability value < 0.05 was considered significant.Results: The mean BMI at baseline of 22.9±4.6 kg/m2 th increased to 24.6±4.4 kg/m2 at 6th month of HAART. Therefore, the absolute increase in mean BMI was 1.7kg/m2 and was statistically significant p<0.05. The median CD4+ counts at baseline and at the end of the study shows counts of 127 cells/μl and 236 cells/μl respectively. This corresponds to a median increase of 109 cells/μl but was not statistically significant p=>0.05. When immunological response was measured as an increase from baseline of at least 50cells/μl, the proportion of patients with CD4+ count increase = 50cells/μl at the sixth month of HAART was 68%. The baseline median viral load was log1o 4.90, log10 (IQR 3.41-6.41) but became less than log10 2.60, log10 (IQR 2.60-5.26) at 6th month of  HAART. Hence, a median viral load reduction of at least log10 2.30 p<0.05 was achieved.Conclusion: This study supports the belief that using limited ARV regimens can result in acceptable treatment outcomes many years after they were first introduced.Key Words: HIV, antiretroviral drugs, efficacy, Nigeri

Addressing the challenge of neonatal mortality.

Reducing neonatal mortality remains a challenge with an estimated 3.0 million neonatal deaths in 2011, three-quarters of these in sub-Saharan Africa and Southern Asia. The leading causes of neonatal death globally are complications of preterm birth, intrapartum-related causes and infections. While post-neonatal, under-5 deaths fell by 47% between 1990 and 2011, neonatal deaths only fell by 32% and they now account for 43% of all under-5 child deaths. This article reviews the progress in reducing neonatal deaths in high-burden countries and presents an overview of known effective interventions to reduce neonatal mortality and the challenges faced in implementing these in high-burden settings. Effective action is possible to reduce neonatal mortality, but innovative approaches to implementation will be required if these preventable deaths are to be avoided

Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up

AIM: To assess the evolution of duodenal lymphocytosis (DL), a condition characterized by increased intraepithelial lymphocytes (IELs), over 2 years of follow-up. METHODS: Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease (CD) were included. Evaluation of IELs infiltrate in duodenal biopsy samples was carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: IgG and IgA anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance imaging were performed when necessary. Risk factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR. RESULTS: Eighty-five patients (16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed IgG anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity (GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn's disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25 (OR = 1640.4) or 15-25 (OR = 16.95), human leukocyte antigen (HLA) DQ2/8 (OR = 140.85) or DQA1∗0501 (OR = 15.36), diarrhea (OR = 5.56) and weakness (OR = 11.57). GS was associated with IELs 15-25 (OR = 28.59), autoimmune thyroiditis (OR = 87.63), folate deficiency (OR = 48.53) and diarrhea (OR = 54.87). CONCLUSION: DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS

Evaluation of the effects of the anti-retroviral drug regimen (zidovudine + lamivudine + nevirapine) on CD4 count, body weight, and Hb% of the HIV patients-a retrospective study

Abstract The main objective of study is to evaluate the effectiveness of triple drug therapy Zidovudine + lamivudine + nevirapine on cd 4 counts, weight and Hb% for the duration of 6 months. In this retrospective study, data was collected from the anti-retroviral therapy (ART) centre where 315 subjects infected with HIV received ZIDOVUDINE + LAMIVUDINE + NEVIRAPINE. Baseline and after 6 months of therapy; CD4 count, weight and Hb% were recorded and compared. Records with incomplete data were excluded. Statistical analysis was done using paired 't' test for body weight , Hb% and CD4 count.It was found that after 6 months of treatment, both CD4 count and body weight improved significantly(p value: 0.001). Whereas in case of haemoglobin %, even after the treatment period, no significant changes were observed in Hb % (p value: 0.227).It was concluded that ZLN regimen for treatment in HIV patient is efficacious in improving both CD4 count and body weight and not Hb%