Pyronaridine against multiresistant falciparum malaria.
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Antimalarials↗
Biomedical subjects
W Peters
Publications and source records attributed to W Peters.
Silicon and silicone levels in patients with silicone implants.
Although a potential link between silicone gel breast implants and autoimmune connective tissue disease has been suggested, none has been proven. The potential role of silicone as an immune adjuvant remains very controversial. Currently available techniques do not easily allow precise measurements of silicone in tissues. However, all compounds containing silicon (which would include silicone) can be measured accurately. The present study was designed to measure silicon levels in the fibrous capsules of patients with silicone-gel breast implants, saline breast implants and silicone inflatable penile prostheses. Baseline control silicon levels were obtained from the breast tissue of patients undergoing breast reduction, who had no exposure to breast implants. All silicon measurements were carried out using atomic absorption spectrometry with a graphite furnace. The mean silicon levels in 16 breast tissue control samples from 8 patients undergoing breast reduction varied from 0.046 to 0.742 micrograms/g dry weight, with the median mean being 0.0927. The median silicon level in capsules from 6 patients with saline implants was 7.7 micrograms/g (range 36.6). The median silicon level in capsules from 5 patients with silicone inflatable penile prostheses was 19.5 micrograms/g (range 34.8). Although the levels of silicon in capsules of patients with saline breast prostheses and penile implants were higher than in control samples, they were much lower than those from the capsules of the 58 gel implants (median 9979 micrograms/g). Of the 58 silicone gel breast implants (from 20 patients with bilateral implant removal and 18 patients with unilateral removal) which had been inserted from 1974 to 1990, 28 were intact, 8 had pinhole leaks, and 22 were ruptured. Median capsule silicon levels and ranges for all 58 implants, for intact only, for leaking, and for ruptured were: 9979 (152,000), 10,477 (88,703), 6592 (65,396), and 9922 (152,387) micrograms/g respectively. There were no significant differences in silicon levels associated with implant status, duration in situ, or year of implantation. Capsule contracture was not associated with higher levels of capsule silicon. Capsule silicon levels were about 10(6) times higher than previously assayed blood silicon levels. This may be because silicone released from implants remains localized in capsular tissue, or because blood-borne silicone is quickly excreted. Using 29Si nuclear magnetic resonance spectroscopy, no detectable silicone was found in the blood of 7 control women and 7 women with silicone-gel implants (5 with known implant rupture).
Breast Implants↗
Silicon capsule assays with low-bleed silicone gel implants.
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Breast Implants↗
Evolution of late potentials during the first 8 hours of myocardial infarction treated with thrombolysis.
It has been demonstrated that successful thrombolytic therapy is associated with a reduction of late potentials in the signal-averaged electrocardiogram (SAECG) recorded within 48 hours after hospital admission. This study extends these observations, using for the first time a longitudinal design investigating whether ischemia and its potential reversal by thrombolytic therapy are associated with dynamic changes in SAECG recordings obtained continuously for 8 hours after the start of therapy in patients with acute myocardial infarction (MI). SAECGs were obtained from 12 patients (2 women and 10 men; ages 63 +/- 13 years) with acute MI. The SAECG (X2 + Y2 + Z2)1/2 was generated with a high pass filter of 40 Hz, noise < or = 0.3 microV. Comparing the SAECG recordings during the first and eighth hours, there was a significant decrease in filtered QRS duration (fQRS; 119.5 +/- 17.1 vs 106.3 +/- 15.3 ms) and duration of the low amplitude signals < or = 40 microV of the terminal QRS (LAS40; 48.8 +/- 18 vs 34.2 +/- 14.2 ms), and increase of root mean square voltage of the last 40 ms of the QRS (t-RMS; 14.8 +/- 9.3 vs 37.8 +/- 34.4 microV) (rank test, P < or = 0.05). In this patient series, there was a significant improvement of fQRS, t-RMS, and LAS40 during the first 8 hours of acute MI, perhaps indicating reversal of ischemia with thrombolysis. Even during acute MI, these markers of delayed conduction allow investigation of intervention induced changes in myocardial conduction and possibly prediction of the patency of the infarct related artery using signal-averaging techniques.
Action Potentials↗
4-aminoquinoline analogs of chloroquine with shortened side chains retain activity against chloroquine-resistant Plasmodium falciparum.
