1,720,969 research outputs found
Successful management of malaria tropica with 50% parasitaemia
No full textHistory: A 52-year-old woman was hospitalized with fever after a 3-week stay in tropical Kenya. Prophylaxis against malaria had been carried out with chloroquine. Diagnosis: Falciparum malaria with 28% parasitaernia at first examination, rising to 50% after 3 hours. Treatment and course: Treatment with quinine dihydrochloride i.v. was initiated immediately after diagnosis. In addition, in view of increasing parasitemia of up to 50%, a partial exchange blood transfusion was carried out. No clinical signs of organ damage caused by malaria were observed. Because of a drop in blood pressure the patient needed catecholamine treatment for a short time. After decrease of the parasiterma the patient rapidly recovered and complete cure was achieved. Conclusion: Despite extremely high parasitemia the clinical signs were unusually mild. Standard treatment for severe malaria is intravenous administration of quinine. However, this drug is no longer sold in Germany, so that difficulty in obtaining it must be expected. A stockpiling of quinine is recommended for hospitals treating patients with malaria. Transfusion may improve outcome and must be considered if parasite counts are high or if there are clinical signs of malaria complications
Ten Years of Treatment with 400 mg Imatinib per Day in a Case of Advanced Gastrointestinal Stromal Tumor
No full textImatinib mesylate, as treatment for gastrointestinal stromal tumors (GIST), has dramatically changed the prognosis for survival – not only because it is efficacious, but also because it attracted attention to this malignant disease. GIST is now a well-known disease entity and a paradigm for targeted therapies in malignant diseases. A now 74-year-old patient presented with recurrence of a primary duodenal GIST (initial diagnosis and primary resection in 1998; diameter 10 cm, KIT exon 11 mutation, PM V559D) and liver metastasis after a second surgical resection was performed in 2000. Conventional chemotherapy with adriamycin and ifosfamide failed to control growth of the relapsed tumor and liver metastasis. In July 2001, compassionate use of imatinib was started. Tumor regression was observed at continuous follow-ups (every 2 months for the first 6 months, and 6 months thereafter) and persisted until now. The patient’s physical performance has remained in good condition. Side effects consisted of periorbital edema and sudden muscle cramps of toes and fingers, pain of bones and joints, an intentional tremor, a paler color of the skin, as well as a slight anemia. Imatinib is the first orally administered anticancer drug. Our case shows that a sustained response is possible with continuous therapy over a long time, if the drug is well tolerated. This implies a high compliance of the patient and suggests that resistance to imatinib does not have to develop. Exon 11 (point) mutation might not only represent a positive predictor for imatinib response in general, but especially for imatinib response on long-term
Exocrine pancreatic function in patients with end-stage renal disease
No full textAim: Malnutrition is a common problem in patients with end-stage renal disease (ESRD). Several studies showed 30 years ago that more than half of patients with ESRD suffered from exocrine pancreatic insufficiency. However, the studies never investigated whether the functional impairments led to morphological changes of the pancreas or to steatorrhea and thus indicating the need for lifelong pancreatic enzyme substitution. Our goal was therefore not only to establish the frequency but also the severity of exocrine pancreatic insufficiency in hemodialysis patients. Methods: The study included 50 hemodialysis patients with no history of acute or chronic pancreatitis or upper abdominal symptoms of uncertain origin. All patients with hyperthyroidism, status post-gastrectomy or (partial) small bowel resection, or chronic inflammatory bowel disease were excluded. In all 50 patients, fecal elastase-1 was determined using two different methods (Bioserv Diagnostics and ScheBo Biotech) and fecal fat content and fecal weight were measured. Results: Mild to moderate exocrine pancreatic insufficiency (elastase-1 100 - 200 mu g/g stool) was found in 10% of patients. It was not correlated with age, sex, and underlying renal disease, duration of hemodialysis, or diarrhea and steatorrhea. In no patient was the enzyme content < 100 mu g/g stool, i.e., it never sank to a level at which pancreatic enzyme substitution would have been recommended. Nine patients (18%) had mild diarrhea (200 - 300 g stool/day), and 10 (20%) had mild steatorrhea (7 - 15 g fat/day in the stool). Five patients had both diarrhea and steatorrhea. Conclusions: Mild to moderate but not severe exocrine pancreatic insufficiency is not infrequent in patients on hemodialysis but unlikely to be responsible for malnutrition in ESRD. Non-pancreas-related steatorrhea is also not uncommon. This finding requires further analysis because steatorrhea might influence nutrition, thus potentially opening the way to new therapeutic approaches
Long-lasting complete response of metastatic melanoma to ipilimumab with analysis of the resident immune cells
