Patients in the intensive care unit (ICU) are at risk for suboptimal levels of β-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum β-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT). MIC was used as the target and, when available, the actual MIC (MIC) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m. The rate of patients reaching 100% fT > MIC was higher (89%, 31/35) compared to the same patients using MIC (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MIC. Increased renal clearance was independently associated to not reaching 100% fT > MIC. On repeated sampling, >77% of patients had stable serum drug levels around the MIC. Serum concentrations of β-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.
With the aim of potentiating the anti-tumour effect of interferon in metastatic malignant melanoma by concomitant inhibition of suppressor T cells, oral cimetidine (histamine-2 receptor antagonist) medication was added to interferon (HuIFN-alpha(Le] therapy in a series of 20 patients. While no objective tumour responses were recorded with interferon treatment alone administered intramuscularly or intratumorally, six patients had objective tumour regressions on subsequent combined therapy. Five out of eight patients with metastases confined to skin and subcutaneous tissue had complete tumour regressions while one patient with skin and lung metastases achieved an extensive partial regression of the skin tumour and a complete roentgenological regression of the lung metastasis. Three additional patients attained a stable disease status for prolonged periods of time. Histopathological examinations confirmed disappearance and/or degeneration of melanoma cells and demonstrated a marked lymphocyte infiltration in tumour sites of the patients with objective tumour regression.
The authors undertook a controlled, prospective, randomized study of 171 patients with supratentorial astrocytoma Grades 3 and/or 4 (classified according to Kernohan). All patients were given chemotherapy consisting of procarbazine, vincristine, and lomustine (CCNU) (PVC). Half of the patients received whole-brain irradiation (RT) to a dose of 5800 cGy in the tumor-bearing hemisphere and 5000 cGy in the contralateral hemisphere. After diagnosis of progressive tumor growth, patients received individual treatment. The endpoint of the study was time to progression, but cases were followed until the patients died. Median time to progression (MTP) for the whole randomized population was 21 weeks. Median survival time (MST) was 53 weeks; 18% of patients survived for 2 years or longer. Survival analysis showed that patients less than 50 years of age treated with PVC plus RT had significantly longer MTP (81 weeks) and MST (124 weeks) than all other patients. For patients less than 50 years of age treated with PVC alone, MTP was 21 weeks and MST was 66 weeks. For patients more than 50 years of age treated with PVC plus RT, MTP was 23 weeks and MST was 51 weeks; in the PVC group, MTP was 17 weeks and MST was 39 weeks. Age, Karnofsky index, areas of Grade 2, and absence of extensive necrosis in the tumor were significant prognostic factors in the univariate analyses. Patients less than 50 years of age treated with PVC plus RT had significantly longer survival (P = 0.037) when correcting for these factors in a multi-variate analysis. Cancer 68:22-29, 1991. RIMARY MALIGNANT BRAIN TUMORS constitute a P considerable therapeutic problem. Median survival time after surgical resection and conventional care varies from 4 to 6 rn0nths.I-j These tumors are only moderately sensitive to radiation therapy, and a limited number of From the Departments of *Neurology. tOncology. +Neurosurgery. §Pathology, and IlDiagnostic Radiology, and llthe Southern Swedish Regional Turnour Registry, University Hospital, Lund, and the #Depart-ment of Oncology, General Hospital, Malmo, Sweden.
The motility in the first part of the duodenum has been studied by a method combining roentgen fluorography and multiple pressure recordings in 7 normal volunteers, in 7 patients having gastric, and in 7 having duodenal, ulcer. A significantly lower number of retrograde motor sequences was found in cases with duodenal ulcer than in normals, while patients with gastric ulcers showed no such difference. This abnormality in subjects with duodenal ulcer was interpreted as a deficiency in the transport of neutralized duodenal contents from more distal parts of the duodenum up into the bulb. The abnormality can explain the earlier known lower pH in the duodenal bulb in subjects with duodenal ulcer and contribute to the pathogenesis of the disease.
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