1. Eur J Pediatr. 2010 Apr;169(4):421-5. Epub 2009 Aug 16.

Rapid diagnosis of herpetic encephalitis in children by PCR-microarray technology
for simultaneous detection of seven human herpes viruses.

Shi J, Wu Y, Cai M, Shang S.

Department of Laboratory, Children's Hospital, Zhejiang University School of
Medicine and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal
Diseases, Zhugan Xiang 57, 310003, Hangzhou, People's Republic of China.

The aim of the study was to evaluate retrospectively the usefulness of polymerase
chain reaction (PCR)-microarray technology, which can simultaneously detect seven
human herpes viruses for rapid and accurate diagnosis of herpetic encephalitis in
children. We simultaneously amplified herpes simplex virus type 1 and type 2
(HSV-1 and HSV-2); varicella-zoster virus; Epstein-Barr virus (EBV);
cytomegalovirus (CMV); and human herpes virus 6 (HHV-6A and HHV-6B) by multiplex 
PCR, and genotyped by DNA microarray technology. The multiplex primers and
oligonucleotide probes were designed and synthesized based on the highly
conserved regions of the DNA polymerase gene in human herpes viruses. Two hundred
ninety cerebrospinal fluid (CSF) specimens from children with clinical suspicion 
of viral encephalitis were screened by PCR-microarray technology. The results
were compared with those of TaqMan PCR kits of common herpes virus. The
PCR-microarray technology could detect as few as 10 copies of viral loads. There 
was no nonspecific hybridizing signal between probes and no cross-reaction to DNA
extracted from the pathogens we used. Of 290 cases, 11 were tested positive by
PCR-microarray technology. Among them, three were positive for HSV-1, two were
positive for HSV-2, one was positive for EBV, two were positive for CMV, two were
positive for HHV-6A, one was positive for HHV-6B, and one showed mixed infection 
of HSV-2 and CMV, and the positive rate was 3.8%. Compared with the results of
TaqMan PCR, the sensitivity of PCR-microarray technology was 91.7%, the
specificity was 100%, and the index of accurate diagnosis was 0.917. None of the 
30 control CSF specimens was tested positive in both methods. Our study suggests 
that the simultaneous detection of seven human herpes viruses by PCR-microarray
technology is the method of choice for rapid, accurate, and specific etiological 
diagnosis of herpetic encephalitis in children.

PMID: 19685343 [PubMed - in process]


2. Antimicrob Agents Chemother. 2010 Mar;54(3):1146-51. Epub 2009 Dec 28.

Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and
systemic circulation after administration of high-dose valacyclovir in subjects
with normal and impaired renal function.

Smith JP, Weller S, Johnson B, Nicotera J, Luther JM, Haas DW.

Division of Infectious Diseases, Vanderbilt University School of Medicine, 345
24th Avenue North, Suite 105, Nashville, TN 37203. david.w.haas@vanderbilt.edu.

Valacyclovir, the l-valyl ester prodrug of acyclovir (ACV), is widely prescribed 
to treat infections caused by varicella-zoster virus or herpes simplex virus.
Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By
mechanisms not fully understood, this occurs more frequently in the setting of
renal impairment. We characterized the steady-state pharmacokinetics of ACV and
its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir 
(8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We
administered multiple doses of high-dose valacyclovir to 6 subjects with normal
renal function and 3 subjects with chronic renal impairment (creatinine clearance
[CrCl], approximately 15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500
mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF 
sampling throughout the dosing interval. The average steady-state concentrations 
of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation
and the CSF among subjects with impaired renal function than among subjects with 
normal renal function. However, the CSF penetration of each analyte, reflected by
the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h
dosing interval (AUC(tau)) ratio, did not differ based on renal function. Renal
impairment does not alter the propensity for ACV or its metabolites to distribute
to the CSF, but the higher concentrations in the systemic circulation, as a
result of reduced elimination, are associated with proportionally higher
concentrations in CSF.