No full textEven though ipilimumab is a promising antibody used for stage IV melanoma therapy, the response varies and is difficult to predict. We here report on a case of successful treatment with ipilimumab in dacarbazine-resistant metastatic malignant melanoma, including a review of the literature on the long-term treatment results. A 62-year-old patient with a history of a resected lentigo-maligna melanoma 5 years earlier and parotideal metastasis 1 year before was admitted with a newly detected 3.5 cm liver metastasis. Atypical liver resection was performed (R1) Immunohistochemically, CD3+ T-lymphocytes and CD68+ macrophages were detected at the tumour margins and within the parotideal and hepatic melanoma metastases. A sub-analysis of the liver metastasis showed scattered FOX-P3+ regulatory T-lymphocytes as well as multiple CD8+ effector T-cells. Chemotherapy with dacarbazine 1,000 mg/m(2)/day was administered at 4-weeks intervals for 3 months. A follow-up positron-emission computed tomography and liver biopsy revealed melanoma metastases in the liver, lungs, and mediastinum. Compassionate use of ipilimumab was administered at 3 mg/kg every 3 weeks for a total of four doses. After an initial increase in tumour size, most lesions responded, but progressive axillary and cervical lymphadenopathy was observed before complete remission was achieved. Side effects included fatigue, dyspnoea, cough, upper abdominal pain with diarrhoea, and gingival hyperplasia. Now, 36 months after ipilimumab therapy and 8 years after the initial melanoma diagnosis, the tumour did not recur. It would be challenging to hypothesize that long intervals between diagnosis and need for treatment, clinical side effects, an initial increase in tumour size and the presence of intra-tumoural T-cells and macrophages might predict tumour response
Pharmacokinetics of Meropenem in Critically Ill Patients With Severe Infections
No full textBackground: Meropenem is an effective beta-lactam antibiotic that is frequently used to treat serious infections in both intensive care unit (ICU) and febrile neutropenic hematology/oncology (Hem/Onc) patients. Studies suggest that to be effective, meropenem concentrations must be maintained above the inhibitory concentrations for the majority of a dosing interval. However, the pharmacokinetics (PK) of meropenem seem to differ in critically ill patients compared with healthy or less ill subjects used to select labeled dosing regimens. Objectives: This study was designed to investigate meropenem PK in critically ill patients and to see how often standard dosing regimens produced adequate plasma concentrations. A secondary objective was to investigate how achieved concentrations were related to outcomes (morbidity and mortality) in these patients. Methods: Meropenem plasma concentrations over time were measured using a high pressure liquid chromatography assay in febrile Hem/Onc and ICU patients who were treated with standard meropenem dosing schedules. Outcomes such as fever control and survival were assessed in these patients and compared with individual meropenem PK data and with recommended target concentrations. Results: A total of 25 subjects including 10 febrile Hem/Onc and 15 ICU patients with a variety of serious illnesses and baseline renal function were studied. Mean peak concentrations were less variable than were pre-dose concentrations. Post peak and trough concentrations were often below recommended minimum inhibitory concentrations. Both clearance and volumes of distribution were greater than reported in less ill subjects, only in part explained by increased renal clearance. Therefore, serum concentrations often did not exceed recommended concentration targets even for moderately sensitive organisms. Inadequate concentrations were especially common in the mostly ill, febrile neutropenic Hem/Onc subjects and seemed to explain at least some therapeutic failures. Conversely, drug accumulation occurred in ICU subjects with decreased renal function. Conclusions: Standard meropenem dosing regimens were inadequate in many critically ill febrile, neutropenic Hem/Onc, and septic ICU patients. These data suggest a role for meropenem concentration monitoring in such patients
Effects of different proton pump inhibitors on cardiac contractility in isolated human failing myocardium
No full textAim. Proton pump inhibitors (PPI), e.g. pantoprazole (PP), esomeprazole (EP) and omeprazole (OP), work as anti-ulcer/gastrointestinal reflux drugs. Also, they are widely used in postoperative care of patients in cardiac surgery to prevent upper gastrointestinal bleeding. Therefore, in western industrial countries they play a major economic role, representing one of the most important drugs in open heart cardiac surgery. Methods. Intact muscle strips (n=32) were isolated from the right ventricle wall of failing human hearts. In four different groups (PP, EP, OP, control group, each n=8), force amplitudes were recorded at a frequency of 60 beats per minute (bpm) with increasing PPI concentrations (0 to 320 mu m/mL). Results. In isometrically contracting muscle strips, significant negative inotropic effects were observed in the presence of all three PPI-groups (PP, EP and OP) with doses of 2.5 mu g/mL and higher compared to the control group (p < 0.05 each). With high doses (320 mu m/mL), force amplitudes could be almost completely depressed. The half maximal inhibitory concentration (IC(50)) for EP was 35.7 (confidence interval: 17.3-73.6) vs. OP 29.3 (6.8-126.6) vs. PP 25.1 (14.6-43.1) mu g/mL (n.s.). No significant differences were found between the different proton pump inhibitors (PP, EP, OP) throughout the range of all concentrations. Relaxation was unpaired in all PPI subgroups with prolonged time to 90% relaxation (RT90%) and maximum relaxation velocity (-df/dt) was reduced, too. These effects were partially reversible after wash-out of the drugs. Conclusion. We conclude that proton pump inhibitors show significant negative inotropic effects on isolated human failing myocardium. There is no apparent difference seen in the magnitude of the effects of each PPI-group. Further, in-vivo investigations are necessary to reveal the clinical evidence of PPI's negative inotropic effects, e.g. in cardio-surgical patients with heart failure
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