Richard J Whitley

Publications (64)628.31 Total impact

• Article: Oseltamivir Pharmacokinetics, Dosing, and Resistance in Children From Birth to Two Years of Age with Influenza.

  David W Kimberlin, Edward P Acosta, Mark N Prichard, Pablo J Sánchez, Krow Ampofo, David Lang, Negar Ashouri, John A Vanchiere, Mark J Abzug, Nazha Abughali, [......], Sunil K Sood, Michael G Spigarelli, John S Bradley, Judy Lew, Marian G Michaels, Wen Wan, Gretchen Cloud, Penelope Jester, Fred D Lakeman, Richard J Whitley
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  ABSTRACT: Background. Children under 2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children under 2 years of age is unknown.Methods. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants from birth to 2 years of age in an age-deescalation, adaptive design with a targeted systemic exposure.Results. From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0 through 8 months of age, although there was a greater degree of variability in infants under 3 months of age. In subjects 9 through 11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of ten subjects 12 through 23 months of age receiving the FDA-approved unit dose for this age group of 30 mg had oseltamivir carboxylate exposures below the target range. Virus from three subjects developed oseltamivir resistance during antiviral treatment.Conclusions. The appropriate twice-daily oral oseltamivir dose for infants birth through 8 months of age is 3.0 mg/kg, while the dose for infants 9 through 11 months is 3.5 mg/kg.
  The Journal of Infectious Diseases 12/2012; · 6.41 Impact Factor
• Article: Preclinical evaluation of a genetically engineered herpes simplex virus expressing interleukin-12.

  James M Markert, James J Cody, Jacqueline N Parker, Jennifer M Coleman, Kathleen H Price, Earl R Kern, Debra C Quenelle, Alfred D Lakeman, Trenton R Schoeb, Cheryl A Palmer, Samuel C Cartner, G Yancey Gillespie, Richard J Whitley
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  ABSTRACT: Herpes simplex virus 1 (HSV-1) mutants that lack the γ(1)34.5 gene are unable to replicate in the central nervous system but maintain replication competence in dividing cell populations, such as those found in brain tumors. We have previously demonstrated that a γ(1)34.5-deleted HSV-1 expressing murine interleukin-12 (IL-12; M002) prolonged survival of immunocompetent mice in intracranial models of brain tumors. We hypothesized that M002 would be suitable for use in clinical trials for patients with malignant glioma. To test this hypothesis, we (i) compared the efficacy of M002 to three other HSV-1 mutants, R3659, R8306, and G207, in murine models of brain tumors, (ii) examined the safety and biodistribution of M002 in the HSV-1-sensitive primate Aotus nancymae following intracerebral inoculation, and (iii) determined whether murine IL-12 produced by M002 was capable of activating primate lymphocytes. Results are summarized as follows: (i) M002 demonstrated superior antitumor activity in two different murine brain tumor models compared to three other genetically engineered HSV-1 mutants; (ii) no significant clinical or magnetic resonance imaging evidence of toxicity was observed following direct inoculation of M002 into the right frontal lobes of A. nancymae; (iii) there was no histopathologic evidence of disease in A. nancymae 1 month or 5.5 years following direct inoculation; and (iv) murine IL-12 produced by M002 activates A. nancymae lymphocytes in vitro. We conclude that the safety and preclinical efficacy of M002 warrants the advancement of a Δγ(1)34.5 virus expressing IL-12 to phase I clinical trials for patients with recurrent malignant glioma.
  Journal of Virology 02/2012; 86(9):5304-13. · 5.40 Impact Factor
• Article: Oral acyclovir suppression and neurodevelopment after neonatal herpes.

  David W Kimberlin, Richard J Whitley, Wen Wan, Dwight A Powell, Gregory Storch, Amina Ahmed, April Palmer, Pablo J Sánchez, Richard F Jacobs, John S Bradley, [......], Leonard B Weiner, Judith Guzman-Cottrill, Carol A McCarthy, Jill Griffin, Penelope Jester, Misty Parker, Fred D Lakeman, Huichien Kuo, Choo Hyung Lee, Gretchen A Cloud
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  ABSTRACT: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09). Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).
  New England Journal of Medicine 10/2011; 365(14):1284-92. · 53.30 Impact Factor
• Article: Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis.

