Growing old disgracefully: the cosmetic use of botulinum toxin

The explosive growth in the use of botulinum toxin for cosmetic purposes has undoubtedly had an impact on the number of animals used in the potency testing of this product. The test used is a classical LD50, a severe procedure during which animals experience increasing paralysis until the occurrence of death. The enthusiastic adoption by the general public of the use of botulinum toxin as an anti-wrinkle treatment has, at least in Europe, paradoxically taken place against a background of moves to stop animal testing of cosmetics and cosmetic ingredients. There appears to be a dearth of information aimed at the public concerning botulinum toxin testing. Botulinum toxin does have important medical applications; however, the question arises whether a blanket licence for the testing can be justified, when a large proportion of the product is being used cosmetically. A further question is why death continues to be the endpoint of the potency test, when a more-humane endpoint has been proposed. In addition, a number of alternative methods have been developed, which could have the potential to replace the lethal potency test altogether. These methods are discussed in this paper, and the importance of establishing a strategy for their validation is emphasised, a need that has become even more urgent in the light of the recently published draft monograph on botulinum toxin by the European Pharmacopoeia Commission.     

The use of botulinum toxin type A in aesthetic mandibular contouring

The lower third of Asian faces is wider than that of Caucasians and it is determined by the size and width of the mandibular bone and the thickness of muscles and subcutaneous fat tissues surrounding it. Efforts to create an aesthetically slim and smooth facial contour line in nonobese people have led the authors to focus on two approaches: surgical resection of the masseteric muscle and modeling ostectomy of the square-angled mandibular bone. Because these procedures present some problems, the authors adopted a nonsurgical concept that chemically denervates muscles and reduces the bulk of the muscle. The authors have conducted a total of 1021 clinical cases from March of 2001 through September of 2002, in which patients were treated with botulinum toxin type A (Dysport; Ipsen Ltd, Slough, United Kingdom) for remodeling the lower facial contour line; 383 of those cases were followed up for at least 3 months after the initial injection. A database was made by measuring the change in the thickness of the injected muscle with an ultrasonogram. Eleven patients underwent resection of the mandibular angle before injection. The preinjection ostectomy group was involved in the study as a result of their dissatisfaction with the surgical results; they had a rather thick masseter muscle and not a bone problem. Some had both bone problems and a thick masseter muscle. Three months after the botulinum toxin injection, the thickness of the muscle was reduced by 31 percent on average. The atrophic effect of injection was observed after 2 to 4 weeks for most patients. Seventy percent of the 383 patients tracked were greatly satisfied with the result, with another 23 percent generally satisfied. No long-term side effects were reported. Masseteric hypertrophy is frequent in Asians because of racial characteristics and dietary habits. Botulinum toxin type A has made a new epoch in facial contouring for Asians. Considering that Asians have a prominent malar and a prominent mandible angle, the reduction in the thickness of the masseter can provoke relative prominence of the malar and mandible angle. Therefore, precise indication and anatomy of the facial muscle should be thoroughly understood, which will decrease the incidence of side effects and problems. Botulinum toxin type A (Dysport) injection is simple in technique, has few side effects, and promises a rapid return to daily life. The authors conclude that the injection of botulinum toxin type A can replace surgical masseter resection.     

Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle

Botulinum toxin injection into the pylorus is reported to improve gastric emptying in gastroparesis. Classically, botulinum toxin inhibits ACh release from cholinergic nerves in skeletal muscle. The aim of this study was to determine the effects of botulinum toxin on pyloric smooth muscle. Guinea pig pyloric muscle strips were studied in vitro. Botulinum toxin type A was added; electric field stimulation (EFS) was performed every 30 min for 6 h. ACh (100 microM)-induced contractile responses were determined before and after 6 h. Botulinum toxin caused a concentration-dependent decrease of pyloric contractions to EFS. At a low concentration (2 U/ml), botulinum toxin decreased pyloric contractions to EFS by 43 +/- 9% without affecting ACh-induced contractions. At higher concentrations (10 U/ml), botulinum toxin decreased pyloric contraction to EFS by 75 +/- 7% and decreased ACh-induced contraction by 79 +/- 9%. In conclusion, botulinum toxin inhibits pyloric smooth muscle contractility. At a low concentration, botulinum toxin decreases EFS-induced contractile responses without affecting ACh-induced contractions suggesting inhibition of ACh release from cholinergic nerves. At higher concentrations, botulinum toxin directly inhibits smooth muscle contractility as evidenced by the decreased contractile response to ACh.     

Use of botulinum toxin

In an extensive survey of postgraduate physicians in two teaching hospitals (N = 141) for their humanistic attitudes, values and behavior, all ratings of physicians'' humanistic performance, including physicians'' own scores on self-report measures, supervising faculty, nurses and patient ratings, were modestly but significantly correlated with each other. Sex, ethnic or racial background, year of training, marital status, number of children, Alpha-Omega-Alpha membership or number of articles published were unrelated to physicians'' humanistic behavior. Several measures of humanism were positively correlated with having taken more courses in the social sciences and humanities, having had more early person-centered work experience and reporting that before medical school others had confided in them or sought their advice more frequently.     

