Informing patients about serious side effects of drugs. A 2001 survey of 341 French rheumatologists

OBJECTIVES: In May 2001, we surveyed French rheumatologists to determine how they inform their patients about serious side effects of drugs. RESULTS: Of the 600 rheumatologists invited to participate in the study, 341 completed and returned the questionnaire. Most respondents believed that full information on patients would become the rule (mean, 62.1 +/- 28.3, the items being scored on a 100-point scale where 0 was "not at all" and 100 "absolutely"). The answer to this item varied little across age groups. Respondents felt that patient information fell primarily on the physician, (78 +/- 23), followed by pharmaceutical companies (64 +/- 32) and pharmacists (46 +/- 33). The respondents believed that full information of patients about side effects would primarily benefit physicians (51 +/- 32), followed by pharmaceutical companies (43 +/- 30) and patients (38 +/- 28). The reaction of patients to information on drug-related risks was described as "always favorable" by 2% of the respondents and as "fairly often favorable" by 55%. Among respondents, 9% always gave information on serious side effects, 66% fairly often, and 4% never; 2% always communicated information on the approximate frequency of serious adverse events, 21% fairly often, and 33% never. Similarly, 3% of the respondents always warned their patients of lethal risks, 11% fairly often, and 44% never. When evaluated on a 100-point scale (0, not at all knowledgeable; 100, very knowledgeable), knowledge of serious side effects of drugs for musculoskeletal conditions was 73 +/- 23, whereas knowledge of the frequency of these effects was only 52 +/- 22. Eight percent of the respondents always recommended that patients read the package insert, 27% fairly often, and 32% never. Conversely, the possible adverse effects of not taking the treatment were always specified by 21% of the respondents and fairly often by 88%.     

Treatment of Old World cutaneous leishmaniasis by pentamidine isethionate. An open study of 11 patients

BACKGROUND: Pentavalent antimonial derivatives (PAD), especially meglumine antimoniate (Glucantime((R))), are usually considered as the first-line drugs for Old World leishmaniasis, but their potential toxicity and the number of required injection, either intralesional or intramuscular, prompt to search for alternative treatments. OBJECTIVE: To evaluate the efficiency and tolerance of pentamidine isethionate in Old World leishmaniasis. METHODS: An open pilot study included 11 patients from two regional academic centers, with varied parasitological forms of Old World leishmaniasis, treated with three strictly intramuscular injections of 4 mg/kg of base-pentamidine every other day. RESULTS: Tolerance was good overall, and 8/11 (73%) of patients responded well with a quick healing of their lesions, little scarring and no relapse. CONCLUSION: Pentamidine isethionate is a safe and effective first-line treatment for Old World leishmaniasis. Larger-scale prospective studies comparing several dosage regimens of pentamidine and pentamidine isethionate to PAD are warranted.     

Cytoprotection and iron mobilization in rat hepatocyte cultures by a new synthetic dihydroxamate chelator

The cytoprotection and iron mobilization effect of a new dihydroxamate chelator 1,1 bis [(11-N-hydroxy)-2,5,11-triaza-1,6,10-trioxo dodecanyl] ethane or KD was studied in primary rat hepatocyte cultures exposed to iron-citrate. Lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production were measured as indexes of cytotoxicity. Cell viability was evaluated using the [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide] (MTT) reduction test. To demonstrate that this chelator was able to decrease iron uptake or increase iron release from the hepatocytes, labelled cells were obtained by maintaining the cultures in the presence of 0.02 microM 55Fe-citrate. The efficacy of KD was compared to desferrioxamine B (DFO) at stoechiometry concentrations. After 24 h of exposure to 50 microM of iron-citrate, a significant release of LDH and MDA was observed. Cell viability was also significantly decreased. When 100 microM of KD were added at the same time as iron, LDH and MDA release was decreased and cell viability was improved. In the presence of the same chelator concentration, a net decrease of iron uptake by the cells was observed as attested by the low intracellular 55Fe level. Moreover, in the 55Fe loaded hepatocytes, the chelator increased the iron extracellular level indicating its iron release effect from the cells. In all tested experimental conditions, the efficacy of 100 microM of the dihydroxamate chelator KD was close to that of 50 microM of the trihydroxamate chelator DFO. In conclusion, KD is effective at a level comparable to DFO in protecting rat hepatocytes against the toxic effect of iron-citrate by decreasing the uptake of the metal and increasing its release from the cells. This synthetic compound appears to have some potential therapeutical interest and the results obtained encourage the synthesis of new hydroxamate ligands.     