  James E McJunkin, Milap C Nahata, Emily C De Los Reyes, W Garrett Hunt, Manuel Caceres, Raheel R Khan, Mouna G Chebib, Sasidharan Taravath, Linda L Minnich, Roxane Carr, Christine A Welch, Richard J Whitley
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  ABSTRACT: La Crosse viral encephalitis (LACVE) is associated with residual epilepsy and neurocognitive deficits in survivors. This report summarizes 3 phases of clinical studies of children treated with intravenous (IV) ribavirin (RBV), each one exploring a different phase (I, IIA, IIB) of clinical trial development. In phase I, 7 children with life-threatening LACVE were treated with emergency use RBV using a moderate IV dose (8.33 mg/kg/dose q 8 hours day 1, 5 mg/kg/dose q 8 hours days 2-10). In phase IIA, 12 children with severe LACVE were enrolled: 8 treated with RBV (same dose as phase I) and 4 with placebo. In phase IIB an escalated dose was used (33 mg/kg dose 1, then 16 mg/kg/dose q 6 hours for 4 days, and 8 mg/kg/dose q 8 hours for 3 days). In a group of 15 children treated in phase I and phase IIA, RBV appeared safe at moderate dose, but based on steady-state RBV levels of 9.3 μM, estimated cerebrospinal fluid levels were less than 20% of the EC50 of RBV for LACVE. At the escalated dose used in phase IIB, adverse events occurred, likely related to RBV, and therefore the trial was discontinued. Nevertheless, valuable pharmacokinetic (PK) and safety data were obtained at moderate dose, with potential treatment implications for other indications. Although the results do not support the use of RBV for LACVE, this nevertheless is the largest study of antiviral treatment for LACVE to date and the largest pharmacokinetic analysis of IV RBV in children for any indication.
  The Pediatric Infectious Disease Journal 05/2011; 30(10):860-5. · 3.58 Impact Factor
• Article: The Alabama Drug Discovery Alliance: a collaborative partnership to facilitate academic drug discovery.

  Maaike Everts, W Blaine Knight, David R Harris, John A Secrist, Richard J Whitley
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  ABSTRACT: The Alabama Drug Discovery Alliance is a collaboration between the University of Alabama at Birmingham and Southern Research Institute that aims to support the discovery and development of therapeutic molecules that address an unmet medical need. The alliance builds on the expertise present at both institutions and has the dedicated commitment of their respective technology transfer and intellectual property offices to guide any commercial opportunities that may arise from the supported efforts. Although most projects involve high throughput screening, projects at any stage in the drug discovery and development pathway are eligible for support. Irrespective of the target and stage of any project, well-functioning interdisciplinary teams are crucial to a project's progress. These teams consist of investigators with a wide variety of expertise from both institutions to contribute to the program's success.
  Pharmaceutical Research 03/2011; 28(7):1454-9. · 4.09 Impact Factor
• Article: Oseltamivir dosing for influenza infection in premature neonates.

  Edward P Acosta, Penelope Jester, Peter Gal, John Wimmer, Joni Wade, Richard J Whitley, David W Kimberlin
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  ABSTRACT: Under the Emergency Use Authorization issued in April 2009, oseltamivir can be used to treat 2009 influenza A (H1N1) virus infection in children aged <1 year. No data exist on the dosing of oseltamivir in premature babies. A hospital health care worker inadvertently exposed 32 neonatal intensive care unit babies to 2009 influenza A (H1N1); a protocol was expeditiously implemented to collect samples for pharmacokinetics and dosage evaluation. Results suggest 1.0 mg/kg/dose twice daily in premature babies produces oseltamivir carboxylate exposures similar to that in older children receiving 3.0 mg/kg/dose twice daily. These results provide initial guidance on dosing oseltamivir in this vulnerable population.
  The Journal of Infectious Diseases 08/2010; 202(4):563-6. · 6.41 Impact Factor
• Source

  Available from: Antonio Volpi

  Article: Management of herpes zoster and post-herpetic neuralgia now and in the future.

