Rupture of silicone-gel breast implants.
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Breast Implants↗
Biomedical subjects
W Peters
Publications and source records attributed to W Peters.
Drug resistance in malaria parasites of animals and man.
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Animals↗
Glutathione homeostasis is disturbed in CD4-positive lymphocytes of HIV-seropositive individuals.
BACKGROUND: Numerous in vitro tests have suggested that a disturbed cellular glutathione homeostasis plays an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. METHODS: Using validated high-performance liquid chromatography (HPLC) methods, glutathione concentrations were determined in plasma and in cytosol of CD4+ lymphocytes and CD14+ cells of HIV-seropositive individuals and healthy control subjects. We measured concentrations of total glutathione, which is the sum of reduced (GSH) and oxidised (GSSG) glutathione and mixed disulphides of which there are two fractions: soluble mixed disulphides (GSSR) and protein bound glutathione (ProSSG). Also, non-protein-bound glutathione was measured, which is the sum of GSH, GSSG and GSSR. Thirty-five healthy control subjects and 35 HIV-infected individuals participated in the study. RESULTS: We found that in CD4+ lymphocytes from HIV-seropositive individuals, total glutathione levels were significantly higher than in healthy control subjects, whereas the fraction of non-protein-bound glutathione was not different. This can only be explained by an increase in the protein-bound fraction of glutathione indicating the presence of oxidative stress in CD4+ lymphocytes of HIV-seropositive individuals. Glutathione measurements of cytosol of CD14+ cells and plasma were, however, not compatible with significant increased oxidation. Glutathione precursors (cysteine, cysteinylglycine, glutamylcysteine and homocysteine) and products of lipid peroxidation (thiobarbituric acid-reactive substances) were also measured in plasma and did not differ between healthy control subjects and HIV-seropositive individuals. CONCLUSION: We conclude that the glutathione homeostasis is disturbed in CD4+ lymphocytes of HIV-seropositive individuals. The glutathione redox dysbalance in CD4+ lymphocytes could be important in the pathogenesis of HIV infection and have implications for therapy.
Adult↗
Capsular calcification associated with silicone breast implants: incidence, determinants, and characterization.
Capsular calcification was present clinically in 64 of 404 silicone gel breast implant capsules (15.8%) analyzed from 1981 to 1996. It presented as white-gray plaques on the inner surface of capsules in 62 of 64 capsules, and as massive heterotopic ossification in 2 capsules. Chi-squared analysis confirmed that calcification was related to the generation of the implant (i.e., year of manufacture; p < 0.001). All 28 first-generation implants (1963-1972, with Dacron patches) were clinically intact and all demonstrated extensive calcification. Their mean duration in situ was 17.6 years (range, 14-28 years). Thirty-four of the 348 second-generation implants (9.8%; 1973-1987) were associated with capsular calcification. Their mean duration in situ was 16.0 years (range, 13-22 years). Because all first-generation implants demonstrated calcification, they were compared with the second-generation implants that had been in place for the same duration (>14 years). Only 42% of these 81 second-generation implants demonstrated calcification, compared with 100% of the first-generation implants (p < 0.001). Thus, thicker first-generation implants with Dacron patches are more likely to calcify and the effect is not entirely due to their longevity. None of the 28 third-generation implants (1987-1991) demonstrated calcification. Their mean duration in situ was 4.2 years (range, 2-7 years). For second-generation implants, calcification was related to duration in situ (p < 0.001). None of the 294 implants in place for less than 11 years were associated with significant clinical calcification. The percentages of capsules with calcification were 13 to 14 years, 33%; 15 to 16 years, 45%; and 17 to 22 years, 57%. Calcification with second-generation implants was not associated with patches on the envelopes. Of the 34 second-generation implants with calcification, only two had patches (composed of silicone, not Dacron). Among second-generation implants, calcification was related to implant integrity. Of implants in place for more than 12 years, 52.5% of those implants that were ruptured showed calcification, but only 10.0% of intact implants demonstrated calcification (p < 0.001). Seventeen of the 64 calcified capsules were examined histologically. In all of these specimens, calcification existed in two forms: globular aggregates on the surface of the capsule (adjacent to the implant) and actual bone formation within the fibrous tissue of the capsule. All calcified capsules demonstrated both globular aggregates and true bone formation regardless of the implant generation, duration in situ, or integrity. Ultrastructural analysis was performed on four capsules from 2 women who had received first-generation Dow Corning gel implants 24 and 28 years previously, and on 2 capsules from one woman who had received Heyer-Schulte gel implants 21 years previously. These capsules were analyzed according to distribution, density, mineral nature, crystal phases, and elements within crystals by electron microscopy, energy-dispersive X-ray spectrometry, and electron diffraction. These analyses confirmed two types of calcification, each with hydroxyapatite crystals. In areas of heterotopic bone, crystals 40 x 10 nm were deposited in an orderly fashion on collagen fibers. In contrast, in areas of globular aggregates, spherulitic aggregates of much larger crystals were present, without any relationship to the collagen. Titanium was demonstrated in capsules of first-generation implants at areas of attachment of the Dacron patches. The calcification associated with saline implants revealed only one form of crystal: agglomerates, which were adherent to the elastomeric shell of the implants. A hypothesis is presented to explain the differences in calcification deposition properties between silicone gel-filled and saline-filled breast implants.
