To describe the pharmacokinetics, safety, and efficacy of twice-daily indinavir + ritonavir regimens
A cohort-based survey of HIV-infected patients who either used indinavir 800 mg + ritonavir 100 mg ...twice daily or indinavir 400 mg + ritonavir 400 mg twice daily.
Data were extracted from a database of samples sent to our laboratory for measurement of indinavir + ritonavir plasma concentrations. Patient characteristics, safety, and efficacy measurements were collected by retrospective chart review.
100 Patients using 800-mg indinavir + 100-mg ritonavir twice daily and 32 patients using 400-mg indinavir + 400-mg ritonavir twice daily were eligible. Median peak and trough concentrations of indinavir were 6.8 and 0.77 mg/L in the 800/100 group and 2.6 and 0.45 mg/L in the 400/400 group. The most frequently found side effects were nausea and vomiting, which occurred in 22.1% and 34.9% of the patients in the 800/100 and the 400/400 groups, respectively. Viral load data were analyzed for patients who switched from 800-mg indinavir three times daily to one of the indinavir + ritonavir twice daily regimens. At the time of switch 63% (800/100 group) and 60% (400/400 group) had an undetectable viral load and this increased to 77% and 70%, respectively, during follow-up. Patients who switched to the 400/400 group discontinued treatment more frequently than patients who switched to the 800/100 group (70% vs. 26%, p =.008).
Indinavir + ritonavir regimens show improved pharmacokinetic properties, allowing twice-daily dosing with food. Clinical data suggest that safety and efficacy is at least as good as with indinavir three-times-daily regimens without ritonavir. Prospective, comparative trials are needed to properly assess the role in HIV therapy of these twice-daily indinavir + ritonavir regimens.
Background Wernicke encephalopathy can have different clinical outcomes. While infections may precipitate the encephalopathy itself, it is unknown if infections also modify the long-term outcome in ...patients developing Korsakoff syndrome. Objective To determine whether markers of infection such as white blood cell counts and absolute neutrophil counts in the Wernicke phase are associated with cognitive outcomes in the end-stage Korsakoff syndrome. Method Retrospective, descriptive study of patients admitted to Slingedael Korsakoff Center, Rotterdam, the Netherlands. Hospital discharge letters of patients with Wernicke encephalopathy were searched for relevant data on infections present upon hospital admission. Patients were selected for further analysis if data were available on white blood cell counts in the acute phase and at least one of six predefined neuropsychological tests on follow-up. Results Infections were reported in 35/68 patients during the acute phase of Wernicke-Korsakoff syndrome: meningitis (1), pneumonia (14), urinary tract infections (9), acute abdominal infections (4), sepsis (5) and/or empyema (1), and infection ‘of unknown origin’ (4). The neuropsychological test results showed significant lower scores on the Cambridge Cognitive Examination (CAMCOG) non-memory section with increasing white blood cell counts (Spearman’s rank correlation, Rho = -0.34; 95%-CI: -0.57−-0.06; 44 patients) and on the ‘Key Search Test’ of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) with increasing absolute neutrophil counts (Rho = -0.85; 95%-CI: -0.97−-0.42; nine patients). Conclusions Infections may be the presenting manifestation of thiamine deficiency. Wernicke-Korsakoff patients who suffered from an infection during the acute phase are at risk of worse neuropsychological outcomes on follow-up.
The reproducibility of the binary typing (BT) protocol developed for epidemiological typing of
Staphylococcus aureus was analyzed in a biphasic multicenter study. In a Dutch multicenter pilot study, ...10 genetically unique isolates of methicillin-resistant
S. aureus (MRSA) were characterized by the BT assay as presented by van Leeuwen et al. J. Clin. Microbiol. 2001 39 (1) 328. The BT assay, including a standardized DNA extraction protocol was performed in duplicate in eleven medical microbiology laboratories. Two different hybridization detection procedures were applied and a prelabeled DNA sample as process control was included. Only three laboratories accurately identified all strains. Divergence in technical procedures resulted in misinterpretation due to an increasing number of faint or absent hybridization signals in combination with high background staining. The binary type of the process control was determined correctly by all participating laboratories. The feasibility of the BT protocol was related directly to the skill of the laboratory personnel. On the basis of the national study, we concluded that the DNA extraction protocol needed modification to improve DNA yield and purity.