Delays in diagnosis and melanoma prognosis (II): the role of doctors

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.     

Genetic susceptibility associated with rare HRAS1 variable number of tandem repeats alleles in Spanish non-small cell lung cancer patients.

The highly polymorphic HRAS1 variable number of tandem repeats (VNTR), which maps 1 kb downstream from the human H-ras1 gene, has been described as an inherited predisposing factor in many human cancers. Here, we investigated the association between the presence of rare HRAS1 minisatellite alleles and lung cancer in the population studied. Four hundred sixty-six HRAS1 VNTR alleles from 233 lung cancer patients and 892 alleles from 446 unaffected controls were typed using PCR-long agarose gel electrophoresis assay of peripheral blood lymphocyte DNA. Rare alleles were differentiated from common alleles (a1, a2, a3, and a4) by shifts in electrophoretic mobility. Odds ratio was calculated to evaluate increased risk of lung cancer associated to the presence of rare HRAS1 alleles. A higher percentage of rare HRAS1 VNTR alleles in lung cancer patients than in unaffected controls (32.7 versus 21.9%) was confirmed. The presence of rare alleles was associated with an increased risk of lung cancer (odds ratio = 1.68; P < or = 0.0001), indicating a genetic predisposition to lung cancer. No differences based on other clinicopathological variables were observed. Furthermore, a meta-analysis showed a higher distribution of rare alleles in our study of Caucasian Spaniards than was found in other studies of American and Northern European Caucasian populations. We conclude that the presence of rare HRAS1 VNTR alleles may be an inherited predisposing factor in lung cancer. This presence can be easily determined from peripheral blood samples by PCR-based methods. Furthermore, interracial variations in allele frequencies and variations between Caucasian subpopulations suggest that genetic variations may be involved in susceptibility to lung oncogenesis, especially in certain ethnic populations.     

Application of the pulsed light technology to mycotoxin degradation and inactivation

The persistence of mycotoxins and their metabolites in agricultural products is a major safety concern because of their high resistance to all kinds of decontamination techniques. In this study, we evaluated the effectiveness of the pulsed light technology for the degradation of mycotoxins. We report that eight flashes of pulsed light destroyed of 84.5 ± 1.9, 72.5 ± 1.1, 92.7 ± 0.8 and 98.1 ± 0.2% of zearalenone, deoxynivalenol, aflatoxin B1 and ochratoxin in solution. The degradation of the molecules was monitored by HPLC and LC‐MS/MS analysis. We estimated the potential toxicity of zearalenone and deoxynivelenol after exposure to a pulsed light treatment using the Caenorhabditis elegans survival tests. The genotoxicity of aflatoxin B1 was also investigated using a complete Ames test. The results show that the treatment of zearalenone and deoxynivelenol by single or multiple flashes of pulsed light is associated with a stagnation or marginal decrease of the toxicity of the mycotoxins and that treatment of aflatoxin B1 by pulsed light can completely eliminate the mutagenic potential of this mycotoxin. This work provides the first demonstration of a nonthermal technology allowing mycotoxin destruction and inactivation of their mutagenic activity. Copyright © 2011 John Wiley & Sons, Ltd.     

