Intravenous gold-induced autologous serum injection therapy (Go ACT®) as a new treatment for seasonal pollen-based allergies.

OBJECTIVE: This prospective case study investigated the new therapeutic paradigm of autologous gold-induced immunotherapy (Go ACT®) in the treatment of pollen-based allergies. The safety and clinical efficacy of Go ACT® were investigated by assessing patients in the first pollen season following treatment with Go ACT®. PATIENTS AND METHODS: In this prospective case study, patients were enrolled who had a proven pollen allergy and had been previously unsuccessfully treated with standard medication. Clinical improvement following Go ACT® treatment was analyzed using symptom scores, ARIA classification and symptom control. The data generated in the case study were compared to the data from the previous pre-treatment pollen season. RESULTS: 16 patients were included in this study. The treatment was well tolerated by all patients. On completion of the study all of the patients rated the tolerability of the treatment as either good or very good. Local reactions to the treatment were not seen. No Serious Adverse Events (SAEs) occurred. The symptom scores decreased significantly from the 2016 pollen season to the 2017 pollen season in patients who received Go ACT® treatment. Analysis of the ARIA classification showed that 81.0% of patients had persistent, moderate-to-severe rhinitis before treatment.  Following treatment 7.1% of patients had persistent, moderate-to-severe rhinitis. A total of 62.4% of patients in the study achieved symptom control. A total of 38.8% of patients required no symptomatic medication after Go ACT® treatment. The rhino-conjunctivitis score was significantly lower after the treatment. CONCLUSIONS: This study has shown that Go ACT® treatment is safe, effective, well-tolerated and accepted by patients suffering from pollen allergy. The results of the symptom scores, RCAT, ARIA classification show that Go ACT® treatment elicits immediate beneficial effects during the pollen season under treatment and for the season following treatment.

Ophthalmology practice in Afghanistan during the COVID-19 pandemic.

This short communication described the actions taken in ophthalmic practice in Kabul, Afghanistan during the COVID-19 pandemic to effectively protect both patients and staff. By following World Health Organisation (WHO), international and local guidelines it has been possible to continue treating ophthalmic outpatients with minimum risk to both patients and staff. The changes which have been implemented may allow better overall infection control in the hospital which will continue to have benefits post-pandemic.

Dental pulp stem cells in regenerative medicine.

The mesenchymal stem cells (dental pulp stem cells; DPSC) found inside teeth represent a significant future source of stem cells for regenerative medicine procedures. This review describes the ontogeny of DPSC; the laboratory processing and collection of DPSC; the immuno-cytochemical characterisation of DPSC; the differentiation between adult DPSC and DPSC obtained from exfoliated deciduous teeth (SHED) and their potential use in regenerative medicine procedures in the future both in dental and general medical applications.

Cord blood: the future of regenerative medicine?

Cord blood stem cells have been in routine clinical practice for the past 20 years. The development of new therapeutic protocols in regenerative medicine require the use of stem cells and umbilical cord blood is an important and readily available source of cells for these applications. The latest concepts in routine transplantation of cord blood are reviewed followed by the critical role of cord blood stem cells in regenerative medicine research and novel approaches using cord blood as a source of whole blood for transfusion.

Will stem cells in cord blood, amniotic fluid, bone marrow and peripheral blood soon be unnecessary in transplantation?

There are now various sources of stem cells. Those derived from blastocysts, named embryo stem (ES) cells, have attracted most attention and are highly multipotent. Human cord blood became widely used as a source of stem cells with differing properties to ES cells and their therapeutic application has grown steadily as they are stored in increasing numbers of stem cell banks. Other sources of human stem cells are derived from peripheral blood and amniotic fluid. They may arise from a common origin in epiblast. This review stresses the use of cord blood stem cells, but describes new approaches which may supersede the use of most stem cells. The advantages and disadvantages of these various classes are described in relation to potential methods involving gene conversion to change somatic cells to ES cells.

The xenotransplantation of goat and human hematopoietic cells to sheep fetuses.

