Realities and enigmas of human viral influenza: pathogenesis,epidemiology and control

Influenza A is a viral disease of global dimension, presenting with high morbidity and mortality in annual epidemics, and in pandemics which are of infrequent occurrence but which have very high attack rates. Influenza probes reveal a continuing battle for survival between host and parasite in which the host population updates the specificity of its pool of humoral immunity by contact with and response to infection with the most recent viruses which possess altered antigenic specificity in their hemagglutinin (HA) ligand. HA ligand binds the virus to the cell to bring about infection. Viral survival relies on escape from host immunity through antigenic alterations in nature which arise through genetic drift by point mutation principally of the HA gene, or through genetic shift by reassortment exchange of the HA ligand with that of viruses retained in avian species. Partial control of influenza is by use of killed whole, subunit, or possible live virus vaccines, all of which rely on worldwide surveillance to provide early detection of the altered immunologic specificity of the next virus to come. Future global surveillance may be aided by studies of sampled viral isolates in laboratories having capabilities for accelerated genetic sequencing and for automated rapid throughput analyses as well. Influenza vaccines of the future must be directed toward use of conserved group-specific viral antigens, such as are present in transitional proteins which are exposed during the fusion of virus to the host cell. Chemotherapy, though still primordial, must eventually provide the ultimate solution to vaccine failures. Probing the enigma of the severe influenza pandemic of 1918-1919 is an exciting contemporary venture in which genetic reconstruction of the viral genome from surviving archival RNA is being conducted with great success. Present evidence reveals successive recycling in pandemics, of only 3 of the 15 possible avian viral HAs. Pandemics are believed, conventionally, to be derived solely by rare events in which wild viruses of man acquire a new HA ligand of avian origin. There might be an alternative possibility involving a periodicity in selective control by the host population itself, in its receptivity or rejection at a particular time of particular reassortant viruses which might be created more frequently in nature than we are presently aware. This hypothesis, though remote, provides a different way to view and to probe the enigma of pandemic influenza.     

Reteplase

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based) rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.     

Double blind, placebo controlled study of nedocromil sodium in asthma

After a two week baseline, 209 asthmatic children (mean age 10 years, range 6-17) were randomly allocated to receive 4 mg nedocromil sodium (n = 110) or placebo (n = 99) four times daily for 12 weeks in addition to their current treatment. The children completed daily diary cards and visited the clinic at four week intervals. Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores, pulmonary function and inhaled beta 2 bronchodilator use. Total symptom score decreased by 50% from baseline in the nedocromil sodium group and by 9% in the placebo group during the final four weeks. Nedocromil sodium was considered very or moderately effective by 78% of children/parents (placebo 59%) and 73% of clinicians (placebo 50%). Nausea, headache and sleepiness, and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments, respectively. Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment. It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children.     

Advances in the treatment of congestive heart failure: new approaches for an old disease

Heart failure is a symptom complex of varied etiology associated with substantial mortality. Approximately 5 million Americans have the disease, with 400,000 new cases diagnosed each year. Despite better understanding of its pathophysiology, therapeutic options remain suboptimal and the syndrome remains associated with high rates of hospitalization and loss of economic productivity. Management traditionally included vasodilators, diuretics, and digoxin, with a focus on controlling symptoms and improving ejection fraction and exercise capacity. Drug therapy now is focused on improving survival, with a reduction in health care costs related to hospitalizations. Drugs with a proven benefit in reducing morbidity and mortality are angiotensin-converting enzyme inhibitors, beta-blockers, and the combination of hydralazine plus a nitrate. Diuretics, digoxin, dihydropyridine calcium channel blockers, phosphodiesterase inhibitors, catecholamine infusions, amiodarone, left ventricular assist devices, and transplantation are also options.     

Impact of pharmacy counseling on compliance and effectiveness of combination lipid-lowering therapy in patients undergoing coronary artery revascularization: a randomized, controlled trial

This randomized, controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years. A random sample of 30 patients 7-30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl. All patients received lovastatin 20 mg/day and colestipol 5 g twice/day. Weekly telephone contact was made with each patient for 12 weeks. Short- and long-term compliance was assessed by pill and packet counts and refill records. Compliance and lipid profile results were significantly better in the intervention group (p<0.05) up to 2 years after the start of therapy than in the control group for all parameters except high-density lipoprotein. However, this effect was not apparent during the first 12 weeks of therapy. Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy.