1: Antimicrob Agents Chemother. 2009 Mar 9. [Epub ahead of print] Pharmacokinetics and Safety of Famciclovir in Children with Herpes Simplex or Varicella Zoster Virus Infection. Saez-Llorens X, Yogev R, Arguedas A, Rodriguez A, Spigarelli MG, De Leon Castrejon T, Bomgaars L, Roberts M, Abrams B, Zhou W, Looby M, Kaiser G, Hamed K. Hospital del Nino, Panama City, Panama; Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60614; Instituto de Atencion Pediatrica, and Universidad de Ciencias Medicas, San Jose, Costa Rica; Hospital Infantil de Infectologia y Rehabilitacion, Guatemala City, Guatemala; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229; Hospital Materno Infantil Jose Domingo de Obaldia, Chiriqui, Panama; Texas Children's Hospital, Houston, Texas 77030; Novartis, East Hanover, New Jersey 07936; Novartis Pharma AG, Basel - CH 4002, Switzerland. Two multicenter, open-label, single-arm, two-phase studies, evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection. Pooled pharmacokinetic data were generated following single doses in 51 participants ( approximately 12.5 mg/kg for children <40 kg and 500 mg for children >/=40 kg). Average systemic exposure to penciclovir was similar (6 to 12 year-olds) or slightly lower (1 to <6 year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). Apparent clearance of penciclovir increased with body weight (BW) in a non-linear manner, proportional to BW(0.696). An 8-step weight-based dosing regimen was developed to optimize exposure in smaller children, and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV patients who received famciclovir bid and 24 of 53 (45.3%) VZV patients who received famciclovir tid experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet(R)) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves similar systemic exposures to the 500-mg dose in adults. PMID: 19273678 [PubMed - as supplied by publisher] 2: Ann Acad Med Singapore. 2009 Feb;38(2):136-8. Herpes zoster as a useful clinical marker of underlying cell-mediated immune disorders. Soyuncu S, Berk Y, Eken C, Gulen B, Oktay C. Department of Emergency Medicine, Akdeniz University Faculty of Medicine, 07059 Antalya, Turkey. ssoyuncu@akdeniz.edu.tr INTRODUCTION: The objective of this study was to determine the necessity of further evaluation of patients presented with herpes zoster (HZ) to the Emergency Department for the underlying decreased cell-mediated immunity. MATERIALS AND METHODS: The data of 132 adult patients presenting with HZ to the Emergency Department were collected from the computerised database of Akdeniz University Hospital. The following data were recorded: demographic data and underlying diseases during onset of HZ and laboratory results (white blood cell counts, blood glucose levels). RESULTS: There were 132 patients with HZ in the study period. The mean age of patients was 52.98 +/- 18.91 years (range, 14 to 96) and 53% (70 patients) were male. Of the study patients, 70.5% (93 patients) were over 45 years old. Eight (6.1%) patients had been diagnosed to have a malignancy, 18 (13.6%) had diabetes mellitus and 3 (2.3%) patients had undergone organ transplantation during their admission. Malignancy, diabetes mellitus and organ transplantation prevalence in the HZ group was significantly higher than the whole Emergency Department population. CONCLUSIONS: Our results indicate a relationship between the presence of HZ and increasing age and cell-mediated immunosuppressive disorders in Emergency Department patients over the age of 45 years. HZ should be considered as a clinical marker of cell-mediated immunosuppressive disorders, particularly in elderly patients. PMID: 19271041 [PubMed - in process] 3: BMJ. 2009 Mar 6;338:b944. doi: 10.1136/bmj.b944. Shingles vaccination is likely to be cost effective at age 65 or 70. Dobson R. Publication Types: News PMID: 19270023 [PubMed - in process] 4: J Clin Rheumatol. 2009 Mar;15(2):101. Comment on: J Clin Rheumatol. 2006 Oct;12(5):249-51. Herpes zoster infection followed by Henoch-Schonlein purpura in a girl receiving infliximab for ulcerative colitis. Nobile S, Catassi C, Felici L. Publication Types: Comment Letter PMID: 19265360 [PubMed - in process] 5: Auris Nasus Larynx. 