PMCID: PMC2825963 [Available on 2010/9/1]
PMID: 20038622 [PubMed - in process]


3. J Natl Cancer Inst. 2010 Feb 24. [Epub ahead of print]

Immune-Related and Inflammatory Conditions and Risk of Lymphoplasmacytic Lymphoma
or Waldenstrom Macroglobulinemia.

Kristinsson SY, Koshiol J, Bjorkholm M, Goldin LR, McMaster ML, Turesson I,
Landgren O.

Affiliations of authors: Department of Medicine, Division of Hematology,
Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden
(SYK, OL); Genetic Epidemiology Branch, Division of Cancer Epidemiology and
Genetics (JK, LRG, MLM, OL) and Center for Cancer Research (OL), National Cancer 
Institute, National Institutes of Health, Bethesda, MD; Department of Medicine,
Section of Hematology, Malmo University Hospital, Malmo, Sweden (IT).

Background Chronic immune stimulation appears to be associated with
lymphoplasmacytic lymphoma (LPL)-Waldenstrom macroglobulinemia (WM); however,
available information is sparse. We conducted, to our knowledge, the most
comprehensive study to date to evaluate associations between a personal or family
history of many immune-related and/or inflammatory disorders and the subsequent
risk of LPL-WM. Methods We used Swedish population-based registries to identify
2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 
first-degree relatives of either case patients or control subjects. We evaluated 
a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We
calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each
condition by use of logistic regression. Results An increased risk of LPL-WM was 
associated with a personal history of the following autoimmune diseases: systemic
sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjogren syndrome (OR = 12.1, 95% CI =
3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2),
polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis 
(OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with
a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95%
CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR 
= 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes
zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 
5.0). An increased risk of LPL-WM was associated with a family history of the
following autoimmune or infectious diseases: Sjogren syndrome (OR = 5.0, 95% CI =
2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2),
Guillain-Barre syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR =
2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3
to 2.7), and chronic prostatitis (OR = 4.3, 95% CI = 1.7 to 11.1). Conclusions
Personal history of certain immune-related and/or infectious conditions was
strongly associated with increased risk of LPL-WM. The association of both
personal and family history of Sjogren syndrome and autoimmune hemolytic anemia
with risk of LPL-WM indicates the potential for shared susceptibility for these
conditions.

PMID: 20181958 [PubMed - as supplied by publisher]


4. JAMA. 2010 Feb 24;303(8):733-4. Epub 2010 Jan 26.

Incomplete financial disclosures in an editorial, clinical crossroads, and reply 
letter related to herpes zoster.

Whitley RJ.

Comment on:
    JAMA. 2009 Jul 1;302(1):73-80.
    JAMA. 2009 Nov 4;302(17):1862; author reply 1862-3.
    JAMA. 2009 Feb 18;301(7):774-5.

PMID: 20103745 [PubMed - in process]


5. Clin Infect Dis. 2010 Feb 23. [Epub ahead of print]

Increasing Incidence of Herpes Zoster among Veterans.

Rimland D, Moanna A.

Atlanta Veterans Affairs Medical Center, Decatur, and 2Emory University School of
Medicine, Atlanta, Georgia.

Background. The incidence of herpes zoster in the United States has been
estimated to be 1 million cases annually, with a higher rate in adults older than
60 years. The morbidity of the disease, including postherpetic neuralgia, imposes
significant effects on quality of life. We analyzed reports of herpes zoster in
the Veterans Affairs (VA) population because these patients are older and could
provide a reflection of disease trends in the aging US population. These data
will provide a baseline for future analyses of the incidence of herpes zoster
after the introduction of the herpes zoster vaccine in late 2007. Methods. To
evaluate the trend in the annual incidence of herpes zoster for fiscal year 2000 
(beginning October 1999) through fiscal year 2007 (through September 2007), we
derived incidence rates using the Veterans Health Administration Decision Support
System reports of herpes zoster by International Classification of Diseases,
Ninth Revision codes from 2000 through 2007 and the corresponding denominator
data for all veterans in care. These rates were validated by review of medical
records of patients with diagnoses of herpes zoster at the Atlanta VA Medical
Center. Results. The annual incidence of herpes zoster increased from 3.10
episodes per 1000 veterans in 2000 to 5.22 in 2007 ([Formula: see text];
[Formula: see text]). This increasing rate was seen in both men and women but
only in groups older than 40 years. Conclusion. The increasing incidence of
herpes zoster in our veteran population and its effect on the quality of life of 
the veterans validate the need for improved rates of vaccination in this
population.