Hematopoietic xenografts were carried out in three experiments using goat fetal liver (44-48 days, experiments I and II) or purified human CD 34+ cells (experiment III) as the donor cells. Recipients were sheep fetuses at 41-47 days of gestation. Goat fetal liver cells were either injected without any pretreatment or stimulated by preincubation in a culturing in goat phytohemagglutinin-stimulated lymphocyte supernatant. Human CD 34+ myeloid progenitor cells were purified from bone marrow by minimacs immunomagnetic purification and cultured in medium supplemented with stem cell factor, IL3, and IL6. Goat-sheep chimerism was assessed by flow cytometry analysis (FCA) of peripheral blood and bone marrow cells using a mouse anti-goat CD 45 monoclonal antibody and by karyotype analysis of peripheral blood from goat/sheep chimeras. Human cell engraftment was assessed by polymerase chain reaction amplification of the human DAX1 gene in blood and bone marrow DNA from sheep which had received human cells. In the three experiments, a mean of 76% (26 of 34) of injected fetuses were born alive without any clinical evidence of graft-versus-host disease. Three lambs were found to be goat/sheep chimeric after flow cytometry analysis (peripheral blood and bone marrow) and karyotype (peripheral blood) analysis. Both tissues continued to express goat cells at 6 or 12 months (last assessment) depending on the experiment. No human chimerism was detected using polymerase chain reaction amplification in peripheral blood and bone marrow of any of the six sheep grafted with human cells. These data and those also obtained on other species (human, pig/sheep) show that it is possible to carry out hematopoietic xenografts using the sheep fetus as recipient provided both donor and recipient fetal cells are processed during the period of tolerance to foreign antigens.

Comparative stem cell biology.

This review collates data from a range of stem cells studies in an attempt to bring together an overall view of stem cell biology. Data from hemopoietic, keratopoietic, hepatopoietic and neuropoietic stem cells are presented. The developmental and cell biology of each system is discussed in an attempt to develop a comparative view of stem cell biology. Comparisons are drawn in the areas of clonal analysis, surface antigen expression, adhesion molecules and cytokine interactions. Where appropriate the role of embryonic stem (ES) cells is also considered in the developmental biology of the cells in question.

Embryonic stem cell grafting: the therapy of the future?

The grafting of mouse embryonic haemopoietic cells into deficient recipients is discussed. Donor cells can be obtained from post-implantation mouse embryos in vivo and used to treat X-irradiated or genetically anaemic recipients. The concept of grafting embryonic haemopoietic cells into normal, untreated recipients is also described. Preimplantation mouse blastocysts grown in vitro for 3-4 days can also be used as a source of donor cells. The haematological and immunological aspects of embryonic cell grafting are discussed, followed by a description of current xenotransplantation experiments, including rat into mouse and human into mouse. The review concludes with a discussion of the application of embryonic cell grafting to other tissues and a look into the possible future of this technique.

The use of Albuminar 5 as a medium supplement in clinical IVF.

Human serum and Albuminar 5 (A5) were compared as medium supplements to Earle's solution containing pyruvate in clinical IVF. One-hundred patients in each group showed a fertilization rate of 60% with serum and of 62% with A5. The overall pregnancy rates in the serum and A5 groups were 20 and 24%, respectively. The incidence of failed fertilization (6-7%) and of multipronucleate oocytes (4-5%) was similar in both groups. At 37 degrees C, sperm survived less well in A5 although the rate of fertilization was not reduced. Blastocyst formation was not seen in 'spare' embryos grown in vitro in medium containing 15% v/v A5.

Embryonic haemopoietic stem cell grafts in the treatment of murine genetic anaemia.

Embryonic haemopoietic stem cells obtained from early post-implantation mouse embryos can be successfully used in the treatment of murine genetic anaemia. Anaemic recipients had either chronic macrocytic anaemia, which was lethal without treatment, or mild anaemia without increased mortality. All successfully grafted recipients developed donor haemoglobin and glucose phosphate isomerase electrophoretic markers, indicating the presence of donor erythrocytes and lymphocytes. The minimum number of embryonic cells resulting in a successful graft in chronic macrocytic anaemia recipients was 0.8 x 10(6) nucleated cells. Athymic (nude) mice were also colonized by embryonic haemopoietic stem cells. Donor electrophoretic markers were seen but all recipients soon died, possibly of pneumonia. Bone marrow grafts into recipients with chronic macrocytic anaemia were not successful. Bone marrow grafts into recipients with mild anaemia resulted in some recipients showing donor markers. These recipients later died, showing symptoms of graft-versus-host disease.

