Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine.

INTRODUCTION: Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability. CASE REPORT: A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 µg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes. DISCUSSION: Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.

Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease.

Dietary restriction (DR) extends lifespan in diverse organisms and, in animal and cellular models, can delay a range of aging-related diseases including Alzheimer's disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression. Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant Aß42 and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented by dietary manipulation. Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aß and tau pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in the pathogenesis of AD.

Radiation transfer effects on the spectra of laser-generated plasmas.

Experimental x-ray spectra of the H-like 2p --> 1s (Lyman-alpha) doublet have been obtained using time-integrated high-resolution spectroscopy of a constrained-flow, laser-generated aluminum plasma. These spectra show monotonic alteration of the relative intensities of the doublet components with distance from the target surface. Excellent agreement between experiment and theory is found only if the modeling includes both ion collisional rates between the fine-structure components of the level and, more importantly, the radiative pumping of one Lyman-alpha component by the other component along the direction of the major velocity gradient (i.e., perpendicular to the direction of spectra observation). Understanding radiation transfer in plasmas with high velocity gradients is important in modeling many astrophysical objects, and this experiment acts as a benchmark for such complex calculations.

Atypical presentation of tuberculosis meningitis: a case report.

A 19 year old woman presented with atypical symptoms of tuberculous meningitis. Meningitis is the most serious form of tuberculosis (TB) and it often presents with nonspecific signs and symptoms. Delayed diagnosis can result in rapid progression of neurological deficits and poor prognosis. Polymerase chain reaction and other nucleic acid amplification methods are becoming increasingly useful for the rapid detection of Mycobacterium tuberculosis in the cerebrospinal fluid. Early treatment reduces morbidity and mortality of this serious condition.

Neurogenic pulmonary oedema induced by bacterial meningitis: a case report.

We report a case of neurogenic pulmonary oedema occurring in association with bacterial meningitis. An 87 year old man suddenly developed severe dyspnoea without cardiac failure (MUGA scan ejection fraction 47%). Radiographs showed pulmonary oedema. A few hours later he developed signs of meningitis and lumbar puncture suggested a partially treated bacterial meningitis. We suspect that the bacterial meningitis had induced neurogenic pulmonary oedema.

Lessons to be learned: a case study approach a case study of the temporal onset of pulmonary hypertension with pre-existent cirrhotic portal hypertension.

We report the occurrence of pulmonary hypertension in a 37-year-old male patient with cirrhosis of the liver, portal hypertension and oesophageal varices. Although this is a rare combination, previous reports have shown that the association of portal and pulmonary hypertension is not coincidental; the temporal onset of primary pulmonary hypertension is hard to predict and our patient was asymptomatic for a number of years. The pathogenesis of portal hypertension leading to pulmonary hypertension is not known. Diagnosis is difficult because the clinico-pathological symptoms in both conditions are similar. Treatment is limited to calcium channel blockers, vasodilators, nitrous oxide and prostacyclin, although most patients will eventually require visceral transplantation.

Experience of a small British pacing centre between 1994 and 2000: some answers to the problem of low UK implantation rates.

Raigmore is a district general hospital offering a permanent pacemaker service to its catchment population of 233,500. This report reviews the pacemaker practice over a seven year period (1994 to 2000) and makes a comparison with the national database and other hospitals in the UK. The records of all patients receiving new implantions for the period under observation were reviewed retrospectively. Data collected included number of patients paced each year, age, sex, indications and complications. In the 84 months studied 3/71 patients received new permanent pacemakers (the mean age was 74 years and 51% were male). The most common presenting symptoms were syncope (62%), dizzy spells (24%), and heart failure (11.5%). The most common indication for permanent pacemaker insertion was complete atrioventricular block (58%) followed by sick sinus syndrome (20%). The implantation rate was 419.3/million population/year in 2000. Pacemaker modes used were appropriate and the early and late complication rates were low (2.7%). This current audit demonstrates continued growth of the service with low-complication rates and implantation rates which approach those in Western Europe and North America.

Normalisation of abnormal coronary fractional flow reserve associated with myocardial bridging using an intracoronary stent.

Although intracoronary stenting procedures have been advocated for the successful treatment of myocardial ischaemia associated with myocardial bridging, the physiological rationale for this approach remains unexplored. The case of a 70 year old man with symptoms of cardiac ischaemia associated with a left anterior descending coronary artery bridge is described, where use of an intracoronary stent abolished the angiographic abnormalities and also restituted pronounced abnormalities of coronary fractional flow reserve.

Carboprost exposure in a newborn with recovery.

BACKGROUND: This case describes a newborn who was accidentally given carboprost (Hemabate) 250 micrograms intramuscularly, the largest amount ever reported in a normal newborn. CASE REPORT: A full-term newborn was inadvertently given carboprost rather than his prescribed hepatitis vaccine. Within 15 minutes, he was tachypneic and hypertensive followed by bronchospasms and dystonic movements and/or seizure activity of his upper extremities. He also was hyperthermic and had diarrhea stools. He recovered within 18 hours and was discharged. CONCLUSION: The manufacturer reports 2 infants who received lesser amounts and remained asymptomatic. This child exhibited symptoms associated with an overdose of a prostaglandin F2a, although complete recovery occurred within 18 hours.

Miliary tuberculosis presenting as infection of a pacemaker pulse-generator pocket.

A seventy year old woman had a permanent VVI pacemaker inserted in 1983 for complete heart block and presented ten years later with purulent discharge from the generator pocket. During a prolonged pyrexial illness, she developed renal and respiratory failure and her illness was complicated by recurrent ventricular fibrillation. The patient died on her 31st hospital day. Subsequent histological and microbiological investigation revealed widespread miliary tuberculosis which included involvement of myocardial tissue, great vessels and the pacemaker pocket. To our knowledge, this is the first reported occurrence of miliary tuberculosis involving a permanent pacemaker system. Furthermore, the granulomatous myocarditis which occurred as part of the miliary picture is a rare occurrence and possibly explains the recurrent ventricular fibrillation.

