Profile of cytokine production in mixed kidney lymphocyte culture

Abstract Kidney cells are an important source of immunoregulatory molecules that regulate cell-to-cell interactions, which is the key step in the generation of the immunoresponse to alloantigens. In this study we identified the cytokines that are produced by both lymphoid cells and kidney cells when coincubated in mixed kidney lymphocyte cultures (MKLC). The capacity of kidney cells to stimulate the proliferation of effector allogeneic lymphocytes was assayed by incubating irradiated kidney cells and lymphocyte. The cytokine secretion profile in MKLC was investigated by incubating monolayers of kidney cells with effector peripheral blood mononuclear cells (PBMC). The culture supernatants were harvested on days 1, 2, 3, 4, 5, 6, 7, and 8 and assayed for IL-1β, IL-2, IL-6, and TNF alpha using an ELISA. Kidney cells, in comparison to PBMC stimulator cells were poor stimulators of the allo-proliferation even when HLA expression was increased by IFN gamma treatment. Compared to lymphocyte or kidney cells incubated alone, MKLC induced a considerable stimulation of cytokine production. This increase in cytokine production was observed essentially for IL-2 and IL-6 (at day 3, a 10-fold increase in IL-2 and a 5-fold increase in IL-6). This study provided evidence that target kidney cells and effector lymphocyte interactions generate a number of cytokines such as IL-11, IL-2, IL-6, or TNF alpha. These cytokines are known to modulate alloproliferation and generation of cytotoxic J lymphocytes (CTL).     

Noonan syndrome associated with central giant cell granuloma

We report a case of Noonan syndrome associated with central giant cell granuloma. The patient was a 101/2-year-old boy with the chief complaint of proptosis of the right eye. He also had various malformations such as short stature, webbed neck, pectus excavatum, cubitus valgus, pulmonary valve stenosis and patent foramen ovale, a characteristic face appearance and cryptorchidism and so on. Chromosome analysis showed a 46, XY karyotype. A computed tomographic scan and magnetic resonance imaging showed a mass originated from the lateral wall of the right maxillary sinus. The patient underwent Caldwell-Luc operation. Histological examination of the mass showed the characteristics of central giant cell granuloma. This case report describes a patient with the features of the recently described Noonan-like/multiple giant cell lesion syndrome.     

Outcome of acute intussusception in a regional paediatric centre

It has been suggested recently that acute intussusception should only be managed in a specialised paediatric centre. The aim of this study is to assess the incidence and outcome of acute intussusception in a comprehensive paediatric unit in Waterford Regional Hospital. It is a retrospective medical records study over a ten year period from June 1990 to June 2000. Our results showed that we had 24 cases giving an incidence of 2.4 cases per year. Contrast enema was performed in 23(95%) cases, successfully reduced in 14(61%) cases, unsuccessfully reduced in 7(30%). Surgical intervention was necessary in 7(30%) cases. Three (12.5%) cases were transferred to a specialised paediatric surgical centre. There were no perforation or death. We conclude from this study that management of acute intussusception can be successfully undertaken in a regional paediatric centre. It requires adequate throughput of cases and close co-operation between paediatrician, radiologist, anaesthetist, surgeons and of course a dedicated paediatric nursing staff.     

Does center or surgeon volume influence adoption of minimally invasive versus open pancreatoduodenectomy? A systematic review and meta-regression

BackgroundThere has been increasing uptake of minimally invasive pancreatoduodenectomy during the past decade, but it remains a highly specialized procedure as benefits over open pancreatoduodenectomy remain contentious. This study aimed to evaluate current evidence on minimally invasive pancreatoduodenectomy versus open pancreatoduodenectomy in terms of impact of center volume on outcomes.MethodsA systematic review of articles on comparative cohort and registry studies on minimally invasive pancreatoduodenectomy versus open pancreatoduodenectomy published until 31st December 2019 were identified, and meta-analyses were performed. Primary endpoints were International Study Group on Pancreatic Fistula grade B/C postoperative pancreatic fistula and 30-day mortality.ResultsAfter screening 7,390 studies, 43 comparative cohort studies (8,755 patients) with moderate methodological quality and 3 original registry studies (43,735 patients) were included. For the cohort studies, the median annual hospital minimally invasive pancreatoduodenectomy volume was 10. No significant differences were found in grade B/C postoperative pancreatic fistula (odds ratio: 0.98, 95% confidence interval: 0.78–1.23) or 30-day mortality (odds ratio: 1.14, 95% confidence interval: 0.65–2.01) between minimally invasive pancreatoduodenectomy when compared with open. No publication biases were present and meta-regression identified no confounding for grade B/C postoperative pancreatic fistula, center volume or 30-day mortality. Minimally invasive pancreatoduodenectomy was only strongly associated with significantly lower rates of postoperative pulmonary complications and surgical site infection, shorter length of stay, and significantly higher rates of R0 margin resections.ConclusionMinimally invasive pancreatoduodenectomy remains noninferior to open pancreatoduodenectomy for grade B/C postoperative pancreatic fistula but is strongly associated with significantly lower rates of postoperative pulmonary complications and surgical site infection. Minimally invasive pancreatoduodenectomy can be adopted safely with good outcomes irrespective of annual center resection volume.     

ASO Visual Abstract: The Landmark Series—Minimally Invasive Pancreatic Resection

Annals of Surgical Oncology -     

DNA minor-groove binders: results and design of new antitumor agents.

DNA minor-groove binding drugs have been extensively studied in the last years in order to influence the regulation of gene expression in neoplastic disorders by means of specific interactions with DNA bases. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs), CC-1065 and distamycins are three classes of minor-groove alkylating agents which showed interesting cytotoxicity profiles, but they cannot be used in humans for various toxicity problems. For this reason many groups applied heterocyclic substitutions extensively, in order to either modify the reactivity profile or introduce extra interactions within the minor groove, thus changing the binding site or modulating the binding sequence.     

Novel Mutations in the Amyloid Precursor Protein Gene within Moroccan Patients with Alzheimer's Disease

In Morocco, Alzheimer's disease (AD) affects almost 30,000 individuals, and this number could increase to 75,000 by 2020. To our knowledge, the genes predisposing individuals to AD and predicting disease incidence remain elusive. In this study, we aimed to evaluate the genetic contribution of mutations in the amyloid precursor protein (APP) gene exons 16 and 17 to familial and sporadic AD cases. Seventeen sporadic cases and eight family cases were seen at the memory clinic of the University of Casablanca Neurology Department. These patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging, and laboratory tests. Direct sequencing of exons 16 and 17 of the APP gene was performed on genomic DNA of AD patients. In this original Moroccan study, we identified seven novel frameshift mutations in exons 16 and 17 of the APP gene. Interestingly, only one novel splice mutation was detected in a family case. There is a strong correlation between clinical symptoms and genetic factors in Moroccan patients with a family history of AD. Therefore, mutations in APP gene exons 16 and 17 may eventually become genetic markers for AD predisposition.