An outbreak of cutaneous infection due to Mycobacterium abscessus associated to mesotherapy.

INTRODUCTION: In February 2009 an outbreak of subcutaneous abscesses due to Mycobacterium abscessus was detected in Spain which affected healthy women who had undergone mesotherapy procedures in an aesthetic clinic. METHODS: Epidemiological research, health inspection and microbiological studies were conducted. The patients were given antibiotic treatment (according to susceptibility testing) with clarithromycin, and in some cases, combined with amikacin. RESULTS: Seventeen out of 77 patients treated in the clinic were affected. The products used for the injections were homeopathic drugs in multi-dose vials. The environmental samples were negative. The sterile injection equipment and the clinical procedures were evaluated as correct. The storage conditions for the drugs were also correct, and all the samples tested negative for Mycobacteria. However Paenibacillus provencensis was isolated from samples of unused multi-dose vials and the withdrawal of the product from distribution was ordered. Deficiencies were detected in the sterile products process of at the homeopathic drug factory, so the production line was suspended. CONCLUSIONS: The results of environmental investigation suggest the most likely cause of the outbreak could have been the contamination of the products in the factory, although there was no laboratory confirmation. The widespread use of homeopathic products in invasive procedures requires extreme control during the manufacturing, handling and packaging process. It is important to consider mesotherapy and parenteral use of homeopathic medicines as potential sources of infection and therefore the same precautions in the procedures and quality assurance of products should be applied as with any other drug or medical activity.

A series of case reports: clinical evaluation of a complex homeopathic injection therapy in the management of pain in patients after breast cancer treatment.

OBJECTIVE: In breast cancer patients, posttreatment pain often appears after several months and strongly impairs health-related quality of life. Conventional methods of pain reduction are often ineffective. Injection therapy with Traumeel (Heel GmbH, Baden-Baden, Germany), a medication with analgesic properties used in homotoxicology for treatment of the pain associated with trauma as well as a mediator of inflammation, was proposed as an innovative approach for pain relief after breast cancer treatment. DESIGN: Nine patients, still suffering from a high level of pain after breast cancer therapy despite use of postoperative treatment with conventional analgesics, were invited to participate. A Traumeel and procaine injection was administered once a week for three to 10 sessions. The level of pain was assessed by a pain score and physical and psychological status by a questionnaire before and directly after injection and again at follow-up visits after 3 and 6 months. RESULTS: After the last injection, all patients experienced a marked reduction of their level of pain on average from 7.6 +/- 1.5 to 2.4 +/- 1.4 points on a scale from 1 to 10 points. After a followup observational phase of 3 and 6 months, pain score ratings increased slightly again in some patients but remained consistently low in others. In any case, the ratings of pain levels did not reach the values assessed before the start of Traumeel injection. Similarly, health-related quality of life improved with this injection therapy. The perception of pain relief with Traumeel injection was high in 8 of 9 patients, reflecting an overall perceived positive outcome and tolerability of this treatment. CONCLUSIONS: This case series represents a first encouraging approach to using this complex homeopathic injection for pain relief in breast cancer patients.

Achilles tendon rupture in an elite athlete following multiple injection therapies.

Achilles tendinopathy is common, and its management continues to be challenging, especially in elite athletes. Despite a wide range of novel management options, none guarantees a rapid return to high level sporting activity. Eccentric exercise has been shown to reduce symptoms and normalise imaging abnormalities, but time constraints on professional athletes often make this an unrewarding isolated management strategy. Eccentric exercises concurrent with ongoing training may not be as successful as eccentric training alone, reducing one's confidence in this modality for the "in-season" tendinopathy in the elite athlete. When a professional athlete is faced with a tendinopathy recalcitrant to eccentric exercise, manual therapy and orthotics, a more invasive approach is often attempted to expedite a return to unencumbered training. Numerous injection therapies are described, ranging from homeopathic products to glucocorticosteroids. The robustness of the literature surrounding these techniques is variable, but when an athlete is desperate to return to full training, clinicians working with elite athletes are often tempted to utilise more empirical management options. We present a patient who illustrates the potential dangers of injection therapy in the elite athlete, in particular sequential injection therapy involving vascular sclerosants, which to our knowledge has not previously been described. Written consent for the presentation of this case was obtained from the athlete concerned.

Cosmetic mesotherapy: between scientific evidence, science fiction, and lucrative business.