PMID: 20178416 [PubMed - as supplied by publisher]


6. J Clin Oncol. 2010 Feb 22. [Epub ahead of print]

Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in
Relapsed Patients With Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell
Lymphoma.

Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, 
Yamada Y, Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida
T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R.

Department of Hematology and Cell Therapy, Aichi Cancer Center; Department of
Clinical Pathophysiology and Department of Infectious Diseases, Nagoya University
Graduate School of Medicine; Department of Hematology and Oncology, Nagoya Daini 
Red Cross Hospital, Nagoya; Department of Clinical Pathology and Department of
Medical Oncology and Immunology, Nagoya City University Graduate School of
Medical Sciences, Nagaya; Department of Hematology, Imamura Bun-in Hospital;
Department of Internal Medicine, National Hospital Organization Kagoshima Medical
Center; Department of Hematology and Immunology, Kagoshima University Hospital,
Kagoshima; Hematology and Stem Cell Transplantation Division, National Cancer
Center Hospital; Department of Safety Research on Blood and Biologics, National
Institute of Infectious Diseases; Department of Molecular Preventive Medicine,
Graduate School of Medicine, The University of Tokyo; Kyowa Hakko Kirin Co Ltd,
Tokyo; Department of Hematology and Molecular Medicine Unit and Department of
Laboratory Medicine, Nagasaki University Graduate School of Biomedical Science,
Nagasaki; Department of Hematology, National Kyushu Cancer Center; The Department
of Medicine, Division of Medical Oncology, Infectious Disease, and Endocrinology,
School of Medicine, Fukuoka University, Fukuoka; and the Department of
Pathophysiology, Kurume University School of Medicine, Kurume, Japan.

PURPOSE: KW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4)
antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This
phase I study assessed the safety, pharmacokinetics, recommended phase II dose
and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell
leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL). PATIENTS AND
METHODS: Sixteen patients received KW-0761 once a week for 4 weeks by intravenous
infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg
by a 3 + 3 design. RESULTS: Fifteen patients completed the protocol treatment.
Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting
toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other
treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia 
(n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion
reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of
toxicities increased with dose escalation. The maximum tolerated dose was not
reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg.
No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum
and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to
increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) 
achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial
(0.01; 2 at 1.0 mg/kg) responses. CONCLUSION: KW-0761 was tolerated at all the
dose levels tested, demonstrating potential efficacy against relapsed
CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are 
thus warranted.

PMID: 20177026 [PubMed - as supplied by publisher]


7. J Clin Virol. 2010 Feb 22. [Epub ahead of print]

Disease burden of herpes zoster in Korea.

Choi WS, Noh JY, Huh JY, Jo YM, Lee J, Song JY, Kim WJ, Cheong HJ.

Division of Infectious Disease, Department of Internal Medicine, Korea University
College of Medicine, Seoul, Republic of Korea.

BACKGROUND: The occurrence of herpes zoster can deteriorate the quality of life
considerably, resulting in high disease burden. While Korea is assumed to have
high disease burden of herpes zoster, there has been no researches analyzing
this. OBJECTIVES: We performed this study to investigate the disease burden of
herpes zoster in the Korean population as a whole. STUDY DESIGN: We used the
database of the Health Insurance Review & Assessment Service of Korea and
analyzed the data of patients who had herpes zoster as a principal diagnosis
during the period from 2003 to 2007. We investigated the annual prevalence, rate 
of clinical visits, rate of hospitalization, and the pattern of medical services 
use. The socioeconomic burden of herpes zoster was calculated by a conversion
into cost. RESULTS: Rates of clinic visits and hospitalizations due to herpes
zoster during the 5-year period from 2003 to 2007 were 7.93-12.54 per 1000
population and 0.22-0.32 per 1000 population, respectively. Prevalence rates
according to age increased sharply after 50 years and reached a peak at 70 years.
The total socioeconomic cost of herpes zoster was $75.9-143.8 million per year,
increasing every year by 14-20%. CONCLUSIONS: There is a heavy socioeconomic
burden due to herpes zoster in Korea and indicate that appropriate policies need 
to be established to reduce this burden. Additional researches are also necessary
to assess the safety, efficacy and cost-effectiveness of a herpes zoster vaccine 
in the Korean population. Copyright © 2010 Elsevier B.V. All rights reserved.

