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Biomedical subjects

I Gerber

Publications and source records attributed to I Gerber.

13 recordsLinked to original sources

Stimulatory effects of creatine on metabolic activity, differentiation and mineralization of primary osteoblast-like cells in monolayer and micromass cell cultures.

The effects of creatine (Cr) supplementation on primary rat osteoblast-like cells cultured as monolayer and micromass were investigated. Cr was added to the medium at concentrations of either 10 or 20 mM. At various time points, the cell cultures were analyzed morphologically, metabolically and biochemically. The degree of differentiation of primary osteoblast-like cell cultures was higher in micromass cultures compared to monolayer cultures, as judged by alkaline phosphatase (ALP) activity and extent of mineralization. In both culture systems, Cr supplementation showed positive effects, which were dependent on the organizational level of the osteoblast-like cells in such a way that the cells in monolayer culture showed significantly increased metabolic activity, ALP activity and mineralization in the presence of Cr than without the supplement. In micromass cultures, Cr also significantly enhanced ALP activity and mineralization, without affecting metabolic activity. The effect of Cr on ALP activity was more pronounced at higher concentrations of Cr, but 20 mM Cr already showed some adverse effects on cell viability. In conclusion, chemically pure Cr added to low serum cell culture medium has a stimulatory effect on metabolic activity, differentiation and mineralization of osteoblast-like cells indicating that Cr supplementation could also be used as a potential clinical intervention to stimulate cell growth, differentiation and mineralization during bone repair in vivo.

Alkaline Phosphatase↗

[Therapeutic intensification and autologous stem cell transplantation in autoimmune diseases].

THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

Adolescent↗

Differentiation of rat osteoblast-like cells in monolayer and micromass cultures.

During intramembranous bone formation, preosteoblasts condense, differentiate into osteoblasts and deposit bone matrix. We compared the differentiation process of rat calvarial osteoblast-like cells inoculated as micromasses, which mimic the in vivo condensation process, with cells inoculated as monolayers. The cells were analysed morphologically at 1,2 and 3 weeks by light microscopy (alkaline phosphatase activity, mineralization), by transmission electron microscopy, and biochemically (collagen typing, alkaline phosphatase activity, protein and DNA content). The cells inoculated as monolayers formed alkaline phosphatase positive and mineralized nodules during the culture period. The cells inoculated as a micromass formed a large mineralized area consisting of smaller nodules. The ultrastructure of the cells in both culture systems showed the typical features of osteoblasts and osteocytes. The main difference between monolayer and micromass cultures was found after 1 week in culture. The cells inoculated as a micromass formed a multilayer of cells. The cytoplasm contained rER, mitochondria, vesicles and ribosomes. There were abundant collagen fibrils in membrane folds and in the extracellular matrix. This was in contrast to the cells in monolayer culture which showed hardly any collagen fibrils in the extracellular matrix. The promotion of the differentiation was also confirmed by biochemical data showing that the DNA content was lower in the micromass than in the monolayer cultures during the culture period. These results show that micromass, as compared to monolayer, culture promotes the differentiation of rat osteoblast-like cells in vitro.

Journal Article↗

Influence of cell isolation, cell culture density, and cell nutrition on differentiation of rat calvarial osteoblast-like cells in vitro.

The effects of various cell isolation procedures, growth media and the cell culture density on the in vitro differentiation of neonatal rat calvarial osteoblast-like cells were investigated. Cells were isolated by enzymatic treatment, or after explant culture and inoculated as a monolayer or micromass in serum containing BGJb, or Dulbecco's Modified Eagle Medium (DMEM). The cells were kept for up to 3 weeks in culture and were then characterized, both morphologically and biochemically. The isolation technique appeared to have no effect on the differentiation process. The calvaria could be used several times as explant cultures for a reliable source of differentiating osteoblast-like cells. The cultures kept in DMEM had a significantly higher DNA content, but significantly less alkaline phosphatase activity (ALP) per DNA and protein per DNA content than the BGJb cultures. Monolayer cultures had a significantly higher DNA content than the micromass cultures, in both growth media. Furthermore, the micromass culture had a significantly higher ALP per DNA than monolayer cultures at 1 week. The morphology of all cell cultures at 3 weeks reflected the biochemical results. Only the cells grown in BGJb formed abundant ALP positive and mineralized nodules in monolayer cultures. In contrast, cells grown as micromasses formed a dense calcified area, independently of the growth medium used. DMEM promoted the proliferation, whereas BGJb stimulated the differentiation of osteoblast-like cells in monolayer cultures. Micromass cultures were less sensitive to nutritional conditions than monolayer cultures and promoted the differentiation of osteoblast-like cells.