Adult↗
Determining the frequency of breast implant failure requires sound scientific principles.
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Bias↗
Preserved autonomic modulation of the sinus and atrioventricular nodes following posteroseptal ablation for treatment of atrioventricular nodal reentrant tachycardia.
INTRODUCTION: Following radiofrequency catheter ablation of AV nodal reentrant tachycardia (AVNRT), inappropriate sinus tachycardia may occur, possibly due to damage to autonomic cardiac nerve fibers. Furthermore, inducibility of AVNRT is often critically dependent on the autonomic balance. We investigated whether successful ablation of AVNRT is associated with an alteration of autonomic input to the sinus and AV nodes. METHODS AND RESULTS: To estimate changes in the autonomic modulation of the sinus and AV nodes, power spectra of beat-to-beat PP and PR intervals were analyzed from high-quality nighttime ECG recordings of 11 patients before and after radiofrequency application. Normalized HF power (nHF) of PP and PR intervals was used as an index of efferent vagal modulation and the LF/HF ratio as an index of sympathovagal balance of the sinus node (PP) and AV node (PR). Before ablation, LF/HF(PP) was 3.2 and nHF(PP) was 0.3 in the sinus node. For the AV node, LF/HF(PR) was 1.2 and nHF(PR) was 0.5. Following ablation, LF/HF(PP) (3.5) and nHF(PP) (0.3) of the PP intervals did not change. Similarly to the sinus node, there were no changes in the autonomic modulation of the AV node, as both LF/HF(PR) (1.2) and nHF(PR) (0.5) remained unchanged. CONCLUSION: Our results indicate that autonomic control of the sinus and AV nodes is preserved following successful radiofrequency ablation of AVNRT. The effects of posteroseptal radiofrequency current application are not necessarily mediated by changes in the autonomic input to the AV node.
Adult↗
Body surface potentials during discharge of the implantable cardioverter defibrillator.
INTRODUCTION: Little is known about the hazard for persons in contact with patients experiencing a high-voltage discharge of their implantable cardioverter defibrillator (ICD). Compared to epicardial systems, this risk may be increased with transvenous electrode systems and particularly in active can configurations. METHODS AND RESULTS: In 23 patients with a transvenous active can ICD system, body surface potentials Vs and current through an external resistance were measured during 35 discharges. Vs was detected using skin electrodes positioned over the left subpectorally implanted pulse generator [C], apex of the heart [A], and the right pectoral region [RP]. Mean Vs during discharges without an external shunt resistance ranged between 13 and 63.8 V [C to A] and 12.5 to 47.3 V [C to RP] (ICD peak stored/output voltage Vcap = 183 to 606 V, n = 20). Mean current flow [C to A] was 8.2 to 46.8 mA (Vcap = 288 to 633 V, n = 10) and 42 to 120.7 mA (Vcap = 447 to 579 V, n = 5) across a resistance of 1,696 and 797 omega, respectively. CONCLUSION: During high-output shocks, a considerable potential difference is present on the body surface of ICD patients that, according to the literature, may induce a single cardiac response in a bystander. Analogous to spontaneous extrasystoles, there is only a minimal chance of triggering a tachyarrhythmia by this stimulated extra beat. Direct induction of ventricular fibrillation is unlikely, since reported fibrillation threshold values are much higher than the observed magnitudes of current and voltage.
Aged↗
Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy.
BACKGROUND: In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS: Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS: The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.
Adenosine Triphosphate↗
Marker for liver damage in neonates born to mothers with HELLP syndrome.
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Biomarkers↗
[Implantation of a transvenous defibrillation system in isolated persistent left superior vena cava].
