Pediatric acute pain management.

The past decade has brought about an explosion of knowledge about the physiology of nociception and many new techniques for pain relief, new analgesic drugs, and new applications of old analgesic drugs. These techniques include methods of opioid administration by transdermal and transmucosal absorption and the use of neuraxial analgesia for the management of pain in children. Interest in the use of regional anesthesia in children has been rekindled, and analgesic properties and pre-emptive analgesic properties of many agents not typically considered analgesics, such as clonidine and ketamine, have been recognized. Perhaps the greatest advance has been the paradigm shift in the recognition that pain not only exists in infants and children but also is a significant cause of morbidity and even mortality. Given the unprecedented interest in pain management in adults and children, physicians can now look forward to the development of new methods of drug delivery and of receptor-specific drugs that divorce analgesia from the untoward side effects of existing analgesics. Improvement in the quality of life of hospitalized children also will occur.

Pain and symptom control in terminally ill children.

The management of pain in terminally ill pediatric patients has incalculable benefits to patients, their families, and physicians and nurses. A therapeutic management plan is dependent on a thorough understanding of the causes of pain in these patients, on pain assessment, and on the myriad drugs and drug strategies that are essential in pain treatment. Aggressive symptom control of treatment-related side effects can ensure successful implementation of such a plan.

Pain management for special populations-pediatric, geriatric, and intensive care unit patients.

The treatment of pain in children, the elderly, and intensive care unit patients presents some unique problems. Here a unifying theme is emphasized: the difficulty in adequately assessing pain in patients who are often unable to communicate. Also addressed are the differences in pharmacokinetics and pharmacodynamics from neonates to the elderly. Finally, common pain syndromes in each group, the associated treatments, and recent controversies are discussed. Because of changing demographics, pain treatment for these groups will become increasingly important. Only in the past 10 years has pediatric pain been treated with the same energy as adult pain; application of the newest techniques still lags far behind these patients' adult counterparts. Pain treatment in the elderly will inevitably become a larger problem as our population ages. Finally, recent advances in technology enable us to sustain patients with increasingly severe illnesses. Thus, pain management in these special populations will take on progressively greater importance.

Experimental ocular herpetic infections in rabbits. Treatment with 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine.

A new acyclic nucleoside, 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine (BIOLF-62), was found to be efficacious in the treatment of experimental ocular herpes simplex virus infections in rabbits. Complete healing of herpetic lesions occurred in a majority of animals after six days of topical treatment, three times per day. No toxic effects were observed in uninfected, drug-treated eyes. The BIOLF-62 treatment blocked viral replication in infected eyes sufficiently to make recovery of virus from any of the drug-treated eyes impossible, whereas virus was recovered from all placebo-treated eyes.

Sensitivity of equine herpesviruses 1 and 3 in vitro to a new nucleoside analogue, 9-[[2-hydroxy-1-(hydroxymethyl) ethoxy] methyl] guanine.

The following members of the Herpetoviridae family were tested to determine their sensitivities to the new antiviral drug, BIOLF-62: equine herpesvirus types 1 and 3, human herpesvirus types 1 and 2, swine herpesvirus, bovine herpesvirus type 4, feline herpesvirus, canine herpesvirus, and herpes simiae virus. Equine herpesviruses 1 and 3, human herpesviruses 1 and 2, and herpes simiae virus were all sensitive to BIOLF-62 at concentrations of less than 0.55 micrograms/ml. Equine herpesvirus types 1 and 3 were particularly sensitive, viral median effective dose (ED50) concentrations of the drug being only 0.033 and 0.16 micrograms/ml, respectively. Such high antiviral potency and low cell toxicity indicate that BIOLF-62 might be useful in the treatment of infected animals.

Synergism among BIOLF-62, phosphonoformate, and other antiherpetic compounds.

9-[[2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (BIOLF-62) is highly synergistic with either phosphonoformate or phosphonoacetate when used in combination against herpes simplex virus types 1 and 2 in vitro. Acycloguanosine did not show significant synergism with these two compounds. Bromovinyldeoxyuridine and phosphonoformate were highly synergistic against herpes simplex virus type 2, but not against type 1.

A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2.

A novel nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-guanine (BIOLF-62), was found to have potent antiviral activity against herpes simplex virus types 1 and 2 at concentrations well below cytotoxic levels. For example, the Patton strain of herpes simplex virus type 1 was susceptible at concentrations 140- to 2,900-fold below that which inhibited cell division by 50%, depending upon the cell line used for assay. Different herpesvirus strains varied considerably in their susceptibility to the drug, as did results obtained with the same virus strain in different cell lines. BIOLF-62 compared favorably with 5-iodo-2'-deoxyuridine and acyclovir with respect to ratios of viral to cell inhibitory drug concentrations. Patterns of drug resistance to herpesvirus mutants suggested that the primary mode of action of BIOLF-62 is different from that of known antiviral compounds. Human adenovirus type 2, varicella-zoster virus, and Epstein-Barr virus were inhibited by this drug but at concentrations within the cell inhibitory range. Vaccinia virus and human cytomegalovirus were not inhibited at high drug concentrations.