Transplantation of embryonic haemopoietic stem cells without prior recipient X-irradiation.

Allogeneic day 7 mouse embryonic cells can colonize the haemopoietic system of normal, non-irradiated recipient mice. Donor embryonic cells are disaggregated and injected intravenously resulting in colonization in 40% of recipients, as shown by the presence of electrophoretic markers, characteristic of the donor cells. Donor type haemoglobin (Hb) and donor type glucose phosphate isomerase (GPI) demonstrates the presence of donor type erythrocytes and lymphocytes respectively. Repeat grafts in recipients not showing donor makers did not result in colonization. Recipient type haemopoiesis was dominant in all types of recipient. Skin grafts of allogenic donor type skin onto successfully grafted embryonic cell recipients did not survive. Allogeneic donor embryonic cells therefore survive in recipients where adult skin allografts do not. Donor embryonic cells, homozygous for T6 marker chromosomes, were used to assess the site of colonization of intravenously grafted cells. Donor chromosomes were seen in recipient liver and bone marrow at low levels. This distribution of donor cells persists for up to 64 d post-graft.

New advances in human embryology: implications of the preimplantation diagnosis of genetic disease.

The diagnosis of genetic disease in preimplantation embryos is discussed. The typing of spermatozoa may be feasible for factors such as the presence of an X and Y chromosome. Embryos might be typed by non-invasive methods, by assessing their uptake of metabolites although the widest opportunities may arise by the use of invasive methods which involve the removal of one or a small number of cells. The methods of diagnosis are discussed, including enzyme assays and the use of DNA probes, preliminary results with human embryos are presented and the difficulties related to these techniques are debated. The low rate of implantation of replaced embryos will mean that many embryos will have to be diagnosed, and certain embryological factors such as the high incidence of chromosomal imbalance and the problems of 'imprinting' might obscure certain diagnoses. The advantages and disadvantages of the method are discussed.

Differentiation of embryonic haemopoietic stem cells from mouse blastocysts grown in vitro.

Embryonic haemopoietic stem cells can differentiate from mouse blastocysts grown in vitro. Mouse blastocysts were cultured for 3 or 4 days and the resultant cells were injected intravenously into lethally X-irradiated or genetically anaemic recipient mice. Blastocysts grown in vitro did not maintain normal embryonic morphology. The presence of donor haemoglobin and donor lymphocytic glucose phosphate isomerase in grafted recipients, demonstrates the presence of embryonic haemopoietic stem cells. Recipients of embryonic haemopoietic stem cells, obtained from growth in vitro, were haematologically stable with no evidence of neoplasia. Pluripotent embryonic cells, maintained on fibroblast feeder layers, were unable to colonize X-irradiated or genetically anaemic mice. Recipients of pluripotent cells died at the same time as saline-injected controls.

Differentiation and grafting of haemopoietic stem cells from early postimplantation mouse embryos.

Haemopoietic stem cells evidently arise in early post-implantation mouse embryos at day 6 of gestation, a day earlier than previously thought (Moore & Metcalf, 1970). Disaggregated embryonic cells were injected into mice given a lethal dose of X-irradiation. The presence of donor haemoglobin (Whitney, 1978) and donor lymphocytic glucose phosphate isomerase (GPI) (Siciliano & Shaw, 1976) to detect donor erythrocytes and lymphocytes, respectively, were monitored by starch gel electrophoresis. The presence of donor cells was also assessed by using donor embryos carrying the T6 marker chromosomes. Decidual cells dissected free of embryos did not colonize any recipients. Disaggregated cells from early mouse embryos first colonized the liver and then repopulated the haemopoietic systems of recipients, producing adult donor haemoglobin within 2-3 days and donor GPI within 3-5 days. 80% of grafted X-irradiated recipients survived and donor markers were found in each of them. All nongrafted controls died within 14 days of X-irradiation and none of them showed donor markers. Disaggregated embryonic cells could be grafted across major histocompatibility barriers unlike adult bone marrow. Haemopoietic stem cells could not be identified in disaggregated cells from embryos aged less than 6 days gestation.