We have synthesized several 4-aminoquinolines with shortened side chains that retain activity against chloroquine-resistant isolates of Plasmodium falciparum malaria (W. Hofheinz, C. Jaquet, and S. Jolidon, European patent 94116281.0, June 1995). We report here an assessment of the activities of four selected compounds containing ethyl, propyl, and isopropyl side chains. Reasonable in vitro activity (50% inhibitory concentration, < 100 nM) against chloroquine-resistant P. falciparum strains was consistently observed, and the compounds performed well in a variety of plasmodium berghei animal models. However, some potential drawbacks of these compounds became evident upon in-depth testing. In vitro analysis of more than 70 isolates of P. falciparum and studies with a mouse in vivo model suggested a degree of cross-resistance with chloroquine. In addition, pharmacokinetic analysis demonstrated the formation of N-dealkylated metabolites of these compounds. These metabolites are similarly active against chloroquine-susceptible strains but are much less active against chloroquine-resistant strains. Thus, the clinical dosing required for these compounds would probably be greater for chloroquine-resistant strains than for chloroquine-susceptible strains. The clinical potential of these compounds is discussed within the context of chloroquine's low therapeutic ratio and toxicity.
Aminoquinolines↗
Failure of 29Si NMR to detect increased blood silicon levels in silicone gel breast implant recipients.
We have compared directly the results of atomic absorption (AA) spectroscopy and a 29Si magic angle spinning (MAS) nuclear magnetic resonance (NMR) technique reported in the literature by Garrido et al. (Garrido, L.; et al. Magn. Reson. Med. 1994, 31, 328-330) for analyzing blood silicon levels in control patients versus patients with silicone gel breast implants. AA spectroscopy yielded blood silicon levels in the nanogram per milliliter range for control patients, while somewhat higher values were found in patients with implants. The 29Si MAS NMR technique applied to the identical blood samples was unable to detect silicon in any of the samples. Sensitivity calculations demonstrate that 29Si MAS NMR should not be expected to detect silicon at the levels determined by AA spectroscopy under the spectroscopic conditions employed and that the concentration of silicon-containing compounds would need to 10(4) times the level detected by AA in order to be detected by this NMR method.
Breast Implants↗
Co-localization and functional coupling of creatine kinase B and gastric H+/K(+)-ATPase on the apical membrane and the tubulovesicular system of parietal cells.
Immunogold labelling of creatine kinase B (BB-CK) and gastric H+/K(+)-ATPase in the parietal cells of the stomach revealed colocalization of these two enzymes on the apical membrane and the membranes of the tubulovesicular system. Upon fractionation of hog parietal cells, a specific fraction of the BB-CK proteins remained associated with the purified vesicles, in which gastric H+/K(+)-ATPase is highly enriched. The BB-CK present in this highly purified preparation was able to support pronounced H+/K(+)-ATPase activity in K(+)-loaded vesicles in the presence of phosphocreatine and ADP, although only low levels of ATP were measured. In contrast, when pyruvate kinase, phosphoenolpyruvate and ADP were used as an ATP-generating system to sustain similar levels of H+/K(+)-ATPase activity, ATP levels were more than 10-fold higher. Changing the experimental conditions such that ATP levels were the same for both systems resulted in significantly elevated H+/K(+)-ATPase activities in the BB-CK/phosphocreatine system in comparison with the pyruvate kinase/phosphoenolpyruvate system. These results indicate that gastric H+/K(+)-ATPase has preferential access to ATP generated by creatine kinase co-localized on the membranes of the vesicles.
Adenosine Diphosphate↗
Tissue- and cell-specific distribution of creatine kinase B: a new and highly specific monoclonal antibody for use in immunohistochemistry.
A synthetic 17-mer peptide corresponding to an unique sequence in the amino-terminal region of human creatine kinase B was used to raise a new and highly B-subunit-specific monoclonal antibody, CK-BYK/21E10. We show here that the monoclonal antibody is suitable for immunohistochemistry of unfixed frozen sections as well as formaldehyde- or Bouin-fixed, paraffin-embedded sections of human, rabbit, and mouse tissues. Moreover, in the study of cell- and tissue-specific distribution patterns, parallel Western blot analysis and immunoelectron microscopy is possible using this antibody. Our analyses demonstrate that creatine kinase B expression is restricted to a specific subset of cell types in various tissues. In brain, the B-subunit was found only in neurocytes, but not in glia cells. High expression was also observed in inner segments of photoreceptor cells and the outer plexiform layer of the retina, in the parietal cells of the stomach and in gut enterocytes, gallbladder and epithelial cells of the urogenital system. The possible roles of the creatine kinase/phosphocreatine-ATP system in these tissues are discussed.
Amino Acid Sequence↗
On the effect of garlic on plasma lipids and lipoproteins in mild hypercholesterolaemia.