2009 Mar 3. [Epub ahead of print] Herpes zoster laryngitis with intractable hiccups. Morinaka S. Department of Otorhinolaryngology, Kobe Japanpost Hospital, 6-2-43 Kamitsutsui-dori, Chuo-ku, 651-8798 Kobe, Japan. A 73-year-old man presented to our hospital with a sore throat (left-sided) and hiccups. The patient had mucosal swelling and erosions affecting the left posterior pillar, base of tongue, epiglottis, arytenoid, and aryepiglottic fold. As the laryngeal mucosal edema became worse, herpetic vesicles and erosions developed on the left cavum conchae, external auditory canal, and palate. The patient was treated with acyclovir and a steroid. His hiccups were treated with metoclopramide, but it had little effect, and hiccups only subsided gradually after the disappearance of erosions. His hiccups relapsed transiently with vomiting, and then resolved completely. Elevation of the CF titer after 2 weeks confirmed the diagnosis of herpes zoster. This condition should be considered in patients with unilateral sore throat and intractable hiccups, and treatment with acyclovir should be provided. PMID: 19264432 [PubMed - as supplied by publisher] 6: J Clin Microbiol. 2009 Mar 4. [Epub ahead of print] Multiplex PCR testing detected higher than expected rates of cervical Mycoplasmas, Ureaplasmas, Trichomonas and viral agents in sexually active Australian women. McIver CJ, Rismanto N, Smith C, Naing ZW, Rayner B, Lusk J, Konecny P, White PA, Rawlinson WD. Virology Division, Microbiology Department (SEALS), The Prince of Wales Hospital, School of Medical Sciences, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, RPA Sexual Health, Royal Prince Alfred Hospital, Department of Immunology and Infectious Diseases, St George Hospital, Sydney, Australia. Knowing the prevalence of potential aetiologic agents of non-gonococcal and non-chlamydial cervicitis is important for improving efficacy of empirical treatments for this commonly encountered condition. We describe four multiplex PCRs (mPCRs) designated VDL05, VDL06, VDL07 and VDL09, which facilitate the detection of a wide range of agents either known to be or putatively associated with cervicitis including: Cytomegalovirus (CMV), Enterovirus (EV), Epstein Barr Virus (EBV), Varicella Zoster virus (VZV), Herpes simplex virus -1 (HSV-1) and Herpes simplex -2 (HSV-2) (VDL05); Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma genitalium, Mycoplasma hominis (VDL06); Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, and group B streptococci (VDL07); and adenovirus species A-E (VDL09). The mPCRs were used to test 233 cervical swabs from 175 women attending a sexual health clinic in Sydney Australia, during 2006-2007. The agents detected alone or in combination in all cervical swabs (percentage total swabs) include: CMV (6.0), EV (2.1), EBV (2.6), VZV (4.7), HSV -1 (2.6), HSV -2 (0.8), HSV-2 and VZV (0.4), U. parvum (57.0), U. urealyticum (6.1), M. genitalium (1.3), M. hominis (13.7), C. trachomatis (0.4), T. vaginalis (3.4), and Group B streptococci (0.4). Adenovirus species A-E and T. pallidum were not detected. These assays are adaptable for routine diagnostic laboratories and provide an opportunity to measure the true prevalence of micro-organisms potentially associated with cervicitis and other genital infections. PMID: 19261782 [PubMed - as supplied by publisher] 7: Clin Vaccine Immunol. 2009 Mar 4. [Epub ahead of print] A Comparison of the Immunogenicity and Safety of ZOSTAVAX(R) in Adults 50 to 59 Years Old and Adults >=60 Years Old. Sutradhar SC, Wang WW, Schlienger K, Stek JE, Xu J, Chan IS, Silber JL. Merck Research Laboratories, Upper Gwynedd, PA. Background: ZOSTAVAX(R) has been shown to be efficacious in the prevention of herpes zoster (HZ), and generally well tolerated in clinical trials among subjects >/=60 years old. This prespecified combined analysis from 2 studies compares immunogenicity and safety of ZOSTAVAX(R) in subjects 50 to 59 years old versus those >/=60 years old. Methods: VZV Ab titers were measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) at baseline and 4 weeks postvaccination. Noninferiority was evaluated by estimated geometric mean fold rise (GMFR) ratio [50 to 59 years old/>/=60 years old] and 2-sided 95% confidence interval (CI). Success was defined by lower bound (LB) of 95% CI of GMFR ratio >0.67. Acceptability of postvaccination VZV Ab was defined by LB of 95% CI of GMFR >1.4. Safety data was recorded for 28 days postvaccination by standardized Vaccination Report Card. Results: Estimated GMFR from baseline to 4 weeks postvaccination was 2.6 (95% CI: 2.4, 2.9) in subjects 50 to 59 years old and 2.3 (95% CI: 2.1, 2.4) in subjects >/=60 years old. The estimated GMFR ratio [50 to 59 years old/>/=60 years old] was 1.13 (95% CI: 1.02, 1.25). No ZOSTAVAX(R)-related serious AEs were reported. Conclusions: After a dose of ZOSTAVAX(R), GMFR of VZV Ab response in subjects 50 to 59 years old was noninferior to that in subjects >/=60 years old. VZV Ab response was acceptable in both age groups. ZOSTAVAX(R) was generally well tolerated in both age groups. PMID: 19261769 [PubMed - as supplied by publisher] 8: Cleve Clin J Med. 2009 Mar;76(3):152; author reply 152. Comment on: Cleve Clin J Med. 2009 Jan;76(1):45-8. Shingles vaccine ((JANUARY 2009). Hirsch R. Publication Types: Comment Letter PMID: 19258459 [PubMed - in process] 9: Eur J Dermatol. 2009 Mar 2. [Epub ahead of print] Herpes zoster occurring as a solitary vesicular in malignant lymphoma. Ishida N, Watanabe D, Kuhara T, Takama H, Tamada Y, Matsumoto Y. PMID: 19258238 [PubMed - as supplied by publisher] 10: Mayo Clin Proc. 2009 Mar;84(3):274-80. Herpes zoster (shingles) and postherpetic neuralgia. Sampathkumar P, Drage LA, Martin DP. Division of Infectious Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. sampathkumar.priya@mayo.edu Herpes zoster (HZ), commonly called shingles, is a distinctive syndrome caused by reactivation of varicella zoster virus (VZV). This reactivation occurs when immunity to VZV declines because of aging or immunosuppression. Herpes zoster can occur at any age but most commonly affects the elderly population. Postherpetic neuralgia (PHN), defined as pain persisting more than 3 months after the rash has healed, is a debilitating and difficult to manage consequence of HZ. The diagnosis of HZ is usually made clinically on the basis of the characteristic appearance of the rash. Early recognition and treatment can reduce acute symptoms and may also reduce PHN. A live, attenuated vaccine aimed at boosting immunity to VZV and reducing the risk of HZ is now available and is recommended for adults older than 60 years. The vaccine has been shown to reduce significantly the incidence of both HZ and PHN. The vaccine is well tolerated, with minor local injection site reactions being the most common adverse event. This review focuses on the clinical manifestations and treatment of HZ and PHN, as well as the appropriate use of the HZ vaccine. PMID: 19252116 [PubMed - in process] 11: JAAPA. 2009 Jan;22(1):45-7. Hypertension; herpes zoster. Olsen ME, Klingler AM. Nephrology & Hypertension Associates, Middlebury, Connecticut, USA. PMID: 19248361 [PubMed - in process] 12: World J Gastroenterol. 2009 Feb 28;15(8):1004-6. Severe autoimmune hepatitis triggered by varicella zoster infection. Al-Hamoudi WK. Gastroenterology and Hepatology Unit (59), Department of Medicine, King Saud University, PO Box 2925, Riyadh 11461, Saudi Arabia. walhamoudi@gmail.com. Autoimmune hepatitis (AIH) is a chronic disease of unknown etiology that is characterized by the presence of circulatory autoantibodies and inflammatory histological changes in the liver. Although the pathogenesis of AIH is not known, it is thought that, in a genetically predisposed individual, environmental factors such as viruses can trigger the autoimmune process. Herpes simplex virus, Epstein-Barr virus, measles virus, and hepatitis viruses are thought to play a role in the etiology of AIH. Proteins belonging to these viruses may be similar to the amino acid chains of different autoantigens in the liver, this causes immune cross reactions and liver tissue damage. We report a case of severe AIH following varicella zoster infection in a 23-year-old man, and speculate that, based on the molecular mimicry hypothesis, the liver damage was caused by an immune cross reaction to the viral proteins. Varicella-zoster-induced AIH has not been reported previously. PMID: 19248202 [PubMed - in process] 13: Indian J Ophthalmol. 2009 Mar-Apr;57(2):163-4. Herpes zoster ophthalmicus or Herpes zoster maxillaris? Chandravanshi SL, Rathore MK. Department of Ophthalmology, S. S. Medical College and Gandhi Memorial Hospital Rewa, M.P - 486 001, India. dr_scl@rediffmail.com. Publication Types: Letter PMID: 19237800 [PubMed - in process] 14: Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Feb;17(1):214-7. [Bortezomib combined with other drugs for treating 60 cases of multiple myeloma.] [Article in Chinese] Zhong YP, Chen SL, Li X, Hu Y, Zhang JJ. Department of Hematology and Oncology, Beijing Chaoyuang Hospital, Capital Medical University, Beijing 100043, China. E-mail: zhongyp3352@126.com. The aim of this study was to investigate the efficacy and safety of bortezomib-combined with dexamethasone, methylprednisolone and other drugs in the treatment of patients with multiple myeloma (MM). 