Long-term Effects of Botulinum Toxin on Neuromuscular Function

Background: Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium.

Methods: Rats (n = 30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n = 9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated.

Results: Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups.     

Swimmer's view: a diagnostic adjunct for oesophageal foreign bodies

We describe the use of a common radiographic view of the lower cervical skeleton, 'Swimmer's View', to aid the diagnosis of foreign bodies in the upper oesophagus, which may be obscured by the clavicles. We further recommend this view when there is uncertainty over the nature of an impacted food bolus in this location, and luminal air is the only visible sign on a plain soft-tissue cervical radiograph.     

A role for iNOS in fasting hyperglycemia and impaired insulin signaling in the liver of obese diabetic mice

Chronic inflammation has been postulated to play an important role in the pathogenesis of insulin resistance. Inducible nitric oxide synthase (iNOS) has been implicated in many human diseases associated with inflammation. iNOS deficiency was shown to prevent high-fat diet-induced insulin resistance in skeletal muscle but not in the liver. A role for iNOS in fasting hyperglycemia and hepatic insulin resistance, however, remains to be investigated in obesity-related diabetes. To address this issue, we examined the effects of a specific inhibitor for iNOS, L-NIL, in obese diabetic (ob/ob) mice. iNOS expression was increased in the liver of ob/ob mice compared with wild-type mice. Treatment with iNOS inhibitor reversed fasting hyperglycemia with concomitant amelioration of hyperinsulinemia and improved insulin sensitivity in ob/ob mice. iNOS inhibitor also increased the protein expression of insulin receptor substrate (IRS)-1 and -2 1.5- and 2-fold, respectively, and enhanced IRS-1- and IRS-2-mediated insulin signaling in the liver of ob/ob mice. Exposure to NO donor and ectopically expressed iNOS decreased the protein expression of IRS-1 and -2 in cultured hepatocytes. These results suggest that iNOS plays a role in fasting hyperglycemia and contributes to hepatic insulin resistance in ob/ob mice.     

Cricothyroid approximation and subluxation in 21 male-to-female transsexuals

OBJECTIVES: To evaluate the medium-term outcome of cricothyroid approximation and subluxation (CTAS) with postoperative speech therapy for pitch elevation in male-to-female transsexuals. STUDY DESIGN: Retrospective study of male-to-female transsexuals who underwent pitch-raising surgery between November 1996 and August 2001. METHODS: Twenty-one male-to-female transsexuals opted for surgical feminization of their voices after inadequate improvements with speech therapy alone. Electrolaryngographic measurements were obtained by a single speech therapist of modal fundamental frequencies and the percentage of irregularities before, at 2 weeks, and 6 months after surgery. All 21 patients underwent CTAS, and 20 underwent simultaneous cosmetic thyroid chondroplasty by a single surgeon. RESULTS: Electrolaryngographic results 2 weeks after surgery showed an average postoperative gain in modal frequency of free speech of 71.05 Hz (95% confidence interval [CI]: 42.9-99.2, P < .001). There was a concomitant average rise in irregularities of 9.9% (95% CI 0.7-18.5, P = .03). At median follow-up of 6 months after six sessions of speech therapy (n = 15), there was a decrease in irregularities to preoperative levels. The overall gain at 6 months in modal frequency of free speech was 56.9 Hz (95% CI 38.3-75.4, P < .001). Smoking and age did not predict a worse outcome. CONCLUSIONS: Cricothyroid approximation effectively raises pitch in male-to-female transsexuals. There is a concomitant rise in voice irregularities that is effectively addressed by speech therapy.     

The disinfection of flexible fibre-optic nasendoscopes out-of-hours: confidential telephone survey of ENT units in England

We present the results of a confidential telephone survey of ENT units in England on the disinfection of flexible fibre-optic nasendoscopes out-of-hours. The on-call residents of 124 units were contacted and questioned. In 35.1 per cent of units surveyed, the on-call resident was primarily responsible for cleaning the scopes after use. Only 46 per cent of these junior doctors had access to a chemical sterilant to allow for high-level disinfection of these scopes. Provision for disinfection of scopes was poorer in teaching hospitals and in units that served inner city populations. Only 12.1 per cent of Senior House Officers (SHOs) received any training in disinfection techniques and only 25.5 per cent of units kept a register of patients nasendoscoped out-of-hours for purposes of contact tracing.     

A new technique for the management of inaccessible anterior glottic lesions

We describe a new technique for removing anterior vocal fold lesions, which cannot be visualized with conventional suspension laryngoscopy. These situations are rare and the only alternative surgeons have had previously is an open laryngeal procedure. The technique we describe involves the use of a laryngeal mask airway (LMA), a flexible bronchoscope with biopsy channel, a 400 microm laser fibre and KTP/532 nm laser. This method was used to treat two patients in whom conventional suspension laryngoscopy had previously been attempted and abandoned.     

New world mucosal and cutaneous leishmaniasis: an emerging health problem among British travellers

BACKGROUND: Mucosal leishmaniasis (ML) is an important complication of new world cutaneous leishmaniasis (CL) caused by species of the Leishmania Viannia subgenus. Previous reports of ML among travellers to Latin America are few. AIMS: To determine the annual number of cases of CL due to L. Viannia species diagnosed at this institution and to correlate this with changing patterns of travel. Secondly, to document the clinical presentation, diagnosis, treatment and outcome of ML at this institution. DESIGN: Retrospective observational study. METHODS: Data were collected from a clinical database, laboratory records, patient case notes and an international passenger survey. RESULTS: Between 1995 and 2003, the annual number of cases of CL (total 79) steadily increased from 4 per year to 18 per year; the estimated number of travellers from the UK to Latin America increased 3.5-fold. Six cases of ML were diagnosed among British travellers in 1995 (1), 1997 (1) and 2002 (4). These infections were acquired in Bolivia (3), Colombia (2) and Belize (1). Nasopharyngeal symptoms developed 0-15 months after returning to the UK. Four patients had concurrent CL at diagnosis. Diagnosis of ML was delayed up to 6 months from the onset of symptoms. Mucosal biopsies from all 6 patients were PCR-positive for L. (Viannia) DNA; microscopy and culture were less sensitive. ML relapsed in one patient following treatment. DISCUSSION: Increasing travel to Latin America from the UK was associated with an increasing number of diagnoses of L. Viannia CL. ML is likely to emerge as a more frequently imported infection among such travellers. Familiarity with these diseases is important for prompt diagnosis and optimal management.     

Pulmonary artery catheterization and thermodilution cardiac output determination in the management of critically burned patients

Pulmonary artery catheterization was performed in thirty-nine critically burned patients. Hemodynamic changes, induced by thermal injury and its therapy, were measured. Pulmonary wedge pressure was found to be a more reliable indicator of circulating volume, whereas central venous pressure was often misleading. Measurements of both pulmonary hemodynamics and cardiac output were necessary to manage patients requiring high levels of pulmonary end-expiratory pressure (PEEP). These measurements enable one to define optimum PEEP levels which provide maximum oxygen delivery to the tissues. Depressed myocardial function was seen in the early phase of the injury. In this period dopamine administration increased left ventricular stroke work index with minimal changes in filling pressures. The usefulness of dopamine in treating this early myocardial depression deserves further study. Catheter-related complications were minimal when the catheters were used for periods of three days or less.