The ingestion of garlic has been reported to have many cardiovascular effects, including a reduction in plasma cholesterol concentration and the susceptibility of LDL to oxidation. A double-blind, placebo-controlled, randomised crossover study was conducted in subjects with mild to moderate hypercholesterolaemia who were subject to strict dietary supervision and assessment. After a baseline dietary period of 28 days, subjects took Kwai garlic powder tablets 300 mg three times daily or matching placebo for 12 weeks, followed by 28 days washout, followed by a 12 weeks crossover on the alternative preparation. In the analysis hypercholesterolaemia was defined as those subjects in the range 5.5-8.05 mmol/l. Three subjects were withdrawn, one allocated to garlic and complaining of garlic body odour, one using placebo having intercurrent health problems, and one with a baseline cholesterol below 5.5 mmol/l, yielding analysable results in 28 subjects. Comparing the period on garlic with that on placebo, there were no significant differences in plasma cholesterol, LDL cholesterol, HDL cholesterol, plasma triglycerides, lipoprotein(a) concentrations, or blood pressure. Mean LDL cholesterol concentration was 4.64 +/- 0.52 mmol/l on garlic and 4.60 +/- 0.59 mmol/l on placebo. There was no demonstrable effect of garlic on oxidisability of LDL, on the ratio of plasma lathosterol/cholesterol (a measure of cholesterol synthesis), nor on LDL receptor expression in lymphocytes. This study found no demonstrable effect of garlic ingestion on lipids and lipoproteins.
Administration, Oral↗
The chemotherapy of rodent malaria. LII. Response of Plasmodium yoelii ssp. NS to mefloquine and its enantiomers.
A comparison was made between the blood schizontocidal action in mice of racemic mefloquine hydrochloride and the free bases of its (+)- and (-)-enantiomers (Ro 13-7224 and Ro 13-7225) against chloroquine-resistant Plasmodium yoelii ssp. NS. The racemic hydrochloride was two to three times as active against this parasite in mice as either of the enantiomer free bases, which were of similar activity to each other. Under drug selection pressure, the parasites acquired resistance in approximately the same time for each of the three compounds.
Animals↗
Mouse ubiquitous mitochondrial creatine kinase: gene organization and consequences from inactivation in mouse embryonic stem cells.
Individual members of the creatine kinase isoenzyme family (CK; EC 2.7.3.2), which play a prominent role in energy homeostasis, are encoded by four separate nuclear genes. We have isolated and characterized the complete mouse UbCKmit gene, the product of which is ubiquitously expressed and is located in the intermembrane space of mitochondria. Transcription of this gene is initiated at multiple adjacent positions and the region immediately upstream of these sites shares many features with genes encoding housekeeping proteins. These include a high G/C content, absence of TATA and CCAAT motifs, and presence of SP1 and AP2 recognition sequences. In addition, a binding site for HIP1, hormone-responsive elements, and three Mt-motifs, known as boxes shared between nuclear genes encoding mitochondrial proteins, were identified. To study the functional role of the UbCKmit protein, we have inactivated both UbCKmit alleles in mouse embryonic stem (ES) cells. UbCKmit-deficient cells, obtained by consecutive rounds of gene targeting using homologous recombination and drug selection-driven gene conversion events, show no obvious growth disadvantage or abnormal differentiation potential. Activities of mitochondrial cytochrome c oxidase and citrate synthase, as well as the rate of pyruvate oxidation, showed values equal to wild-type cells, indicating a normal aerobic metabolism. Mitochondria of in vivo differentiated knock-out cells were structurally intact, as demonstrated by electron microscopy. Approaches to study the role of the UbCKmit gene further are discussed.
Animals↗
A phase II trial of zeniplatin in metastatic melanoma.
A third-generation platinum analogue, zeniplatin, was administered at a dose of 145 mg/m2 intravenously over 60-90 minutes every 21 days as the initial chemotherapy to 21 patients with metastatic melanoma. Prehydration and mannitol diuresis was introduced after the first 7 patients. There were 17 males and 4 females. The median age was 52 (range: 29-81). ECOG performance status was 0 in 10 patients, 1 in 8 patients and 2 in 3 patients. Major disease sites were lymph nodes, skin, lung, liver, and bone. Patients received a median of 2 cycles (range: 1-7). Two patients achieved partial responses. One with nodal disease progressed after 166 days and the other with buccal mucosal disease after 142 days. A third patient showed partial regression of nodal disease but developed cerebral metastases. Gastrointestinal toxicity included WHO grade 3 vomiting in 8 patients and nausea in 2. Antiemetics were used, but ondansetron was not available. WHO grade 3 hematologic toxicities included neutropenia in 8 patients and anemia and thrombocytopenia in 1 patient. Thrombocytosis was seen in 35% of courses. Dosage reduction was required in 15% of courses and escalation in 5% of courses. Three patients developed phlebitis related to the infusion. One patient developed a reversible rise in serum creatinine, but, unlike other studies, no severe nephrotoxicity was reported. Zeniplatin demonstrated only modest activity in melanoma with significant gastrointestinal and hematologic toxicity.