Comparison of histomorphometric and radiographic effects of growth guidance with tension-band devices (eight-Plate and FlexTack) in a pig model

Background and purpose — Temporary hemiepiphysiodesis for growth modulation in skeletally immature patients is a long-known technique. Recently the use of tension-band devices has become popular. This study compares 2 tension-band implants (eight-Plate and FlexTack) regarding their effects on the growth plate.Animals and methods — 12 pigs in 2 equally sized groups (A and B) were investigated. The right proximal medial tibia was treated with either eight-Plate or FlexTack. The left tibia of the same pig was treated with the opposite implant. After 9 weeks all implants were removed. Animals in group B were then hosted for another 5 weeks. Histomorphometric analysis of the growth plate was carried out after 9 and 14 weeks, respectively. Radiographs were taken at implantation, removal, and after 14 weeks.Results — Both tension-band devices achieved a statistically significant and clinically relevant growth inhibition, whereas the effect appeared to be more distinct after the use of FlexTack. Implant-related complications or physeal damage was not observed. After implant removal, rebound phenomenon was radiologically observed in all cases. The growth plates treated with eight-Plate showed a paradox reversal of the zonal distributions, with an increase of the proliferative zones at the previously arrested medial aspect of the physis and a decrease laterally.Interpretation — Both eight-Plate and FlexTack proved to be appropriate devices for growth-guiding treatment. The radiographic evaluation showed a change in angular axes after treatment with each implant, while the correction appeared to be faster with FlexTack. The paradox cartilaginous reaction observed after removal of the eight-Plate might be a histopathological correlate for rebound phenomenon.

To achieve realignment of angular deformities in skeletally immature patients, remaining bone growth can be used for growth modulation procedures to avoid extensive surgical interventions (Stevens 2007). Temporary hemiepiphysiodesis (THE) aims to mechanically inhibit growth on one side of the physis through a bridging implant. The procedure has to be performed before skeletal maturity, to maintain sufficient potential for correction while also reducing the risk of relapse of the deformity after implant removal (rebound phenomenon). Blount in 1949 described a stapling technique for THE, which provided good results in the correction of angular deformities but was later linked to complications like implant failure and physeal damage (Blount and Clarke 1949, Kanellopoulos et al. 2011, Stevens 2007). In 2007 Stevens introduced a non-locking 2-hole plate (eight-Plate [EP], Orthofix Medical Inc, Lewisville, TX, USA) based on the tension-band principle (Stevens 2007). Even though treatment with the EP seems to have an overall decreased complication rate, screw breakage is still reported rather frequently (Schroerlucke et al. 2009, Burghardt et al. 2010, 2011, Scott 2012, Vogt et al. 2016). This led to the development of a flexible staple (FlexTack [FT], Merete GmbH, Berlin, Germany). Both implants, EP and FT, achieve a tension-band effect through an extra-physeally located fulcrum of correction supposedly leading to reduced compression on the physis, thus decreasing the risk of premature closure of the physis (Vogt et al. 2016). Different from the EP, the FT is a 1-piece implant with a flexible mid-zone that provides dynamic bending under bone growth force.We examined the physeal response to THE with these 2 tension-band devices and whether there is a histomorphological correlate for the extent of the blockage between FT and EP. Additionally, we sought a possible histomorphological explanation for the excessive unilateral bone growth frequently occurring after implant removal, which might be linked to the incidence of rebound phenomenon.     

Anatomic and physiologic comments concerning the innervation and function of the omohyoid muscle in man

Electrophysiological studies of the rather strange, enigmatic, likely vestigial omohyoid muscle led the authors to point out the dual nature of its two bellies. Electromyographically, the inferior belly with a nearly constant activity may be opposed to the superior belly with intermittent activity. Motor nerve stimulation combined with electromyographic study demonstrated the superior belly to be supplied by the ansa cervicalis while the inferior belly is supplied by the accessory nerve. Based on these findings, anatomical studies conducted with histological examination were consistent with this double innervation.