60 MM patients including 19 de novo patients, out of them 14 patients received the treatment using regimen of bortezomib in combination with thalidomide (BT), 5 patients received bortezomib-methylprednisolone regimen (BMP). Out of 41 patients with refractory or relapsed myeloma 26 cases of MM received the treatment using regimen of bortezovnib combirned with methylpreamsolone (BMP), 6 cases received the treatment using regimen of bortezomib combined with cyclophosphamide, predisone and thalidomide (BCPT), 5 cases received the treatment using regimen of bortezomib combined with cis-diaminodichloroplatimm, etoposide, cydophosphomide and dexame thecson (BDECD), 4 cases received the treatment using regimen of bortesomib combined with dexamethason (BD). Each patient received treatment of 2-8 courses at least. Response was assessed according to the criteria of the Blade. Adverse events were graded according to the commom Toxicity Criteria, version 3.0 (NCI CTCAE, USA). The median follow-up from the start of bortezomib treatment was 9 months. The results showed that out of 19 newly aiagnosed patients, 6 cares acheieved CR, 6 cases acheived nearly CR, 5 cases acheived PR, 1 case acheived MR, resulting in an ORR of 94.7%. Out of 41 refractory or relapsed patients, 5 cases acheieved CR, 10 cases got nearly CR, 14 cases were PR and 5 cases were MR, resuling in an ORR of 82.92%. The main toxicities were fatigue, gastrointestinal disorders, peripheral neuropathy, thrombocytopenia, herpes zoster, skinrash. All adverse events were diminished by using routine ways. In couclusion, bortezomib combined with orthe drugs is a very effective regimen, its side effects are predictable and manageable. Publication Types: English Abstract PMID: 19236782 [PubMed - in process] 15: Mol Pharmacol. 2009 Feb 20. [Epub ahead of print] Human Mitochondrial Thymidine Kinase (TK-2) is Selectively Inhibited by 3'-Thiourea Derivatives of {beta}-Thymidine. Identification of residues crucial for both inhibition and catalytic activity. Balzarini J, Van Daele I, Negri A, Solaroli N, Karlsson A, Liekens S, Gago F, Van Calenbergh S. Rega Institute for Medical Research. Substituted 3'-thiourea derivatives of beta-thymidine (dThd) and 5'-thiourea derivatives of alpha-dThd have been evaluated for their inhibitory activity against recombinant human cytosolic dThd kinase-1 (TK-1), human mitochondrial TK-2, herpes simplex virus type 1 (HSV-1) TK and varicella-zoster virus (VZV) TK. Several substituted 3'-thiourea derivatives of beta-dThd proved highly inhibitory to and selective for TK-2 (IC50: 0.15-3.1 microM). The 3'-C-branched p-methylphenyl (1) and 3-CF3-4-Cl-phenyl (7) thiourea derivatives of beta-dThd showed competitive inhibition of TK-2 when dThd was used as the variable substrate (Ki: 0.40 microM and 0.05 microM, respectively) but uncompetitive inhibition in the presence of variable concentrations of ATP (Ki: 15 microM and 2.0 microM, respectively). These kinetic properties of 1 and 7 against TK-2 could be accounted for by molecular modeling showing that two hydrogen bonds can be formed between the thiourea nitrogens of 7 and the oxygens of the gamma-phosphate of ATP. The importance of several active-site residues was assessed by site-directed mutagenesis experiments on TK-2 and the related HSV-1 TK. The low Ki/Km ratios for 1 and 7 (0.38 and 0.039 against dThd, and 0.75 and 0.12 against ATP, respectively) indicate that these compounds are amongst the most potent inhibitors of TK-2 described so far. In addition, a striking close correlation was found between the inhibitory activities of the test compounds against TK-2 and Mycobacterium tuberculosis thymidylate kinase that is strongly indicative of close structural and/or functional similarities between both enzymes in relation to their mode of interaction with these nucleoside analogue inhibitors. PMID: 19233899 [PubMed - as supplied by publisher] 16: J Clin Virol. 