PMID: 20181512 [PubMed - as supplied by publisher]


8. J Pharmacol Sci. 2010 Feb 20. [Epub ahead of print]

Blockade of Glycine Transporter (GlyT) 2, but Not GlyT1, Ameliorates Dynamic and 
Static Mechanical Allodynia in Mice With Herpetic or Postherpetic Pain.

Nishikawa Y, Sasaki A, Kuraishi Y.

Department of Applied Pharmacology, Graduate School of Medicine and
Pharmaceutical Sciences, University of Toyama, Japan.

Glycine is an inhibitory neurotransmitter in the spinal dorsal horn and its
extracellular concentration is regulated by glial glycine transporter (GlyT) 1
and neuronal GlyT2. This study was conducted to elucidate the effects of
intrathecal injections of GlyT1 and GlyT2 inhibitors on two distinct types of
mechanical allodynia, dynamic and static allodynia, in mice with herpetic or
postherpetic pain. The GlyT2 inhibitor ALX1393, but not the GlyT1 inhibitor
sarcosine, suppressed dynamic and static allodynia at the herpetic and
postherpetic stages. Intrathecal ALX1393 suppressed dynamic allodynia induced by 
intrathecal strychnine and N-methyl-D-aspartate (NMDA). Intrathecal sarcosine
suppressed dynamic allodynia induced by intrathecal strychnine, but not NMDA.
Expression level of GlyT1, but not GlyT2, mRNA in the lumbar dorsal horn was
decreased at the herpetic and postherpetic stages. Glycine receptor
alpha1-subunit mRNA was decreased in the lumbar dorsal horn at the herpetic, but 
not postherpetic stage, without alteration in alpha3-subunit mRNA. The results
suggest that GlyT2 is a potential target for treatment of dynamic and static
allodynia in patients with herpes zoster and postherpetic neuralgia. The lack of 
efficacy of GlyT1 inhibitor may be explained by activation of NMDA receptors and 
the down-regulation of GlyT1 in the lumbar dorsal horn.

PMID: 20173309 [PubMed - as supplied by publisher]


9. Hautarzt. 2010 Feb 19. [Epub ahead of print]

[Skin infections after transplantation.]

[Article in German]

Wolf IH.

Universitatsklinik fur Dermatologie und Venerologie, Abteilung fur Allgemeine
Dermatologie, Medizinische Universitat Graz, Auenbruggerplatz 8, 8036, Graz,
Osterreich, ingrid.wolf@medunigraz.at.

Skin infections after transplantation are frequent and of special importance
because they may be quite severe. The spectrum of dermatologic infections in
transplant recipients includes bacterial, mycotic and viral diseases. Pyoderma,
herpes virus 6/7, herpes simplex virus, varicella-zoster virus, cytomegalovirus
and candida infections predominate. Rare pathogens must be also considered.
Cutaneous infections can be divided into three phases following transplantation. 
Diagnosis and adequate early therapy together with specific prophylaxis and
follow-up of transplant patients should be strived for to avoid life-threatening 
complications.

PMID: 20165826 [PubMed - as supplied by publisher]


10. Aliment Pharmacol Ther. 2010 Feb 18. [Epub ahead of print]

Infliximab as rescue medication for patients with severe ulcerative/indeterminate
colitis refractory to tacrolimus.

Herrlinger KR, Barthel DN, Schmidt KJ, Buning J, Barthel CS, Wehkamp J, Stange
EF, Fellermann K.

Department of Gastroenterology, Hepatology and Endocrinology,
Robert-Bosch-Hospital, Stuttgart, Germany.

SUMMARY Background: The calcineurin inhibitor tacrolimus and the
anti-TNF-antibody infliximab are established options in steroid refractory
ulcerative colitis (UC). The aim of this study was to determine the efficacy of
infliximab as rescue medication in patients failing to respond to tacrolimus.
Aim: To evaluate the efficacy of infliximab-salvage therapy in patients with
refractory ulcerative colitis failing to respond to tacrolimus Methods:
Twenty-four patients were enrolled in this evaluation. Reasons for tacrolimus
therapy were steroid-refractory disease in 19 patients and steroid dependency in 
5 patients. All patients receiving infliximab had tacrolimus refractory active
disease (Lichtiger score >10) and were treated with 5mg/kg at weeks 0, 2 and 6
and every 8 weeks thereafter if tolerated. Results: Six of 24 patients (25%)
achieved remission following infliximab infusion and 4/24 (17%) had an initial
response only but underwent proctocolectomy later due to loss of response (3) or 
development of a delayed hypersensitivity reaction (1). Fourteen patients (58%)
completely failed to respond with 10 undergoing colectomy. Eight patients
experienced side effects under infliximab including two infectious complications 
(herpes zoster and herpes pneumonia). Conclusions: Infliximab offers a
therapeutic option as rescue therapy in about a quarter of patients with active
UC after failing to respond to tacrolimus. This benefit has to be weighed against
the risks of infectious complications.

PMID: 20175769 [PubMed - as supplied by publisher]


11. J Virol Methods. 2010 Feb 17. [Epub ahead of print]

The glycoproteins C and G are equivalent target antigens for the determination of
herpes simplex virus type 1-specific antibodies.

Scheper T, Saschenbrecker S, Steinhagen K, Sauerbrei A, Suer W, Meyer W,
Schlumberger W, Wandinger KP.

Institute of Experimental Immunology, affiliated to EUROIMMUN AG, Seekamp 31,
D-23560 Luebeck, Germany; These authors contributed equally to this work.

Seroreactivity to the glycoproteins C and G of herpes simplex virus type 1
(HSV-1) was compared in 310 serum samples using a Western blot assay containing a
whole antigen extract of HSV-1 and an ELISA employing gC1 isolated from HSV-1.
The prevalence of reactivity to gC1 was 75.8% by Western blot and 73.9% by ELISA,
while antibody responses to gG1 were detected in 72.9% of sera by Western blot.
An absolute correlation of 96.1% between the reactivity to gC1 and gG1 was
demonstrated using the Western blot. The gC1-based ELISA correlated with Western 
blot detection of anti-gC1 and anti-gG1 antibodies in 95.2% and 97.7% of samples,
respectively. 3.2% of all sera were reactive with gC1 in Western blot and/or
ELISA, but were negative for anti-gG1. For analysis of cross-reactivity,
antibodies against HSV-2, Epstein-Barr virus, varicella-zoster virus and
cytomegalovirus were determined. The prevalence of antibodies against each
individual virus was identical in the groups of sera reactive with gC1 or gG1.
These findings indicate that gC1 and gG1 are equivalent antigenic targets for the
type-specific serodiagnosis of HSV-1 infections. Copyright © 2010. Published by
Elsevier B.V.

PMID: 20171247 [PubMed - as supplied by publisher]


12. J Neurol. 2010 Feb 13. [Epub ahead of print]

Trigeminal herpes zoster and Ramsay Hunt Syndrome with a lesion in the spinal
trigeminal nucleus and tract.

Hung CW, Wang SJ, Chen SP, Lirng JF, Fuh JL.

Department of Neurology, Yangming Branch, Taipei City Hospital, Taipei, Taiwan,
ROC.

We report the case of a 77-year-old immuno-competent man who developed herpes
zoster in the maxillary and mandibular branches of the trigeminal nerve. Within 3
weeks, he developed ipsilateral peripheral facial palsy, hearing loss, vesicles
over the external auditory canal, and pain in the face and ear. A T(2)-weighted
MRI of the brain revealed a hyper-intense lesion at the right medulla
corresponding to the spinal trigeminal nucleus and tract. Gadolinium enhancement 
was seen over the right facial nerve. These lesions suggest a possibility of
transaxonal spread of the varicella zoster virus between the trigeminal nerve,
the facial nerve, and the spinal trigeminal nucleus and tract.