  Richard J Whitley, Antonio Volpi, Mike McKendrick, Albert van Wijck, Anne Louise Oaklander
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  ABSTRACT: Herpes zoster (HZ; shingles)--a reactivation of the latent varicella zoster virus (VZV)--can cause significant morbidity. Its major complication is pain, particularly post-herpetic neuralgia (PHN). We will review the current management strategies available for the treatment of both acute HZ and PHN, including antiviral drugs, analgesic agents, anticonvulsants, tricyclic antidepressants and topical therapies. New molecules in development that show improved activity against VZV are also covered, and new drug targets are outlined. The role of translational neuroscience in moving towards a goal of finding disease-modifying treatments will be examined.
  Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 05/2010; 48 Suppl 1:S20-8. · 3.12 Impact Factor
• Article: Safety of Oseltamivir Compared With the Adamantanes in Children Less Than 12 Months of Age

  David W. Kimberlin, Marwan Shalabi, Mark J. Abzug, David Lang, Richard F. Jacobs, Gregory Storch, John S. Bradley, Kelly C. Wade, Octavio Ramilo, José R. Romero, [......], Charles Leach, Judith Guzman-Cottrill, Joan Robinson, Nazha Abughali, Janet Englund, Jill Griffin, Penny Jester, Gretchen A. Cloud, Richard J. Whitley, and the NIAID Collaborative Antiviral Study Group
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  ABSTRACT: Background: When oseltamivir is administered in extremely high doses (500–1000 mg/kg) to young juvenile rats, central nervous system toxicity and death occurred in some animals. Mortality was not observed in older juvenile rats, suggesting a possible relationship between neurotoxicity and an immature blood-brain barrier. To assess potential neurologic adverse effects of oseltamivir use in infants, a retrospective chart review was performed in infants less than 12 months of age who received oseltamivir, amantadine, or rimantadine. Methods: The primary objective was to describe the frequency of neurologic adverse events among children less than 12 months of age who received oseltamivir compared with those receiving adamantanes. Medical record databases, emergency department databases, and/or pharmacy records at 15 medical centers were searched to identify patients. Results: Of the 180 infants identified as having received antiviral therapy, 115 (64%) received oseltamivir, 37 (20%) received amantadine, and 28 (16%) received rimantadine. The median dose of oseltamivir was 2.0 mg/kg/dose in 3- to 5-month-old and 2.2 mg/kg/dose in 9- to 12-month-old infants. The maximum dose administered was 7.0 mg/kg/dose. There were no statistically significant differences in the occurrence of adverse neurologic events during therapy among subjects treated with oseltamivir versus those treated with the adamantanes (P = 0.13). Conclusions: This is the largest report to date of oseltamivir use in children less than 12 months of age. Neurologic events were not more common with use of oseltamivir compared with that of the adamantanes. Dosing of oseltamivir was variable, illustrating the need for pharmacokinetic data in this younger population.
  The Pediatric Infectious Disease Journal 02/2010; 29(3):195-198. · 3.58 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Of ferrets and humans: influenza pathogenesis.

  Richard J Whitley
  The Journal of Infectious Diseases 02/2010; 201(7):976-7. · 6.41 Impact Factor
• Article: Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system.

  Sara E Oliver, Gretchen A Cloud, Pablo J Sánchez, Gail J Demmler, Wayne Dankner, Mark Shelton, Richard F Jacobs, Wendy Vaudry, Robert F Pass, Seng-jaw Soong, Richard J Whitley, David W Kimberlin
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  ABSTRACT: Ganciclovir protects against hearing deterioration in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS). To assess the neurodevelopmental impact of ganciclovir therapy in this population. 100 neonates were enrolled into a controlled Phase III study of symptomatic congenital CMV involving the CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no treatment. Denver developmental tests were performed at 6 weeks, 6 months, and 12 months. For each age, developmental milestones that > or =90% of normal children would be expected to have achieved were identified. The numbers of milestones not met ("delays") were determined for each subject. The average number of delays per subject was compared for each treatment group. At 6 months, the average number of delays was 4.46 and 7.51, respectively, for ganciclovir recipients and "no treatment" subjects (p=0.02). At 12 months, the average number of delays was 10.06 and 17.14, respectively (p=0.007). In a multivariate regression model, the effect of ganciclovir therapy remained statistically significant at 12 months (p=0.007). Infants with symptomatic congenital CMV involving the CNS receiving intravenous ganciclovir therapy have fewer developmental delays at 6 and 12 months compared with untreated infants. Based on these data as well as the previously published data regarding ganciclovir treatment and hearing outcomes, 6 weeks of intravenous ganciclovir therapy can be considered in the management of babies with symptomatic congenital CMV disease involving the CNS. If treatment is initiated, it should be started within the first month of life and patients should be monitored closely for toxicity, especially neutropenia. Since existing data only address the treatment of symptomatic congenital CMV disease involving the CNS, these data cannot be extrapolated to neonates with other manifestations of CMV disease, including asymptomatic babies and symptomatic babies who do not have CNS involvement.
  Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 09/2009; 46 Suppl 4:S22-6. · 3.12 Impact Factor
• Article: Inhibition of herpesvirus replication by 5-substituted 4'-thiopyrimidine nucleosides.