Permanent pacemaker practice at a Scottish district general hospital between 1987 and 1993.

BACKGROUND: Raigmore is a district general hospital offering a permanent pacemaker service to its catchment population of 233,500. It has been argued that the British public would be better served by a less centralised pacing service. There also exists the view, however, that a lower rate of complications and best follow up practice are achieved by specialised centres. The pacemaker practice over a 79 month period (January 1987 to July 1993) was thus reviewed with these issues in mind. METHODS: The pacemaker records of all new implantations for the period under observation were reviewed retrospectively. Data were acquired under the headings age, sex, symptoms, electrocardiographic (ECG) indications, and complications (early and late). Comparison was made with United Kingdom national data, a previous audit from Raigmore, and two recently published large series from specialist centres (one British and the other French). RESULTS: The mean age of patients who underwent implantation was 74 years and 47.5% were male. The most common presenting symptoms were syncope (46%), dizzy spells (24.5%), and heart failure (11.5%). The most common ECG indications for pacing were complete heart block (wide QRS) (28%), atrial flutter/fibrillation with bradycardia (21.6%) and complete heart block (narrow QRS) (9.6%). The implantation rate was 184/million population/year in 1993. The early and late complication rates were low (2.48%). CONCLUSIONS: The presence of a pacing centre in a remote part of the United Kingdom fulfils a necessary service and has low complication rates, with implantation rates and patterns that are comparable with those in other parts of the country.

Arrhythmogenic right ventricular dysplasia: an uncommon cause of ventricular tachycardia in young and old?

Right ventricular dysplasia is a little understood condition and is almost certainly underdiagnosed as an important cause of recurrent ventricular tachycardia and sudden death. This report describes two patients with right ventricular dysplasia. Their clinical presentation reflects the remarkable diversity of the disease while the potentially life-threatening nature of their arrhythmias and their lack of response to medical treatment justified the antiarrhythmic surgical procedure of right ventricular disarticulation.

Safety of fibreoptic endoscopy: analysis of cardiorespiratory events.

Cardiorespiratory function during upper gastrointestinal endoscopy and colonoscopy was studied prospectively in 164 patients. Cardiorespiratory events, which were defined as oxygen saturation < 90 per cent, electrocardiographic changes, heart rate < 50 or > 100 beats/min and systolic blood pressure < 100 mmHg, occurred in 111 patients. In 24 of these, changes were attributed solely to intravenous sedation. In the remaining 140 patients, events were noted in 34 (52 per cent) of 66 upper gastrointestinal endoscopies and during 53 (72 per cent) of 74 colonoscopies. One patient suffered a myocardial infarction during colonoscopy. Although cardiorespiratory events were common (111 of 164; 68 per cent), the actual morbidity rate was low (one of 164; 0.6 per cent). Cardiorespiratory events were significantly more common in patients with a history of cardiac disease for both upper gastrointestinal endoscopy and colonoscopy (overall chi 2 = 7.41, 1 d.f., P < 0.05) and more common for oesophageal dilatation than for diagnostic endoscopy (chi 2 = 5.56, 1 d.f., P < 0.05). It is recommended that patients with a history of cardiac problems undergoing upper gastrointestinal endoscopy or colonoscopy and all those requiring therapeutic endoscopy should be monitored carefully to allow early detection of cardiorespiratory events, and that oxygen should be administered routinely.

Could it be myotonic dystrophy? Myotonic dystrophy presenting with atrial flutter.

Myotonic dystrophy is a well recognised and well defined multisystem disorder which is inherited in an autosomal dominant fashion through a locus on chromosome 19. The disease itself is characterised by rigidity and degeneration of skeletal muscle, cataract formation, gonadal atrophy, frontal baldness and mental retardation. Like many inherited disorders there is a variable expression and so diverse clinical presentations can occur.

Nurturing mission. A case study of a hospital's cultural growth.

Recognizing the need to enhance his hospital's fulfillment of its mission as a religious organization, the chief executive officer of Lutheran Hospital of Indiana, Inc., Fort Wayne, initiated a process to change the institution's corporate culture to reflect the mission. After assessing hospital managers' perceptions of the hospital's mission, a planning committee drafted a mission statement. The statement was condensed into an easily remembered motto, "Reach out and reflect God's love!" to guide employees' actions. The hospital expanded its position descriptions to include the facility's expectations for employee behavior that is consistent with the mission. An orientation program for new employees emphasizes incorporating the mission concepts of courtesy and compassion into all activities. To establish the mission firmly as part of the corporate culture, the hospital established three recognition programs and redesigned its pay plan to recognize performance that reflects the hospital's mission. Redecorating the drab facility has improved employees' attitudes toward their work environment. Five years into the change process, the hospital now has clear direction for strategic decisions, a more cooperative atmosphere, and increased admissions. The process continues, and assessment of the mission establishment process will lead to the initiation of continuous quality improvement concepts.

Community defibrillation in the Scottish Highlands.

Prompt defibrillation after cardiac arrest is necessary to save life. Inexpensive systems providing defibrillation facilities in the community of the Highlands have been devised, one for Inverness town practices, and one for rural practices. Both systems work by 'blind' defibrillation, once the clinical diagnosis of cardiac arrest is confirmed. Acute anti-arrhythmic drugs and intravenous infusions were not available. The systems functioned satisfactorily with general acceptance by the general practices concerned.