Mesotherapy, originally conceived in Europe, is a minimally invasive technique that consists of the intra- or subcutaneous injection of variable mixtures of natural plant extracts, homeopathic agents, pharmaceuticals, vitamins, and other bioactive substances in microscopic quantities through dermal multipunctures. Its application in cosmetic medicine and surgery is gaining in popularity and acceptance and is rapidly growing in profile at an alarming rate. Despite their attraction as purported rejuvenating and ''fat-dissolving'' injections, the safety and efficacy of these novel cosmetic treatments remain ambiguous, making mesotherapy vulnerable to criticism by the generally more skeptical medical community. The technique is shrouded in mystery and the controversy surrounding it pertains to its efficacy and potential adverse effects that are subject of much concern. As with any new technology, it is important to assess the benefits, safety, experience, and standardization of mesotherapy. More studies are necessary before it can be advocated as a safe and effective treatment for body contouring and facial rejuvenation. Although the claims made about mesotherapy may be hard to believe at face value, we must be cautious about rejecting new ideas. Just as absence of proof is not proof of absence, lack of scientific validation is not proof that it does not work.

Homeopathic mistletoe adverse reaction mimics nodal involvement in 18F-FDG PET/CT performed for evaluation of response to chemotherapy in lymphoma.

Some patients use complementary medicine. We present a patient with Hodgkin's lymphoma, scanned with 18F-FDG PET/CT for evaluation of response after chemotherapy, who was self-administering mistletoe as a homeopathic medicine product. The careful review of the images of the entire scan and patient collaboration in anamnesis were crucial to avoid a false positive result. A review of the published scientific data on the effects of mistletoe is also presented.

Phagocytosis, endosomal/lysosomal system and other cellularaspects of macrophage activation by Canova medication.

Canova is a homeopathic medication with immunomodulatory properties, recommended for diseases where the immune system is depressed. Our research aims to study the activation of mice peritoneal macrophages when submitted to in vivo and in vitro Canova treatment. Morphological parameters and acid phosphatase activity were analyzed using light and transmission electron microscopy. Differential interference contrast microscopy, including serial time acquisition in living cells, was also performed. The results demonstrated a greater spreading ability in Canova treated macrophages, a higher phagocytic activity of non-infective microorganisms (Saccharomyces cerevisiae and Tripanosoma cruzi epimastigotes) and a tendency to lower the phagocytic activity of the infective microorganisms T. cruzi trypomastigotes and Leishmania amazonensis, when compared with control cells. Acid phosphatase activity was analyzed and showed that Canova treatment stimulates an increase of the endosomal/lysosomal system. Treated macrophages that do or do not interact with yeast present a higher number of acid phosphatase marked vesicles compared to control cells. In contrast, the activity of tartrate resistant acid phosphatase (TRAP), is lower in Canova treated macrophages. The net results demonstrate that Canova medication is an effective stimulator of macrophage activity.

Safety of homeopathic injectables for subcutaneous administration: a documentation of the experience of prescribing practitioners.

OBJECTIVES: The aim of this study was to chart the experiences of homeopathic injectables prescribing practitioners with regard to safety issues and the extent in which these practitioners would feel restricted in case subcutaneously administered homeopathics were banned. DESIGN: This was a survey among practitioners who prescribe homeopathic injectables in 12 European countries. SUBJECTS: Data were gathered from 1693 doctors experienced in the use of homeopathic injectables for subcutaneous use. The data are based on experience with an estimated 36 million patient contacts. RESULTS: Of the 1693 doctors 1594 (94.2%) choose subcutaneous administration because of its therapeutic effect. 96.4% of the doctors never, very rarely, or rarely, observed any adverse reactions because of the subcutaneous form of application. The reported adverse reactions were mostly harmless (local redness, hematoma, local pain). Of the doctors, 98.1% never, very rarely, or rarely observed any adverse reactions caused by the specific homeopathic medicinal product used. In addition, 99.5% of the doctors desire homeopathic injectables for subcutaneous use to stay on the market and 89% would be severely or very severely limited in their profession if homeopathic injectables were not available. CONCLUSIONS: The study suggests that homeopathic injectables have a very low risk profile. A very small number of severe adverse reactions (anaphylactic reaction, feverish symptoms, aversion/anxiety against injections, and asthma) have been reported with products with a concentration higher than 1:10,000.

Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility.