  Mark N Prichard, Debra C Quenelle, Caroll B Hartline, Emma A Harden, Geraldine Jefferson, Samuel L Frederick, Shannon L Daily, Richard J Whitley, Kamal N Tiwari, Joseph A Maddry, John A Secrist, Earl R Kern
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  ABSTRACT: A series of 4'-thionucleosides were synthesized and evaluated for activities against orthopoxviruses and herpesviruses. We reported previously that one analog, 5-iodo-4'-thio-2'-deoxyuridine (4'-thioIDU), exhibits good activity both in vitro and in vivo against two orthopoxviruses. This compound also has good activity in cell culture against many of the herpesviruses. It inhibited the replication of herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus with 50% effective concentrations (EC(50)s) of 0.1, 0.5, and 2 microM, respectively. It also inhibited the replication of human cytomegalovirus (HCMV) with an EC(50) of 5.9 microM but did not selectively inhibit Epstein-Barr virus, human herpesvirus 6, or human herpesvirus 8. While acyclovir-resistant strains of HSV-1 and HSV-2 were comparatively resistant to 4'-thioIDU, it retained modest activity (EC(50)s of 4 to 12 microM) against these strains. Some ganciclovir-resistant strains of HCMV also exhibited reduced susceptibilities to the compound, which appeared to be related to the specific mutations in the DNA polymerase, consistent with the observed incorporation of the compound into viral DNA. The activity of 4'-thioIDU was also evaluated using mice infected intranasally with the MS strain of HSV-2. Although there was no decrease in final mortality rates, the mean length of survival after inoculation increased significantly (P < 0.05) for all animals receiving 4'-thioIDU. The findings from the studies presented here suggest that 4'-thioIDU is a good inhibitor of some herpesviruses, as well as orthopoxviruses, and this class of compounds warrants further study as a therapy for infections with these viruses.
  Antimicrobial Agents and Chemotherapy 09/2009; 53(12):5251-8. · 4.84 Impact Factor
• Article: Antiviral therapy for herpesvirus central nervous system infections: neonatal herpes simplex virus infection, herpes simplex encephalitis, and congenital cytomegalovirus infection.

  Scott H James, David W Kimberlin, Richard J Whitley
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  ABSTRACT: Herpesvirus infections of the central nervous system (CNS) are a significant cause of morbidity and mortality, including long-term neurologic sequelae. Among the family of herpesviruses, the most significant CNS infections are due to herpes simplex virus (HSV) and cytomegalovirus (CMV). The onset of HSV CNS infection can occur in neonates as well as older children and adults. CNS infection associated with CMV occurs predominantly in the perinatal period, but may also be seen rarely in children and adults, especially in immunocompromised individuals. Although advances in antiviral agents have led to improved outcomes, there is still a need for more effective treatments.
  Antiviral research 06/2009; 83(3):207-13. · 3.61 Impact Factor
• Article: Herpes zoster in the age of focused immunosuppressive therapy.

  Richard J Whitley, John W Gnann
  JAMA The Journal of the American Medical Association 03/2009; 301(7):774-5. · 30.03 Impact Factor
• Source

  Available from: Michael Ison

  Article: Detection and diagnosis of herpes simplex virus infection in adults with acute liver failure.