HISTORY AND CLINICAL FINDINGS: A 49-year-old man, an alcoholic for the past 7 years, complained of dizziness, palpitations and exertional dyspnoea (NYHA stage III). Physical examination revealed peripheral cyanosis, slightly raised jugular venous pressure, râles in the lung bases, a loud systolic murmur, maximal over the apex, and an enlarged palpable liver. INVESTIGATIONS: Results of biochemical tests were unremarkable. The ECG showed sinus rhythm, 1 degree AV block and signs of left ventricular hypertrophy. Chest radiogram demonstrated cardiac dilatation and probably absent right superior vena cava (SVC). Long-term ECG monitoring during episodes of dizziness and one syncope revealed self-limited periods of unifocal ventricular tachycardia. Echocardiography and angiography showed bilateral ventricular dilatation with an ejection fraction reduced to 20%, as well as mild mitral and moderate tricuspid regurgitation but normal cardiac valves, suggesting a dilated cardiomyopathy. Coronary angiography was normal. No myocarditis was revealed on myocardial biopsy. The patient declined electrophysiological investigation. TREATMENT AND COURSE: Amiodarone caused higher degree AV block. A temporary pacemaker lead was inserted via the persistent left SVC, amiodarone discontinued and later a pacemaker-defibrillator system (ICD) implanted, previous digital subtraction angiography having demonstrated a left SVC and absent right SVC. The transvenous electrode had been placed via the left subclavian vein, left SVC (anode), coronary sinus, right atrium into the right ventricle (cathode), and the pacemaker-defibrillator implanted subpectorally. Stable electrode position and correct ICD function has been documented over 2 years. 4 months after implantation bursts of ventricular tachycardia recurred every few minutes that responded to renewed amiodarone administration. CONCLUSION: Good long-term results can be obtained with ICD electrodes implanted via a persistent LSVC.
Amiodarone↗
Modifications in the rhythm of schizogony in Plasmodium chabaudi chabaudi associated with the selection of chloroquine resistance.
A high level of drug resistance was obtained with a line of Plasmodium chabaudi maintained under intense chloroquine selection pressure according to the protocols established for P. berghei. The main objective of this work was to verify if the characteristic asynchronous schizogonic rhythm of naturally resistant rodent malaria parasites was also found when the drug resistance was induced experimentally. The degree of resistance was evaluated through the use of the "2% delay test" (DT) and the schizogonic rhythm, by reference to the synchronicity index (SI). The strain had originally a DT of 4.26 and an SI of 0.52. Following the application of 80 mg/kg chloroquine at each passage, as early as at the 8th passage the parasites rapidly became resistant and asynchronous. At the 17th passage the DT was 3.32 and the SI, 0.20. In the drug-resistant line the original indices, both the DT and the SI, were restored after deep-freezing, sporogony, or passage through a Percoll gradient, or simply by repeated intravenous subinoculations of blood. The clear correlation between asynchronicity and drug resistance is easily explained by the action of chloroquine, which favours the schizogonic cycles initiated by latent merozoites.
Animals↗
The chemotherapy of rodent malaria. LIII. 'Fenozan B07' (Fenozan-50F), a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane: comparison with some compounds of the artemisinin series.
Fenozan B07, a difluorinated 3,3'-spirocyclopentane, 1,2,4-trioxane, is a novel, second-generation antimalarial endoperoxide which is a potent blood schizontocide against strains of rodent malaria that are highly resistant to a wide spectrum of classical antimalarials. Like compounds of the artemisinin series, its action is limited to the intra-erythrocytic stages, both asexual and sexual, and it is devoid of causal prophylactic activity. Both Fenozan B07 and the artemisinins are potent gametocytocides. In contrast to arteether, in a model using synchronous infection with Plasmodium vinckei petteri, Fenozan B07 inhibits the development of all asexual stages except preschizonts, as well as gametocytes. The activity of the artemisinin series in rodent-malaria models is limited to the rings and young trophozoites. The combined effect of Fenozan B07 with artesunate against P. v. petteri was only additive. A slight degree of potentiation was found in mice infected with asynchronous, drug-sensitive P. berghei but the combination was only additive against CQ-resistant P. yoelli ssp. NS. On the other hand, a significant degree of synergism was observed when mice infected with the artemisinin-resistant ART line of P. yoelii ssp. NS received combinations of Fenozan B07 with artemisinin. The conclusion is drawn from these and other data that there are significant differences between the blood schizontocidal actions of Fenozan B07 and the artemisinins. The basis of these differences remains to be determined.
Animals↗
The chemotherapy of rodent malaria. LIV. Combinations of 'Fenozan B07' (Fenozan-50F), a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane, with other drugs against drug-sensitive and drug-resistant parasites.
