Persistent hypercalcemia leading to acute pancreatitis in a patient with relapsed myeloma and renal failure.
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Biomedical subjects
Publications and source records attributed to I Celik.
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Chemotherapy options for resistant advanced-stage sarcomas are limited and in most cases disappointing. In a phase II study, we treated 26 consecutive patients with refractory advanced sarcoma with ifosfamide and etoposide combination chemotherapy. All patients had received prior doxorubicin- and/or cyclophosphamide-based chemotherapies. Seventeen patients were male and 9 were female. The patients' median age was 35 years (range: 19-67 years). A total of 24 patients were eligible for evaluation of responses. Seven patients had a complete response (CR) (29.1%), 3 had a partial response (PR) (12.5%), 3 had stable disease (SD) (12.5%), and 11 had progressive disease (PD) (45.9%). An overall 41.6% objective response was achieved. Median time to treatment failure was 13.3 months. A total of 108 cycles of therapy were evaluable for evaluation of toxicity. Myelosuppression, observed in 55.5% of the treatment courses, was the major dose-limiting toxicity. Nausea and vomiting, seen in 64% of the courses, were the most important nonhematological side effects. Alopecia was almost universal. Hemorrhagic cystitis was observed in only 1 patient. We have concluded that the combination of ifosfamide, mesna, and etoposide is effective in advanced refractory sarcomas, and has acceptable toxicity.
In a clinic modelling randomised trial (CMRT) in three groups of 10 land-race pietren pigs each it could be shown that the influence of prophylactic antibiotic administration on intraoperative hemodynamic stability and histamine release is only evident, if by stepwise addition of complicating factors the overall complexity of the experimental setting is increased. Different antibiotic regimen for prophylaxis significantly affected the incidence of cardiovascular instabilities only after relevant blood loss, restoration of circulation and subsequent submaximal induction of anaphylactoid reactions by the histamine liberator Polymyxin B. In conclusion, preclinical testing of therapeutic agents in complex clinic modelling randomised trials should be mandatory to avoid the possible hazards of misconducted clinical trials.
The perioperative changes in epinephrin-, norepinephrine-, histamin-, C5a- and interleukin-6-levels were studied in 40 patients undergoing cholecystectomy for the diagnosis of acute cholecystitis. All relevant mediator levels could be determined in 38 patients. The outcome was not optimal in 16 of them (42%). In order to evaluate the predictive value of the mediators under investigation for the quality of the patients' outcome, a model based on the Bayes' theorem was developed. Using this model the outcome (optimal vs. not optimal) could be correctly predicted in 30 (79%) of our study patients. This kind of data analysis allows to define states of increased risk for a not optimal recovery based on biochemical parameters.
In clinical reality the drugs used for H1/H2-prophylaxis are not restricted to the combination of dimetinden/cimetidine, also only for this combination the effectiveness for preventing severe cardiorespiratory disturbances is proven in a randomised controlled clinical trial. However, it is almost impossible to conduct such an extended clinical trial in order to check all possible combinations. Instead of this, we developed a complex animal model featuring clinical variability and the principles of a well conducted randomised controlled clinical trial (CMRT = clinic modelling randomised trials), to evaluate different H1/H2 combinations. In this CMRT in pigs (four groups of 15 animals), the H1/H2 combination of dimetinden/cimetidine and dimetinden/famotidine showed an effectiveness similar to the randomised clinical trial. With dimetinden/ranitidine no significant prophylactic effect was observed. Two conclusions can be drawn: (1) CMRTs in animals are able to answer relevant clinical and research questions that otherwise only could be solved by clinical studies and may be a successful intermediate between basic research and clinical trials. (2) Drugs, even of the same substance class, may not be simply exchangeable. Hence, before changing a proven medication, trials in an adequate complex animal model (CMRT) should be mandatory.
OBJECTIVE: To compare plasma concentrations of soluble P-selectin (sP-selectin) in patients with rheumatoid arthritis (RA) and thrombocytosis with those with RA with normal platelet counts and healthy controls, and to explore the relationship between clinical and serological measures of disease activity. METHODS: Nineteen patients with RA with marked thrombocytosis, 20 with normal platelet counts, and 24 controls were enrolled. Ritchie articular index and morning stiffness were recorded as clinical markers of disease activity. Blood samples were collected for platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma sP-selectin determinations. Correlations between sP-selectin and clinical and serological markers of disease activity were noted. RESULTS: Patients with RA and thrombocytosis compared to patients with normal platelet counts showed evidence of more active disease when ESR, CRP, morning stiffness, and Ritchie articular index were considered. The thrombocyte count in patients with RA with marked thrombocytosis revealed a positive correlation with CRP and Ritchie articular score. Plasma sP-selectin levels were found to be significantly higher in patients with RA compared to controls. sP-selectin levels were significantly higher in patients with RA with thrombocytosis compared to those with normal platelet counts, and positive correlations were observed between plasma sP-selectin levels and Ritchie index, morning stiffness, and thrombocyte counts in those patients. CONCLUSION: Elevated plasma sP-selectin levels in RA could indicate the presence of a continuous underlying inflammatory stimulus. In addition, the augmented increase in patients with RA and thrombocytosis and its correlation with clinical activity may imply the cytokine-adhesion molecule interaction mediates the chronic inflammation of RA.
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Risk research and risk analysis have to be modeled as a fairly complex system including multivariate regression modeling for risk factors in etiology, Markov models in pathogenesis, and a construct of mechanistic and hermeneutic variables for clinical outcome analysis. The McPeek index is proposed as an example. Several prophylaxes for risk reduction in the perioperative period produce risk reduction as well as risk augmentation in different types of outcome. These unexpected findings were observed not only in clinical trials, but also in animal experiments and in isolated tissues. This demonstrates a basic problem of handling complexity in the real clinical setting.
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The longitudinal muscle (LM) represents a strong muscular structure of the anal canal situated between the internal (IAS) and the external anal sphincter (EAS). Terminal fibres of this muscle insert at the submucosa of the anal canal, representing the m. canalis ani. Others cross the subcutaneous part of the EAS to become the m. corrugator ani. Thus, the LM connects the visceral and somatic parts of the anal sphincter complex. Histologically ganglionic cells and as Vater-Pacinian corpuscles can be identified inside the LM. Morphology, topography and histology of the LM suggest that this muscle participates in maintaining anorectal continence. It is mandatory that the exact functions of this muscular structure be to elaborated upon, if we are to understand the mechanism of anorectal continence.
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The aim of this study was to evaluate the response characteristics of vincristine, adriamycin and dexamethasone (VAD) as a first-line chemotherapy and to determine the efficacy of maintenance alpha-interferon (alpha-IFN) in multiple myeloma (MM). Between January 1985 and December 1994, a prospective trial was performed in stage II and III MM patients. The study population received only VAD with no maintenance therapy before 1990 (n=31), and those recruited after 1990 (n=33) were planned to be maintained with alpha-IFN (5 mU, 3 times per wk) during the plateau to a maximum of 2 yr. Median follow-up duration (44 vs. 39 months), time to response (3.4 vs. 3.5 months) and rate of objective response (61.3%, 19/31 and 63.6%, 21/33) were similar in VAD-only and VAD+IFN groups, respectively. The survival analyses revealed higher median progression-free (39.6 vs. 12 months) and overall survival (65+ vs. 24 months) durations in VAD+IFN group compared to VAD-only group. VAD regimen was well tolerated and IFN-related side effects were reversible. These findings denote that IFN maintenance prolongs the duration of response obtained by VAD.
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