  Josh Levitsky, Anupama T Duddempudi, Fred D Lakeman, Richard J Whitley, James P Luby, William M Lee, Robert J Fontana, Andres T Blei, Michael G Ison
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  ABSTRACT: Disseminated herpes simplex virus (HSV) infection may lead to acute liver failure (ALF) and the need for emergency liver transplantation (LT). The primary aim of this study was to determine the utility of HSV serological testing and HSV DNA testing by polymerase chain reaction (PCR) in the diagnosis and management of indeterminate, pregnancy-related, and known HSV-related ALF. Stored sera obtained on study day 1 or 2 from patients enrolled in the United States ALF Study Group with indeterminate (n = 51), pregnancy-related (n = 12), and HSV-related (n = 4) ALF were screened for HSV DNA by PCR and serology. While 7 of the indeterminate and pregnant patients had positive anti-HSV immunoglobulin M, none had detectable HSV DNA. The 4 known HSV cases all had high-titer HSV DNA on presentation (range: 3.5 to 36 x 10(8) copies/mL). Two HSV patients underwent LT but developed posttransplant extrahepatic HSV infection despite suppression of HSV DNA with acyclovir treatment, and one of them eventually died. The 2 other fulminant HSV patients died within 48 hours of presentation. In conclusion, serum HSV DNA indicative of occult HSV infection was not detected in 51 indeterminate and 12 pregnancy-related ALF patients. The 4 patients with known HSV-related ALF all had high HSV DNA levels at presentation, and despite the rapid use of antiviral therapy and emergency LT, substantial morbidity and mortality were encountered, highlighting the poor prognosis with severe disseminated HSV infection.
  Liver Transplantation 11/2008; 14(10):1498-504. · 3.39 Impact Factor
• Article: Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM.

  James M Markert, Peter G Liechty, Wenquan Wang, Shanna Gaston, Eunice Braz, Matthias Karrasch, Louis B Nabors, Michael Markiewicz, Alfred D Lakeman, Cheryl A Palmer, Jacqueline N Parker, Richard J Whitley, George Y Gillespie
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  ABSTRACT: We have previously demonstrated safety of G207, a doubly mutated (deletion of both gamma(1)34.5 loci, insertional inactivation of U(L)39) herpes simplex virus (HSV) for patients stereotactically inoculated in enhancing portions of recurrent malignant gliomas. We have now determined safety of two inoculations of G207, before and after tumor resection. Inclusion criteria were histologically proven recurrent malignant glioma, Karnofsky score >or=70, and ability to resect the tumor without ventricular system breach. Patients received two doses of G207 totaling 1.15 x 10(9) plaque-forming units with 13% of this total injected via a catheter placed stereotactically in the tumor. Two or five days later, tumor was resected en bloc with catheter in place. The balance of G207 dose was injected into brain surrounding the resection cavity. Six patients with recurrent glioblastoma multiforme were enrolled. Two days after the second G207 inoculation, one patient experienced transient fever, delirium, and hemiparesis, which entirely resolved on high-dose dexamethasone. No patient developed HSV encephalitis or required treatment with acyclovir. Radiographic and neuropathologic evidence suggestive of antitumor activity is reported. Evidence of viral replication was demonstrated. G207 appears safe for multiple dose delivery, including direct inoculation into the brain surrounding tumor resection cavity.
  Molecular Therapy 10/2008; 17(1):199-207. · 6.87 Impact Factor
• Article: Seasonal and pandemic influenza: a 2007 update on challenges and solutions.