In a double-blind, placebo-controlled, randomized study, 55 anovulatory subjects received a single s.c. injection of placebo (n = 10) or recombinant long-acting FSH [FSH-carboxy terminal peptide (CTP), ORG 36286, corifollitropin alfa; NV Organon, The Netherlands] in doses of 7.5 (n = 13), 15 (n = 10), 30 (n = 11), or 60 microg (n = 11). The injection was given 2 or 3 d after the onset of a spontaneous or progestagen-induced withdrawal bleed. After drug administration, the induced follicular response varied widely among subjects in each dose group. The percentage of subjects with a follicular response (at least one follicle > or = 10.0 mm) increased with the dose (P < 0.01) and was 10, 31, 70, 73, and 82% in the placebo and 7.5-, 15-, 30-, and 60-microg treatment groups, respectively. In responding subjects, the average maximum number of follicles was 4.0, 7.6, 13.4, and 20.0, respectively, which was reached at 6.5, 6.9, 6.6, and 8.2 d after a single dose of 7.5, 15, 30, and 60 microg FSH-CTP, respectively. The dose-response for the number of follicles was statistically significant within the dose range tested (P < 0.01). Peak serum inhibin-B levels were significantly correlated with serum estradiol (E2) levels (r = 0.84, P < 0.01), and peak concentrations of inhibin-B and E2 correlated with the number of follicles observed at the same time point (for both hormones; r = 0.47, P < 0.01). Overall per treatment group, serum E2 and inhibin B concentrations significantly increased only in the two highest FSH-CTP dose groups, reaching peak concentrations at d 3 in the 30-microg group and at d 5 in the 60-microg group. Thereafter these hormone values declined rapidly, returning to baseline within 1 wk after FSH-CTP administration. In total, nine of the 55 treated subjects (16.4%) ovulated after drug administration: one subject in the placebo group, two subjects in the 7.5-microg group, three subjects in the 15-microg group, two in the 30-microg group, and one in the 60-microg group. Three subjects had monofollicular ovulation after placebo (n = 1) and a single dose of 15 microg FSH-CTP (n = 2). In two subjects with too many preovulatory follicles, (multiple) ovulation was prevented by GnRH antagonist administration. Thus, a single low dose of long-acting FSH-CTP was able to induce one or more follicles to grow up to ovulatory sizes, but the anovulatory status was not reversed because the incidence of subsequent (mono)ovulations was low.

Urofollitropin - Ferring: FERRING hFSH, hFSH - Ferring, human follicle-stimulating hormone - Ferring, Bravelle.

Ferring Pharmaceuticals (US) is developing a highly purified form of urofollitropin [human follicle-stimulating hormone, hFSH, FERRING hFSH, Bravelle] for use in ovarian stimulation in fertility treatments. The highly purified human-derived follicle-stimulating hormone (HP-FSH), administered by either intramuscular (IM) or subcutaneous (SC) injection, was in phase III trials in the US and in May 2002 the product received US FDA approval for use in conjunction with human chorionic gonadotropin for infertility patients undergoing ovulation induction. The product will be marketed as Bravelle. Ferring Pharmaceuticals has also submitted a New Drug Application for additional indications for Bravelle in infertility treatment, which is currently under review by the US FDA. Bravelle is produced from the urine of menopausal women and has been shown to be as effective as Organon's recombinant FSH product, Follistam. Preclinical studies have shown that Ferring Pharmaceuticals' hFSH can be mixed in the same syringe as purified human menopausal gonadotropin (hMG) to reduce the number of daily injections required in ovarian stimulation protocols without altering the bioactivity of FSH or luteinising hormone. In addition, Ferring Pharmaceuticals' hFSH administered SC or IM showed positive results compared with SC Repronex in a randomised, open-label study in patients undergoing in vitro fertilisation.Ferring Pharmaceuticals has teamed up with the American Infertility Association and RESOLVE: the National Infertility Association to improve access to infertility treatment in the US, with the recent launch of the 'Bravelle' HEART (Helping Expand Access to Reproductive Therapy) Programme. The programme is intended to provide urofollitropin treatment at significant cost savings to patients and their physicians. Serono is also developing a highly purified urofollitropin product.

A prospective, randomized study to assess the tolerance and efficacy of intramuscular and subcutaneous administration of recombinant follicle-stimulating hormone (Puregon).