Journal Article↗

Stem cell transplantation for autoimmune diseases.

Much progress has been made in the field of haemopoietic stem cell transplants (HSCTs) for severe autoimmune disorders. Theoretical considerations, animal data and anecdotal evidence suggested some time ago that intensive immunoablation followed by autologous HSCT could restore normal immune reactivity in patients with severe autoimmune disorders. Based on a concept statement issued in 1995, two European societies, the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) began collecting phase I/II trial data in an international collaborative network. Sufficient information from more than 350 patients allows a preliminary assessment with level three evidence. Autologous HSCTs can induce remissions in all disease categories tested so far. Remissions can be transient or durable. HSCTs are associated with significant morbidity and mortality. Treatment-related mortality (TRM) is near 10% at 1 year and is associated with the intensity of the conditioning and the stage of the disease at the time of transplant. Marked interdisease differences exist. There are few data available in haematological autoimmune diseases, more in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA) and multiple sclerosis (MS). Patient selection has been recognized as a crucial element from the phase I-II trials. Patients with advanced disease, severely compromised organ function or irreversible organ damage should not be considered as candidates for HSCT. Prospective randomized studies should now determine the value of HSCT compared to standard therapy. Such trials are ongoing for patients with systemic sclerosis (ASTIS trial--Autologous Stem Cell Transplantation International Scleroderma Trial) or are planned for patients with multiple sclerosis (ASTIMS trial--Autologous Stem Cell Transplantation International Multiple Sclerosis Trial) and rheumatoid arthritis (ASTIRA trial--Autologous Stem Cell Transplantation International Rheumatoid Arthritis Trial). More phase II data are needed for other indications such as SLE and JIA.

Animals↗

[Wound infections after heart surgery interventions--a cost analysis].

Decreasing financial resources in the health care system require effective cost management. For this reason and due to special modalities of reimbursement regulations for open heart procedures, we analyzed the extent of additional costs caused by subsequent deep wound infections requiring surgical revision. The real costs of 12 consecutive cases of sternal infections out of a total of 1,124 open heart procedures in 1996 were assessed and differentiated.

Cardiac Surgical Procedures↗

Autopsy study of the elderly institutionalized patient. Review of 234 autopsies.

Autopsies are performed much less frequently in the elderly than in younger patients. Little information exists as to causes of death in the institutionalized elderly. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 234 patients who died during a 14 1/2-year period at our chronic care institution to determine the accuracy of clinical cause of death in addition to the pathologic cause of death. The most common causes of death included bronchopneumonia (33%), congestive heart failure (15%), metastatic carcinoma (14%), pulmonary embolism (8%), myocardial infarction (7%), cerebrovascular accident (6%), unknown cause of death (8%), and a miscellaneous group (9%). The highest diagnostic error rate was in the underdiagnosis of pulmonary embolism (39% antemortem accuracy rate). The most accurately diagnosed condition was cerebrovascular accident (92% antemortem accuracy rate). Pneumonia was correctly diagnosed antemortem in 73% of the patients studied. These data suggest that serious and potentially treatable illnesses are underdiagnosed in the elderly institutionalized patient and that there is valuable information to be learned by performing autopsies in the elderly population.

Aged↗

Anticipatory grief and aged widows and widowers.

The purpose of this investigation was to explore the preventive value of anticipatory grief on the medical adjustment of the aged bereaved. Data were collected for 81 surviving widows and widowers 6 mo. after their loss. Sixteen of the bereaved had spouses who died of a chronic illness. These two groups were compared on three criteria of medical adjustment: physician office visits, feeling ill without contacting a physician, and use of psychotropic medications. The data indicated that the aged bereaved of a lengthy chronic fatal illness did worse than the bereaved of a shorter chronic illness death. By sex, no significant differences were found between widows and widowers of a short-term illness death. However, differences were noted for the chronic illness category, and within this category for length of chronicity. In both cases widowers showed more medical problems than widows.

Acute Disease↗