Abuse of telazol: an animal tranquilizer

BACKGROUND: Telazol (tiletamine hydrochloride 50 mg/mL, zolazepam hydrochloride 50 mg/mL) is utilized in veterinary medicine as a small-animal anesthetic. Telazol is comparable to ketamine in efficacy, and in conjunction with ketamine, has been responsible for one reported human fatality. We report a case of a woman who abused telazol. CASE REPORT: A 30-year-old female employee at a local zoo was found unresponsive by fellow workers in a clean animal treatment room. Initial reports were that she had injected veterinary-grade diazepam and telazol. On-scene paramedics reported her as obtunded and arousable to deep painful stimuli, with gag reflex intact. Systolic blood pressure was 90 mm Hg by palpation. A fresh needle puncture mark was present on her right arm; nearby were a syringe, tourniquet, and bottles of each drug. Emergency Department assessment included airway, breathing, circulation, and intravenous access. She was lavaged and given activated charcoal with a cathartic. Shortly after arrival, she became alert and oriented. Family members insisted this was not an overdose. The patient had been previously evaluated for reported episodes of syncope, "only in the evening, while at work," and was prescribed diazepam for anxiety. Product information on telazol was limited to the Veterinary Drug Physician's Desk Reference. A urine drugs-of-abuse screen was positive for benzodiazepines and cannabinoids. The patient subsequently revealed a history of recreational use of telazol. She was discharged to an in-patient detoxification facility, 12 hours postadmission. CONCLUSION: Telazol used in veterinary medicine as an anesthetic agent, is structurally related to ketamine. Telazol causes almost immediate anesthetic effects, and sudden alertness is not uncommon as the effects of the drug subside. Urine drugs-of-abuse screens are unlikely to identify telazol. We report a veterinary worker who abused telazol.     

Angiopoietin growth factors and Tie receptor tyrosine kinases in renal vascular development

Angiopoietin-1 (Ang-1) is a secreted growth factor which binds to and activates the Tie-2 receptor tyrosine kinase. The factor enhances endothelial cell survival and capillary morphogenesis, and also limits capillary permeability. Ang-2 binds the same receptor but fails to activate it: hence, it is a natural inhibitor of Ang-1. Ang-2 destabilises capillary integrity, facilitating sprouting when ambient vascular endothelial growth factor (VEGF) levels are high, but causing vessel regression when VEGF levels are low. Tie-1 is a Tie-2 homologue but its ligands are unknown. Angiopoietin and Tie genes are expressed in the mammalian metanephros, the precursor of the adult kidney, where they may play a role in endothelial precursor growth. Tie-1-expressing cells can be detected in the metanephros when it first forms and, based on transplantation experiments, these precursors contribute to the generation of glomerular capillaries. During glomerular maturation, podocyte-derived Ang-1 and mesangial-cell-derived Ang-2 may affect growth of nascent capillaries. After birth, vasa rectae acquire their mature configuration and Ang-2 expressed by descending limbs of loops of Henle would be well placed to affect the growth of this medullary microcirculation. Finally, preliminary data implicate angiopoietins in deregulated vessel growth in Wilms’ kidney tumours and in vascular remodelling after nephrotoxicity. Received: 13 July 2000 / Revised: 6 September 2000 / Accepted: 11 September 2000     

Baclofen overdose: drug experimentation in a group of adolescents

BACKGROUND: Baclofen, a lipophilic analog of gamma-aminobutyric acid, is clinically used to control spasticity. We report a mass exposure to baclofen in adolescents seeking intoxication; toxicokinetic data are included. CASE SERIES: A group of adolescents became symptomatic after ingesting 3 to 30 20-mg tablets of baclofen during a party at a suburban Boys' Club. Several children were noted to be very lethargic by chaperones, ingestion was suspected, and paramedics were called. Some white tablets were found in a couch at the site of the party. The Massachusetts Poison Control Center was called, and the tablets were identified as baclofen (20 mg). Fourteen patients were taken to local hospitals; 9 required intubation. Eight adolescents were transferred to our institution. In these 8 patients, symptoms were noted within 1 to 2 hours after overdose. The most common clinical findings included coma (7), hypothermia (6), bradycardia (5), hypertension (4), and hyporeflexia (8). Mean length of mechanical ventilation was 40 hours. Three patients had unifocal premature ventricular contractions. Two patients had tonic-clonic seizures. A single dose of activated charcoal was given to all patients. Drugs administered included nifedipine (1), flumazenil (1), naloxone (1), lorazepam (2), and phosphenytion (2). All patients recovered and were discharged home within 5 days of ingestion. Serial serum baclofen levels were obtained in all intubated patients (range, 0.049 to 6.0; normal, 0.08 to .40 microgram/mL). Levels obtained 14 hours after ingestion showed a linear correlation with length of mechanical ventilation (R2 = 0.9863). Persistent symptoms were noted in some patients, despite nondetectable baclofen levels. Toxicologic screening for drugs of abuse was negative except in 2 patients with ethanol levels, both < 5 mg/dL. CONCLUSION: Baclofen overdose may result in coma, apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures. Levels obtained shortly after overdose correlate with length of mechanical ventilation.     