  Arnold S Monto, Richard J Whitley
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  ABSTRACT: The second annual Seasonal and Pandemic Influenza Conference, which took place in February 2007 in Arlington, Virginia, focused on recent progress in basic and clinical research regarding preparedness for outbreaks of influenza. Sporadic outbreaks of avian influenza A in Asia and the Middle East remind us that the threat of another influenza pandemic remains real. Although the exact mechanisms underlying avian influenza A human pathogenicity remain unclear, preclinical studies in animal models provide insights into the mechanisms of avian influenza A virus infection and transmission from bird to human and, rarely, from human to human. With regard to prevention, developmental studies of adjuvant-supplemented vaccines indicate promising immunogenicity and cross-reactivity. The pipeline of new antiviral agents in development is also increasing, including a new neuraminidase inhibitor and agents aimed at completely new targets. Global strategic planning efforts focus on assuring sufficient stocks of vaccines and antiviral agents, as well as timely nonpharmacological interventions to potentially delay or contain spread of an outbreak. These initiatives will also help control outbreaks of seasonal influenza.
  Clinical Infectious Diseases 05/2008; 46(7):1024-31. · 9.15 Impact Factor
• Article: Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease.

  David W Kimberlin, Edward P Acosta, Pablo J Sánchez, Sunil Sood, Vish Agrawal, James Homans, Richard F Jacobs, David Lang, Jose R Romero, Jill Griffin, Gretchen A Cloud, Fred D Lakeman, Richard J Whitley
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  ABSTRACT: Intravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system. Twenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration of valganciclovir oral solution and of intravenous ganciclovir. On the basis of a previous pharmacokinetic study of the use of intravenous ganciclovir in this population, a target AUC12 (area under the concentration-time curve over a 12-h period) of 27 mg x h/L was defined. The median dose of oral valganciclovir administered in the present trial was 16 mg/kg, which produced a geometric mean AUC12 of 27.4 mg x h/L. The bioavailability of valganciclovir was 41.1%. Of the 18 subjects who had detectable CMV in whole blood at baseline or during therapy, 11 had <4 log viral DNA copies/mL at baseline, and 7 had > or =4 log viral DNA copies/mL at baseline; subjects who started the study with the higher viral burden experienced greater decreases in viral load but did not clear virus during the 42-day course of therapy. Neutropenia of grade 3 or 4 developed in 38% of subjects. In neonates with symptomatic congenital CMV disease, valganciclovir oral solution provides plasma concentrations of ganciclovir comparable to those achieved with administration of intravenous ganciclovir. The results of the present study cannot be extrapolated to extemporaneously compounded liquid formulations of valganciclovir.
  The Journal of Infectious Diseases 03/2008; 197(6):836-45. · 6.41 Impact Factor
• Article: Therapy of herpes virus infections in children.

  Richard J Whitley
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  ABSTRACT: Significant progress has been made in the treatment of viral infections in children, particularly those caused by HSV, varicella-zoster virus and cytomegalovirus. While not discussed in this review, licensed therapies are available for influenza infection in children as well. However, and notably so, numerous viral diseases of children represent unmet medical needs and warrant dedicated drug discovery efforts, including hepatitis B and C, and respiratory syncytial virus, among others.
  Advances in experimental medicine and biology 02/2008; 609:216-32. · 1.09 Impact Factor
• Source

  Available from: rsds.org

  Article: Diagnosis and assessment of pain associated with herpes zoster and postherpetic neuralgia.

  Robert H Dworkin, John W Gnann, Anne Louise Oaklander, Srinivasa N Raja, Kenneth E Schmader, Richard J Whitley
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  ABSTRACT: Accurate evaluation of pain plays a critical role in identifying new interventions for the treatment and prevention of herpes zoster and postherpetic neuralgia (PHN). Different types of pain and other sensory symptoms are found in patients with herpes zoster, and these vary greatly with respect to their presence, location, duration, intensity, and quality. The results of recent studies of herpes zoster and PHN and the development of new methods for assessing neuropathic pain provide a foundation for diagnosing and assessing the pain associated with herpes zoster. We review the results of recent research to identify the essential components that must be considered in developing an evidence-based description of pain associated with herpes zoster and PHN. PERSPECTIVE: Comprehensive assessments of pain are necessary for clinical research on the epidemiology, natural history, pathophysiologic mechanisms, treatment, and prevention of pain in herpes zoster and PHN.
  Journal of Pain 02/2008; 9(1 Suppl 1):S37-44. · 4.93 Impact Factor
• Article: The incidence and severity of herpes simplex encephalitis in Sweden, 1990-2001.

  Richard J Whitley, John W Gnann
  Clinical Infectious Diseases 11/2007; 45(7):881-2. · 9.15 Impact Factor