Fenozan B07, a 1,2,4-trioxane endoperoxide with potent blood schizontocidal activity against drug-sensitive and drug-resistant rodent malaria parasites, exerted a modest potentiating action when administered with chloroquine (CQ) to mice infected with parasites of the CQ-resistant P. yoelii ssp. NS, but not when given to mice infected with the CQ-sensitive P. berghei N strain. The reason why this potentiation may be of particular value in the treatment of severe falciparum malaria is discussed. Mefloquine and halofantrine displayed a similar level of potentiation with Fenozan B07 against the CQ-resistant parasites. However, antagonism was shown by combinations of Fenozan B07 with pyronaridine or the 8-aminoquinoline WR 238 605 when used against CQ-resistant parasites. Mefloquine with Fenozan B07 is also antagonistic against a highly mefloquine-resistant line of P. yoelii ssp. NS. The reasons behind such antagonism are not known. The importance is stressed of using carefully selected drug combinations of novel antimalarials, rather than single drugs, in order to impede the selection of drug-resistant parasites, but only after adequate, preclinical, toxicity testing.
Aminoquinolines↗
The chemotherapy of rodent malaria. LV. Interactions between pyronaridine and artemisinin.
Two interactions of two potent blood schizontocides, pyronaridine and artemisinin, were assessed in mice infected with chloroquine-resistant Plasmodium yoelii ssp. NS or one of two lines derived from it, namely ART, which is resistant to artemisinin and SPN, which is resistant to pyronaridine. While the drug combination proved to be only additive in its action against P. yoelii ssp. NS, a marked potentiation between the two compounds was observed against the ART and SPN lines. The implications of the findings in terms of the impeding of drug resistance when these compounds are deployed for the treatment of multi-drug-resistant P. falciparum are discussed.
Animals↗
An outcome analysis of 100 women after explantation of silicone gel breast implants.
A prospective outcome analysis was conducted on 100 consecutive women who requested explantation of their silicone gel breast implants from January 6, 1992 (the moratorium), through 1995. Eighteen patients were referred by rheumatologists with a diagnosis of autoimmune or rheumatic disease. Six had autoimmune disease (systemic lupus, 2 patients; rheumatoid arthritis, 2 patients; multiple sclerosis, 1 patient; and Raynaud's disease, 1 patient). Twelve had rheumatic disease (fibromyalgia, 10 patients; inflammatory arthritis, 2 patients). All of these 18 patients had developed symptoms of their disease after they had received implants. All 100 patients were extensively evaluated pre- and postoperatively by interviews, clinical assessment, and by assay of the following laboratory tests: rheumatoid factor, ESR, ANA, and anti-Ro/SSA, -La/SSP, -Sm, -RNP, -double-stranded deoxyribonucleic acid, -Scl-70, -centromere, and -cardiolipin. Patients were also evaluated by a questionnaire that was sent at a mean time of 2.7 years postexplantation (range, 1-5 years), which had a 75% response rate. Reasons for implants were augmentation, 75%; lifting, 11%; reconstruction, 12%; and congenital aplasia, 2%. The mean age at first implant was 28.9 years (range, 13-55 years) and at explantation was 41.5 years (range, 25-65 years). The mean duration of implantation was 12.0 years (range, 1-27 years). Thirty-six percent of the patients had undergone at least one closed capsulotomy and 54% at least one open capsulotomy. The mean reasons for explantation were suspected silicone-related health problems, 76%; suspected rupture, 59%; breast firmness, 36%; breast pain, 36%; and musculoskeletal pain, 23%. Before explantation 75% of the questionnaire respondees had lost some sensitivity in their nipples following their breast augmentation. In 36% of those 75 patients, that loss was almost complete. Loss of sensitivity was related to capsular contracture and to pain (p < 0.05). Following explantation there was significant improvement in nipple sensitivity in 38% of breasts in the 75 respondees. A total of 186 implants were removed. Fifty-seven percent had failed by rupturing or leaking. Only 3.2% demonstrated extravasation extracapsularly. Twenty-five percent of the capsules were calcified, demonstrating visible plaques of calcification on their inner surface. Forty-two percent were colonized by bacteria. The prevalence of class III-IV capsular contracture was 61% and it was related to implant location, duration in situ, and capsular calcification (p < 0.05), but not to capsular colonization or implant integrity (p > 0.05). Only 43 of the 100 patients elected to have saline implants inserted. Of the others, 56% felt that the shell of the saline implant could be associated with medical problems. The others felt that breast size was of minor importance to them at this time. There were few complications from the explantation procedure. Two "masses" were discovered-one was an occult carcinoma, the other a galactocele. There was one wound infection, which responded to antibiotics. Three patients developed decreased sensitivity and 3 developed increased breast pain. From the patient questionnaires, in those women who did not have saline implants inserted, 15% felt that their breast appearance was improved after explantation, 36% were "pleased," 33% were disappointed, and 13% felt "mutilated". In women who did have saline implants inserted, 18% felt that their breast appearance was now improved, 60% were "pleased," and 14% were disappointed, mainly because of wrinkling. At a mean time of 2.7 years (range, 1-5 years) after explantation, 45% of the 75 questionnaire respondees felt that their implants had caused permanent health problems and 56% felt that they had not been given adequate informed consent by their original surgeon (particularly regarding implant rupture and a possible relationship to medical disease). (ABSTRACT TRUNCATED)
Adolescent↗
Inappropriate discharge of an implantable cardioverter defibrillator during atrial flutter and intermittent ventricular antibradycardia pacing.