A single preoperative oral dose of valdecoxib,a new cyclooxygenase-2 specific inhibitor,relieves post-oral surgery or bunionectomy pain

BACKGROUND: The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery. METHODS: Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patient's Global Evaluation of Study Medication. RESULTS: In both studies, all doses of valdecoxib produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patient's Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events. CONCLUSIONS: Preoperative orally administered valdecoxib provides well-tolerated and effective analgesia for mild to moderate postoperative pain.     

Specialist training in rheumatology in Europe

Rheumatology is a broad discipline managing a spectrum of different conditions and there are divergences in what is routinely treated by rheumatologists both within and between countries. The free movement of doctors throughout the European Community has lead to moves to harmonize specialist training to ensure common standards of care. The Union Européene des Médecins Spécialistes (UEMS) has developed recommendations for the specialist training of rheumatologists in Europe that recognizes the broad definition of the discipline and the diversity of clinical practice in Europe. The core curriculum aims to provide a common standard around which to develop locally applicable national curricula. The provision of high quality care requires some assessment of training and competency as well as continuing professional development and ways of ensuring the provision of this throughout the European Community to a mutually high standard are being developed. The future may see more overlap in the training of all the disciplines concerned with the management of those with musculoskeletal conditions to their benefit.     

Health hazards for children at work

The International Labor Office has estimated that there are 250 million child laborers (5-14 years old) worldwide, with more than 120 million of these working full-time. The issue is complex; child labor is an economic and social reality in many developing countries. Children may provide 25% or more of a family's total income, and many traditional cultures include child labor as an integral part of the child's socialization and achievement of status in the local community. Governments may regard child labor as a key factor in keeping their economy competitively viable through the provision of cheap labor for commercial interests. And yet child labor violates children's rights and exposes them to increased health risks. Children who work full-time do not attend school and thereby lose their inherent right to an education. They may come from families ravaged by poverty, live in dilapidated housing, have unsafe water supplies, poor sanitation, and inadequate nutritious food. Working children are vulnerable to anemia, fatigue, early initiation of tobacco smoking, and other health problems. Manual labor exposes children to injury and also to poisoning from chemicals such as solvents, pesticides, metals, caustic agents used on the job, to fumes and dust, and other toxic, work-related byproducts. The International Labor Organization has sought to control the most abusive of child labor practices throughout the world. Solutions to this complex and intractable worldwide problem will also require infrastructure changes in the economic and social incentives to child labor, enlightened public health policies, and community-level advocacy and involvement.     

Nail primer cosmetics: correlations between product pH and adequacy of labeling

BACKGROUND: We have previously reported on injuries suffered by young children exposed to methacrylic acid-containing nail primers and the need for public education efforts concerning this potential household hazard. However, some primers contain alternative ingredients, which may or may not pose the same risk; product labeling information is variable and may be confusing to consumers. OBJECTIVE: To investigate the relationship between pH of different primer products, product contents, and appropriateness of product labeling and packaging. METHODS: Twenty-three commercially available primers were grouped by product contents: (methacrylic acid vs others). Product pH was measured and product labels were scored on 7 warning points: "poison and/or corrosive," a "caution to avoid contact and/or to use a barrier when handling the product," a "skin first aid," and "eye first aid," an "ingestion first aid," a caution to "keep out of reach of children," and a "in emergency, contact a poison center." A summative "global hazard notification score" was calculated for each product. Data were analyzed using correlations and the two-sample t-test. RESULTS: None of 23 products tested were contained in a child-resistant container and none included all 7 label items. Product pH ranged from 1.90-8.55 (mean pH 4.59 +/- 1.99); 20 products had pH < 7.0. Only 1 product advised, in the event of a poisoning, that a poison center be contacted. Of 20 acidic products, only 7 alerted users that the contents could cause burns. The mean global hazard notification score (MAX = 7) was 3.6; global hazard notification score did not correlate with pH. Methacrylic acid-containing products had a lower pH (mean 3.43 +/- 0.78) than those without methacrylic acid (mean 5.34 +/- 2.18), p = 0.008. When the primer bottle was separated from the rest of the packaging which comprised the artificial nail "kit," 50% of products lost all of their warning information. CONCLUSIONS: Most, but not all, artificial nail primers analyzed in this study were highly acidic. Labeling and packaging of many nail primers are inadequate, given the potential of methacrylic acid in these products to cause burns and the toxicity of most nail primers. We agree with the Consumer Product Safety Commission's recently proposed rule to require cosmetic manufacturers to repackage methacrylic acid-containing household products in child-resistant containers. We also urge manufacturers to alert consumers to the hazards of nail primers by better labeling. Manufacturers should also investigate the feasibility of either substituting other chemicals or lowering the concentration of methacrylic acid.     

Care of elderly patients with a fractured neck of femur

This survey was designed to compare the clinical management of elderly patients admitted to hospitals with a hip fracture, with the recommendations in the recent Royal College of Physicians report "Fractured Neck of Femur". The results highlight large discrepancies between the 'ideal' clinical management as recommended, and that which occurs in practice. Particular concerns include the lack of experienced medical supervision provided for patients perioperatively, the high proportion of junior anaesthetic and surgical staff performing the operation, and the widespread poor rehabilitation facilities. These findings suggest that, unless the quality of clinical care for such patients is vastly improved, the predicted exponential rise in the number of elderly people sustaining a hip fracture will create a heavy burden on scarce National Health Service resources.