Adult↗
Calcification of breast implant capsules: incidence, diagnosis, and contributing factors.
From January 1990 to August 1994, more than 6000 patients with silicone-gel breast implants were clinically assessed regarding their implant status. Of these, 82 patients requested removal of their implants (150 implants). Of the 150 implants that were removed, 24 (16%) demonstrated calcified capsules. All 12 patients with calcification demonstrated this finding bilaterally. All calcified capsules demonstrated discrete calcified plaques on their inner surface. All 12 patients presented with Baker class IV contractures, with pain as their chief complaint. One patient demonstrated calcification on a routine chest radiograph. One patient demonstrated a stippled appearance on xeromammogram. Capsular calcification was related to the duration of implantation. All 6 implants that had been in place for 23 to 26 years were associated with calcification. These implants were all of the thick-walled Dacron-backed type. All thick-walled Dacron-backed implants that were removed in this study were associated with calcification. Of the 69 implants that had been inserted for 11 to 20 years, 18 (26.1%) were associated with calcification. Fifteen of these 16 implants were ruptured. None of the implants that had been in place for 10 years or less demonstrated calcification.
Breast Implants↗
Silicone breast implants and autoimmune connective tissue disease.
There is currently no proven cause-and-effect relationship between breast implants and autoimmune connective tissue disease. However, there is a growing concern that immunological sensitization to silicone could potentially develop in certain susceptible patients and that this could contribute to the development of autoimmune connective tissue disease. In this article I review the current status of this potential relationship. The following areas are discussed: chemistry of silicone, potential mechanisms for an immune response, implant failure, epidemiological and antibody studies of autoimmune connective tissue disease, and recent information on certain neurological findings in a group of patients with breast implants. Current large-scale epidemiological studies should help to define any potential relationship between breast implants and autoimmune connective tissue disease.
Autoimmune Diseases↗
Do patients with silicone-gel breast implants have elevated levels of blood silicon compared with control patients?
Whole blood silicon levels in 30 patients with silicon-gel implants (inserted between 1973 and 1991) were compared with those of 24 healthy, age-matched, female patients without breast implants using atomic absorption spectrometry with a graphite furnace. The blood silicon levels in the implant patients were significantly higher than those of controls (medians 33.45 vs 17.05 ng/ml; p = 0.005). Of the 30 patients with implants, 15 had received their implants between 1973 and 1985, and 15 had received implants between 1986 and 1991. Implants made between 1973 and 1985 have been shown to be weaker and to have higher silicone "bleed" levels than those made from 1986 onward. However, there were no significant differences in the blood silicone levels between these two groups of patients.
Breast Implants↗
Analysis of silicon levels in capsules of gel and saline breast implants and of penile prostheses.
Although a potential link between silicone-gel breast implants and autoimmune connective tissue disease has been suggested, none has been proven. The potential role of silicone as an immune adjuvant remains very controversial. Currently available techniques do not allow precise measurements of silicone in tissues. However, all compounds containing silicon (including silicone) can be measured accurately. The present study was designed to measure silicon levels in the fibrous capsules of patients with silicone-gel breast implants, saline breast implants, and silicone inflatable penile prostheses. Baseline control silicon levels were obtained from the breast tissue of patients undergoing breast reduction, who had no exposure to breast implants. All silicon measurements were carried out using atomic absorption spectrometry with a graphite furnace. Silicon was measured in a normal heptane extract of silicone from dried tissue. The mean silicon levels in 16 breast tissue control samples from 8 patients undergoing breast reduction varied from 0.025 to 0.742 micrograms/gm with the median mean being 0.0927. The median silicon level in capsules from six patients with saline implants was 7.7 micrograms/gm (range, 1.9-36.6 micrograms/gm). The median silicon level in capsules from five patients with silicone inflatable penile prostheses was 19.5 micrograms/gm (range, 1.9-34.8 micrograms/gm). Although the levels of silicon in capsules of patients with saline breast prostheses and penile implants were higher than in control samples, they were much lower than those from the capsules of the 58 gel implants (median, 9,979 micrograms/gm; range, 371-152,000 micrograms/gm).(ABSTRACT TRUNCATED AT 250 WORDS)
Breast↗
Silicone gel as an adjuvant.
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Adjuvants, Immunologic↗
Full-thickness facial chemical burn from a "50% TCA" peel.
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Burns, Chemical↗