Subsequently, seven European laboratories participated in an international study to determine the reproducibility of the modified BT protocol. Each center was asked to analyze 10 DNA samples previously extracted from 10 MRSA strains (phase 1) and, additionally, to analyze 10 MRSA strains, using the standardized or their in-house DNA isolation protocol (phase 2). A prelabeled DNA process control sample was included again. The binary types of all DNA samples were identified correctly by all but one laboratories. This latter laboratory diverged from the protocol by adding an excess of labeled DNA to the hybridization mixture, resulting in a high background and, therefore, noninterpretable BT results. All centers produced identical BT results for the process control. Five of the seven centers correctly identified the binary types of all 10 MRSA strains in phase 2 of the international study. Three of these centers used their in-house DNA extraction protocol. Divergence from the standard BT protocol in the remaining two centers resulted in no interpretable BT data for the 10 MRSA strains. The study demonstrated that each center that followed the BT protocol to the letter could generate reproducible results, irrespective whether or not an in-house DNA isolation protocol was used. The current BT protocol thus represents a simple method generating robust, reproducible genotype data for
S. aureus strains.
To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-11C)-tyrosine by 11C-carboxylation of the appropriate ...alpha-lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-11C)-Tyrosine in 0.1 N NaH2PO4 buffer was prepared with a radiochemical yield of 8%-16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-11C)-tyrosine in physiological saline was obtained in 2%-4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-11C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.
The effect of combination chemotherapy on human small intestinal morphology and disaccharidase activities and their relation with clinical and chemical (fecal wet weight and K‐excretion) parameters ...for gastrointestinal toxicity were evaluated in patients with disseminated malignant melanoma receiving enteral normoalimentation (NA). Also evaluated were the supposed protective effects on gastrointestinal toxicity of enteral hyperalimentation (HA) with an elemental diet. After chemotherapy, a comparable decrease in villus height, total mucosal height, and mitotic index was found in jejuna biopsy specimens of both groups. However, in the NA group, the crypt depth decreased (in contrast to the HA group), whereas the disaccharidase activities in the HA group deteriorated to lower values than in the NA group. The authors found no correlation between disaccharidase levels and mucosal morphology, nor was there a correlation between these variables, fecal parameters and clinical diarrhea, suggesting that diarrhea occurring after chemotherapy was not due to loss of mucosal tissue or decrease in enzyme activities. A protective effect of HA with an elemental diet on gastrointestinal toxicity could not be established.
The density of H-2K antigens was determined on both the mouse hemopoietic stem cell, using an assay for spleen colony-forming units (CFU-S), and the prothymocyte, using a thymus repopulation assay. ...This was done by light-activated cell sorting of bone marrow cells labeled first with a biotinylated antibody against H-2Kk and then with avidin-fluorescein isothiocyanate. Almost all CFU-S were found to be present among the 4% bone marrow cells with high forward light scatter (FLS), low perpendicular light scatter (PLS), and bright immunofluorescence. Thymus regeneration by this brightly fluorescent fraction was delayed 3 days compared to thymus regeneration by unsorted cells, although the same number of CFU-S was present in each cell suspension. This delay indicates that differentiation from CFU-S to prothymocytes takes 3 days. The fraction of cells in the FLS/PLS window with dull anti-H-2Kk fluorescence contained few CFU-S and gave rise to a transient thymus regeneration. These findings indicate that the prothymocyte carries fewer H-2K antigens than does the CFU-S. The H-2K antigen is a marker with which CFU-S and prothymocytes can be separated. Therefore, during early T-cell differentiation, the number of H-2K molecules on the cell surface decreases (CFU-S---prothymocyte---cortical thymocyte). During maturation of T cells, a reexpression of H-2K molecules occurs, since lymph node cells and spleen cells were shown to be brightly positive for H-2K antigen.
A number of clinical and chemical parameters related to the gastrointestinal tract in patients treated with intensive chemotherapy for disseminated malignant melanoma were evaluated in order to find ...quantitative indicators for gastrointestinal toxicity and to investigate the cause of diarrhea after chemotherapy. In 11 patients 17 courses of polychemotherapy with bleomycin, DTIC, vindesine, and actinomycin D were administered, while the patients received complete liquid enteral nutrition. As clinical parameters for toxicity the diarrhea grading system according to the WHO criteria and the daily fecal consistency were used. Furthermore, in the feces Na+, K+, and Cl- (mmol/24 h), Na+/K+ ratio, dry and wet weight (g/24 h), lactate and bile acids (mmol/24 h), fat (g/24 h), pH, and osmolarity were determined. Both clinical parameters were closely correlated. The most important effects of the chemotherapy on the chemical parameters were an increased fecal fluid, K+, and fat excretion. The fecal wet weight and K+ excretion showed a high correlation with the two clinical parameters for gastrointestinal toxicity. We conclude that mucosal injury resulting from chemotherapy probably leads to increased small intestinal fluid and electrolyte secretion inducing diarrhea and that fecal wet weight and K+ excretion are probably the best quantitative indicators for gastrointestincal toxicity.
Provider: - Institution: Museum Catharijneconvent - Data provided by Europeana Collections- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 ...Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Provider: - Institution: Museum Catharijneconvent - Data provided by Europeana Collections- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 ...Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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