OBJECTIVE: To compare local tolerance and clinical efficacy after i.m. or s.c. injection of recombinant FSH (Puregon; NV Organon, Oss, The Netherlands). DESIGN: An open-label, prospective, randomized, group-comparative, multicenter study. SETTING: Twelve IVF clinics in 10 countries. PATIENT(S): Two hundred eighteen infertile pituitary-suppressed women undergoing IVF-ET were randomized, of whom 195 (i.m., n = 77; s.c., n = 118) received recombinant FSH. INTERVENTION(S): One cycle of controlled ovarian hyperstimulation induced by either i.m. or s.c. injection of recombinant FSH, followed by IVF-ET. MAIN OUTCOME MEASURE(S): Local tolerance symptoms, number of oocytes retrieved, ongoing pregnancy rate. RESULT(S): The incidences after i.m. injection of bruising, pain, redness, swelling, and itching were 37.7%, 31.2%, 13.0%, 7.8%, and 6.5%; after s.c. injection, the corresponding figures were 54.2%, 28.0%, 16.1%, 5.9%, and 3.4%. Only bruising was significantly lower in the i.m. group, which could be attributed to the more visible superficial injection site with s.c. administration. The overall occurrence of local symptoms were 63.6% after i.m. injection and 68.6% after s.c. injection. The mean numbers of oocytes recovered were 9.8 (i.m) and 10.4 (s.c.) and the ongoing pregnancy rates per attempt were 27.1% (i.m.) and 26.1% (s.c.), respectively. CONCLUSION(S): There were no marked differences in local tolerance symptoms and clinical efficacy between i.m. and s.c. administration of recombinant FSH.

Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers.

OBJECTIVE: To assess the absolute bioavailability of ganirelix (Antagon/Orgalutran; NV Organon, Oss, the Netherlands) after a single SC injection. DESIGN: Randomized, crossover, pharmacokinetic study. SETTING: Phase I clinical research unit. PATIENT(S): Nineteen healthy female volunteers of reproductive age. INTERVENTION(S): Two separate injections of 0.25 mg of ganirelix were given, one subcutaneously and one intravenously, with a washout period of 1 week between injections. Blood samples were taken for assessment of serum ganirelix concentrations, and blood pressure, heart rate, and adverse events were monitored. MAIN OUTCOME MEASURE(S): Pharmacokinetic parameters. RESULT(S): Fifteen subjects were evaluated. The mean concentration-time profile after SC administration was comparable to that after IV administration. The mean (+/- SD) peak concentration and time of occurrence after SC administration were 14.8+/-3.2 ng/mL and 1.1+/-0.3 hours, respectively. The mean (+/- SD) half-lives after IV administration and SC administration were highly similar (12.7+/-3.7 hours and 12.8+/-4.3 hours, respectively). Mean (+/- SD) AUC0-infinity (area under the concentration-time curve) values of 105+/-11 ng/mL x hours and 96+/-12 ng/mL x hours were calculated for IV administration and SC administration, respectively, resulting in an absolute mean (+/- SD) bioavailability of 91.3%+/-6.7%. Both treatments were well tolerated. CONCLUSION(S): Ganirelix is absorbed rapidly and extensively after SC administration, resulting in a high absolute bioavailability of >90%.

Subcutaneous bupivacaine for postoperative analgesia after herniorrhaphy.

Subcutaneous injection of bupivacaine around the wound was used to provide postoperative analgesia in patients who had undergone herniorrhaphy. This proved to be an effective means of providing postoperative pain relief with no unwanted general or local effects.

[Antagonism to neuromuscular effect of subcutaneous administration of pancuronium by neostigmine].

It has been reported that subcutaneous administration of pancuronium produces prolonged neuromuscular blockade. The purpose of this study was to evaluate the antagonistic effect of neostigmine on neuromuscular blockade following subcutaneous injection of pancuronium in anesthetized patients. Fourteen male patients aged 32-67 yr, weighing 50-58 kg, and scheduled for surgical operation lasting more than 6 hr were included in the study. None of the patients had paresis. Anesthesia was induced with thiamylal and SCC. Patients under N2O-oxygen-enflurane (1.0-1.5%) anesthesia, were divided into two groups (n = 7 in each group). Group A was given an intravenous bolus of pancuronium 6 mg. Group B received pancuronium 6 mg subcutaneously in the ankle. Train-of-four responses were evaluated every 12s by measuring the force of thumb adduction produced in response to supramaximal stimulation of the ulnar nerve at the wrist. When the train-of-four ratios recovered to approximately 0.2 in groups A and B, a mixture of neostigmine 1.0 mg and atropine 0.5 mg was administered. The onset of fade in train-of-four responses was significantly more rapid in group A (intravenous administration) than in group B (subcutaneous administration). Time intervals to maximum train-of-four depression from pancuronium administration in groups A and B averaged 2.6 and 125.4 min, respectively. No significant differences in the recovery times of the train-of-four ratios from 0.2 to 0.7 following neostigmine administration in groups A and B were demonstrated. None of the patients who received pancuronium subcutaneously showed recurarization following neostigmine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholic extract of tarantula cubensis improves sharp ruptured tendon healing after primary repair in rabbits.