Metabolism in pedicled and free TRAM flaps: a comparison using the microdialysis technique

The most common complication in flap surgery is of a circulatory nature. Impeded blood flow leads to altered metabolism in the tissue. Possible metabolic differences between different zones of the transverse rectus abdominis muscle (TRAM) flap were studied and the metabolism of pedicled and free TRAM flaps was compared intraoperatively and postoperatively. The method used was microdialysis, which is a useful technique for following local metabolic changes continuously in various tissues.Twenty-two patients with a pedicled or free TRAM flap were monitored using the microdialysis technique. Two microdialysis catheters were placed subcutaneously in the flap (zone I and zone II), and a third one was placed subcutaneously in the flank to serve as a control. The flaps were monitored intraoperatively and postoperatively for 3 days with repeated analyses of extracellular glucose, lactate, and glycerol concentrations. An additional analysis of pyruvate was performed in some patients to calculate the lactate-to-pyruvate ratio.This study showed that glucose, lactate, and glycerol change in a characteristic way when complete ischemia (i.e., complete inhibition of the blood circulation) is present. A slower stabilization with prolonged metabolic signs of ischemia, such as lower glucose and higher lactate and glycerol concentrations, was seen in zone II compared with zone I, and more pronounced metabolic signs of ischemia, but with a faster recovery, were detected in the free TRAM flap group than in the pedicled TRAM flap group. The fact that the metabolites returned to normal earlier in free flaps than in pedicled flaps may indicate that free TRAM flaps sustain less ischemic damage because of better and more vigorous perfusion.     

Successful use of muscle flaps or myocutaneous flaps in patients with sickle cell disease.

Sickle cell disease presents an unusual challenge to the reconstructive surgeon. The interaction between the underlying hemoglobinopathy and the circulatory mechanics in pedicled flaps leads to a high incidence of flap necrosis in patients with this disease. We present 3 patients with sickle cell disease in whom the use of axial flaps allowed the repair of difficult reconstructive problems in one stage, without preoperative exchange transfusions. The rationale for this approach is discussed.     

Properties and use of botulinum toxin and other microbial neurotoxins in medicine.

Crystalline botulinum toxin type A was licensed in December 1989 by the Food and Drug Administration for treatment of certain spasmodic muscle disorders following 10 or more years of experimental treatment on human volunteers. Botulinum toxin exerts its action on a muscle indirectly by blocking the release of the neurotransmitter acetylcholine at the nerve ending, resulting in reduced muscle activity or paralysis. The injection of only nanogram quantities (1 ng = 30 mouse 50% lethal doses [U]) of the toxin into a spastic muscle is required to bring about the desired muscle control. The type A toxin produced in anaerobic culture and purified in crystalline form has a specific toxicity in mice of 3 x 10(7) U/mg. The crystalline toxin is a high-molecular-weight protein of 900,000 Mr and is composed of two molecules of neurotoxin (ca. 150,000 Mr) noncovalently bound to nontoxic proteins that play an important role in the stability of the toxic unit and its effective toxicity. Because the toxin is administered by injection directly into neuromuscular tissue, the methods of culturing and purification are vital. Its chemical, physical, and biological properties as applied to its use in medicine are described. Dilution and drying of the toxin for dispensing causes some detoxification, and the mouse assay is the only means of evaluation for human treatment. Other microbial neurotoxins may have uses in medicine; these include serotypes of botulinum toxins and tetanus toxin. Certain neurotoxins produced by dinoflagellates, including saxitoxin and tetrodotoxin, cause muscle paralysis through their effect on the action potential at the voltage-gated sodium channel. Saxitoxin used with anaesthetics lengthens the effect of the anaesthetic and may enhance the effectiveness of other medical drugs. Combining toxins with drugs could increase their effectiveness in treatment of human disease.     

Versatility and reliability of combined flaps of the subscapular system

One-stage reconstructions of complex or unusually large defects frequently require composite tissue transfers. The various components of these "chimeric" flaps facilitate three-dimensional reconstructions or the coverage of large surface defects. Data from 36 combined flaps from the subscapular arterial system are demonstrated in this series. Defect locations were evenly distributed between the upper and lower extremities. Eighty-three percent were two-component flaps, and 17 percent contained three or more various tissue components. Overall flap survival was 97 percent. Major complications included vascular revisions in four patients and seven secondary skin transplantations. Five cases contained osseous components. The independent mobility of skin, muscle, and bone proved to be a major advantage in the reconstruction of compound defects. Donor-site morbidity was acceptable; the most frequent donor-site complication was persistent seroma in 9 of 36 patients (25 percent). Patient satisfaction was high. Ninety-one percent were satisfied with the operative result and would undergo the operation again. Eighty-six percent accepted the aesthetic appearance of the donor site. The data demonstrate that these complex flap procedures are extremely reliable and versatile, thus avoiding multiple reconstructive procedures and achieving excellent reconstructive results with acceptable donor-site morbidity.     

Neurology: botulinum toxin therapy for torticollis

The Scientific Board of the California Medical Association presents the following inventory of items of progress in neurology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers, or scholars to stay abreast of these items of progress in neurology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Neurology of the California Medical Association and the summaries were prepared under its direction.