INTRODUCTION: Inappropriate discharges of an implantable cardioverter defibrillator (ICD) are troublesome to the patient and sometimes a difficult task for the physician trying to identify and treat the cause. METHODS AND RESULTS: For the first time, we report a mechanism of inappropriate ICD discharges during episodes of atrial flutter with a slow ventricular response and intermittent antibradycardia pacing. The episodes occurred in two patients and were triggered by the unique sensing algorithm of the Ventritex Cadence V-100 in combination with the tripolar CPI Endotak 072 transvenous defibrillation lead, which provides integrated bipolar sensing. CONCLUSION: Besides treatment of the underlying arrhythmia, reprogramming of the device, an electrode position far away from the atria, and true bipolar sensing will enhance the performance of ICD systems with respect to the episodes described here. In addition, more flexible sensing algorithms may, in the future, prevent this overall rare complication.
Aged↗
Antimalarial activity of the bisquinoline trans-N1,N2-bis (7-chloroquinolin-4-yl)cyclohexane-1,2-diamine: comparison of two stereoisomers and detailed evaluation of the S,S enantiomer, Ro 47-7737.
The S,S enantiomer of the bisquinoline trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine, Ro 47-7737, is significantly more potent against chloroquine-resistant Plasmodium falciparum than the R,R enantiomer and the previously described racemate. Both the enantiomers and the racemate are more potent inhibitors of heme polymerization than chloroquine, and their activities are probably mediated by inhibition of this parasite-specific process. The S,S enantiomer, Ro 47-7737, was studied in more detail and proved to be a potent antimalarial in the treatment of P. vivax ex vivo and P. berghei in vivo. Its suppression of P. berghei growth in a mouse model (50% effective dose, 2.3 mg/kg of body weight) was equal to that of chloroquine and mefloquine, and Ro 47-7737 was found to be more potent than these two drugs in the Rane test, in which the curative effect of a single dose is monitored. The dose at which 50% of animals were permanently cured (34 mg/kg) was markedly superior to those of chloroquine (285 mg/kg) and mefloquine (> 250 mg/kg). When administered orally at 50 mg/kg, Ro 47-7737 also showed a faster clearance of parasites than either chloroquine or mefloquine, and unlike the other two compounds, Ro 47-7737 showed no recrudescence. In a study to compare prophylactic efficacies of oral doses of 50 mg/kg, Ro 47-7737 provided protection for 14 days compared to 3 days for mefloquine and 1 day for chloroquine. The good curative and prophylactic properties of the compound can be explained in part by its long terminal half-life. The ability to generate parasite resistance to Ro 47-7737 was also assessed. With a rodent model, resistance could be generated over eight passages. This rate of resistance generation is comparable to that of mefloquine, which has proved to be an effective antimalarial for many years. Toxicity liabilities, however, ruled out this compound as a candidate for drug development.
Animals↗
Assessment of health risks due to hazardous air pollutant emissions from electric utilities.
Hazardous air pollutant (HAP) emissions from electric utilities were evaluated. Cancer risks, as well as noncancer effects, due to inhalation exposure were assessed for 67 HAPs. Also, cancer risks due to multipathway exposure to radionuclide emissions were assessed. In addition, an assessment of the fate of mercury (Hg) through various environmental media was included. Results suggest arsenic, chromium, and nickel are the HAPs that present the highest cancer risk due to inhalation exposure. For noncancer effects due to inhalation exposure, hydrogen chloride appears to present the greatest potential concern. The risks due to multipathway exposure to radionuclides are estimated to be of similar magnitude to the risks posed by inhalation of arsenic and nickel. Mercury is of potential concern for multipathway exposures because it persists in the environmental and bioaccumulates in the aquatic food web. The study suggests there is a plausible link between Hg emissions from utilities and the Hg found in soil, water, and freshwater fish.
Air Pollutants↗