This study was designed to investigate the effects of tarantula cubensis (TC) on the superficial digital flexor tendon (SDFT) rupture after surgical anastomosis, on day 84-postinjury (DPI) in rabbits. Forty white New Zealand, mature, male rabbits were randomly and evenly divided into treated and control groups. After tenotomy and primary repair, the injured legs were immobilized for 2 weeks. TC was injected subcutaneously over the lesion on 3, 7, and 10 DPI. The control animals received subcutaneous injections of normal saline similarly. Animal's weight, tendon diameter, clinical status, radiographic and ultrasonographic evaluations were recorded at weekly intervals. The animals were euthanized on 84 DPI and the injured tendons and their normal contralaterals were evaluated for histopathologic, histomorphometric, ultrastructural, biomechanical, and percentage dry weight parameters. Treatment significantly improved the clinical performance, cell, collagen and tissue maturation, tissue alignment and remodeling, ultimate strength, stiffness, maximum stress, and dry weight content and decreased the tendon diameter, inflammation, adhesions and degeneration of the injured treated tendons compared to the injured control ones. The present findings showed that TC is effective on sharp ruptured SDFT in rabbits and it could be one of the novel therapeutic options in clinical trial studies.

Position paper on mesotherapy.

Mesotherapy is a controversial cosmetic procedure which has received publicity among the lay people, in the internet and in the media. It refers to minimally invasive techniques which consist of the use of intra- or subcutaneous injections containing liquid mixture of compounds (pharmaceutical and homeopathic medications, plant extracts, vitamins and other ingredients) to treat local medical and cosmetic conditions. This position paper has examined the available evidence and finds that acceptable scientific evidence for its effectiveness and safety is lacking. IADVL taskforce, therefore would like to state that the use of this technique remains controversial at present. Further research and well-designed controlled scientific studies are required to substantiate the claims of benefit of this mode of therapy.

A retrospective comparison of clinical outcomes and satisfaction using reconstituted recombinant gonadotropins (rFSH) or cartridge rFSH with a pen device in donor oocyte cycles.

BACKGROUND: Use of recombinant follicle stimulating hormone (rFSH) in a cartridge pen device offers obvious benefits for donor oocyte cycles including the administration of fewer and more patient-friendly injectable medications. METHODS: In a University-based IVF program, a total of 98 oocyte donor cycles using rFSH either reconstituted or as a pen device given to 118 recipients (eight split cycles) were retrospectively reviewed. Following discontinuation of oral contraceptive, controlled ovarian hyperstimulation was begun using either reconstituted rFSH (n = 19) or rFSH with a cartridge pen device (n = 79) (150-300 IU qd). GnRH-antagonists (Ganirelix, Organon) and an additional 75 IU of rFSH/day were begun when lead follicles were 13-14 mm in greatest diameter. The primary endpoints analyzed included cycle stimulation characteristics for each donor group and donor medication tolerance assessment with respect to each rFSH formulation, while secondary outcome measures included clinical pregnancy and implantation rates. RESULTS: Oocyte donors using the pen required significantly less rFSH (2734 IU vs. 3276 IU, p < 0.05) and scored significantly higher medication tolerance scores (3.9 +/- 0.4 vs. 3.1 +/- 0.6, p < 0.05). No other differences in cycle stimulation for oocyte donors and clinical outcomes for recipients were seen including pregnancy rates (pen, 77% vs. reconstituted, 55%, p - NS) and clinical pregnancy rates (61% vs. 45%, p - NS). However, significantly greater implantation rates (57% vs. 31%, p < 0.01) occurred in the pen group. CONCLUSION: Compared to reconstituted formulations, the pen device results in lower gonadotropin requirements and provides a simplified dosing method with better tolerance.

[Injectable homeopathic treatment in patients with backache. An approach]. / Homéopathie injectable chez le lombalgique. Une approche.

Among unaccustomed treatments for low back pain homeopathy matter given by injection has been joined with usual care. Preliminary results have to be confirmed by controlled studies.