2009 Feb 20. [Epub ahead of print] Detection of herpes viruses in children with acute appendicitis. Katzoli P, Sakellaris G, Ergazaki M, Charissis G, Spandidos DA, Sourvinos G. Laboratory of Virology, Faculty of Medicine, University of Crete, Heraklion 71003, Crete, Greece. OBJECTIVE: This study aimed to investigate the incidence of herpes simplex virus (HSV) types-1 and -2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6) and human herpes virus 7 (HHV-7) in childhood acute appendicitis. STUDY DESIGN: Polymerase chain reaction (PCR) assays were applied to detect herpes virus DNA in 38 children [11 girls and 27 boys, mean age 9 years (STD+/-2.59), range 6-14 years], who underwent an appendectomy within a 2.5-year period. Appendix, omentum and peripheral blood mononuclear cells (PBMCs) were available from each case. Of the 38 children with acute appendicitis, 20 (52.6%) had advanced (phlegmonous) acute appendicitis and 18 (47.4%) had perforated appendicitis and local peritonitis. Forty-one blood specimens from age-matched healthy children (25 female and 16 male), with clinical manifestations unrelated to viral infections served as negative controls. RESULTS: CMV was the most frequently detected virus (8/38, 21%), followed by HHV-6 (3/38, 7.9%). EBV and HSV-1 were detected, though not in all three different types of tissue specimens tested. None of the samples examined were HSV-2-, VZV- or HHV-7-positive. Of all the specimens, the omentum was the most commonly infected tissue (63.0%) while the appendix and peripheral blood specimens were found to be positive for viral infection in 60.5% and 50% of cases, respectively. The CMV IgG+ antibodies were positive in 54% of the control cases while 86% of the same group presented HHV-6 IgG+ antibodies. CONCLUSION: To the best of our knowledge, this is the first study documenting the presence of herpes virus DNA in children with acute appendicitis, suggesting that possible viral infection or reactivation is associated with childhood appendicitis. PMID: 19233720 [PubMed - as supplied by publisher] 17: Pain. 2009 Feb 20. [Epub ahead of print] Controlled release oxycodone - An evidence-based treatment for pain in acute herpes zoster. Haanpaa M. Rehabilitation Centre ORTON, Tenholantie 10, FIN-00280 Helsinki, Finland; Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland. Publication Types: EDITORIAL PMID: 19233562 [PubMed - as supplied by publisher] 18: Eye. 2009 Feb 20. [Epub ahead of print] Herpes zoster ophthalmicus complicated by incomplete ophthalmoplegia and a neurotrophic ulcer. Chan EW, Sanjay S. [1] 1Department of Ophthalmology and Visual Sciences, Alexandra Hospital, Singapore, Singapore [2] 2Eye Clinic, Jurong Medical Centre, Singapore, Singapore. PMID: 19229277 [PubMed - as supplied by publisher] 19: Masui. 2009 Feb;58(2):153-9. [The effects of early nerve blocks for prevention of postherpetic neuralgia and analysis of prognostic factors] [Article in Japanese] Tajima K, Iseki M, Inada E, Miyazaki T. Department of Anesthesiology and Pain Medicine, Juntendo University of Medicine, Tokyo 113-0033. BACKGROUND: Herpes zoster causes acute pain and sometimes leads to postherpetic neuralgia (PHN). The previously reported risk factors of PHN such as old age, allodynia, paresthesia and so on are not based on evidence. Although nerve block is useful to relieve acute pain and recommended for prevention of PHN, evidence is scanty. METHODS: The patients with herpes zoster within 3 months after the onset were studied. The patient underwent nerve blocks and proper medical treatment, and were followed for up to one year. The risk factors of PHN were assessed. We evaluated whether nerve block prevented PHN. RESULTS: A total of 144 consecutive patients were studied. Twenty seven % of patients suffered PHN. Old age (> 65 y. o) and hypesthesia were confirmed to be the risk factors of PHN, whereas the intensity of acute pain was not. Patients who underwent nerve block within 1 month after the onset were less likely to suffer from PHN compared with patients of delayed nerve blocks. CONCLUSIONS: Old age, hypesthesia and delayed nerve blocks were the risk factors of PHN. Nerve blocks in the early phase of herpes zoster may be useful to prevent PHN, particularly in the younger patients. Publication Types: English Abstract PMID: 19227166 [PubMed - in process] 20: JAMA. 2009 Feb 18;301(7):774-5. Comment on: JAMA. 2009 Feb 18;301(7):737-44. Herpes zoster in the age of focused immunosuppressive therapy. Whitley RJ, Gnann JW Jr. Publication Types: Comment Editorial Research Support, N.I.H., Extramural PMID: 19224757 [PubMed - indexed for MEDLINE]