PMID: 20155276 [PubMed - as supplied by publisher]


13. Nat Rev Rheumatol. 2010 Feb 9. [Epub ahead of print]

Tumor necrosis factor blockade and the risk of viral infection.

Kim SY, Solomon DH.

Division of Rheumatology, Immunology, and Allergy, and Division of
Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 75
Francis Street, Boston, MA 02115, USA.

Tumor necrosis factor (TNF) blockers are widely used to treat rheumatoid
arthritis and other chronic inflammatory diseases. Many studies have demonstrated
an increased risk of opportunistic infections such as tuberculosis and fungal
infection in patients treated with TNF blockers, which is thought to be related
to the primary role of TNF both in host defense and in the immune response.
Little is known, however, about the association between TNF blockade and the
development of viral infection. Owing to the critical role of TNF in the control 
of viral infection, depletion of this cytokine with TNF blockers could facilitate
the development or reactivation of viral infection. A number of large
observational studies have found an increased risk of herpes zoster in patients
receiving TNF blockers for the treatment of rheumatoid arthritis. This Review
draws attention to the risk of several viral infections, including HIV, varicella
zoster virus, Epstein-Barr virus, cytomegalovirus, and human papillomavirus, in
patients receiving TNF-blocking therapy for chronic inflammatory conditions. In
addition, implications for clinical practice and possible preventative approaches
are discussed.

PMID: 20142812 [PubMed - as supplied by publisher]


14. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2461-6. Epub 2010 Jan 21.

Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1
DNA replication components.

Peng H, Nogueira ML, Vogel JL, Kristie TM.

Laboratory of Viral Diseases, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bld 4-131, 4 Center Drive, Bethesda, MD 
20892, USA.

The cellular transcriptional coactivator HCF-1 interacts with numerous
transcription factors as well as other coactivators and is a component of
multiple chromatin modulation complexes. The protein is essential for the
expression of the immediate early genes of both herpes simplex virus (HSV) and
varicella zoster virus and functions, in part, by coupling chromatin modification
components including the Set1 or MLL1 histone methyltransferases and the histone 
demethylase LSD1 to promote the installation of positive chromatin marks and the 
activation of viral immediately early gene transcription. Although studies have
investigated the role of HCF-1 in both cellular and viral transcription, little
is known about other processes that the protein may be involved in. Here we
demonstrate that HCF-1 localizes to sites of HSV replication late in infection.
HCF-1 interacts directly and simultaneously with both HSV DNA replication
proteins and the cellular histone chaperone Asf1b, a protein that regulates the
progression of cellular DNA replication forks via chromatin reorganization. Asf1b
localizes with HCF-1 in viral replication foci and depletion of Asf1b results in 
significantly reduced viral DNA accumulation. The results support a model in
which the transcriptional coactivator HCF-1 is a component of the HSV DNA
replication assembly and promotes viral DNA replication by coupling Asf1b to DNA 
replication components. This coupling provides a novel function for HCF-1 and
insights into the mechanisms of modulating chromatin during DNA replication.

PMID: 20133788 [PubMed - in process]


15. N Engl J Med. 2010 Feb 4;362(5):416-26. Epub 2010 Jan 20.

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis.

Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sorensen P,
Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ; CLARITY Study Group.

Collaborators: Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg
Sorensen P, Vermersch P, Sandberg-Wollheim M, Cuzick J, Juliusson G, Reingold S, 
King J, Pollard J, Sedal L, Aichner F, Eggers C, Dive D, Medaer R, Ferreira M,
Manchev I, Milanov I, Haralanov L, Deleva N, Petrova N, Bozhinov P, Zahariev Z,
Stamenov B, Shotekov P, Petrov I, Moskov R, Emond F, Freedman M, Grand'Maison F, 
Jacques F, Vorobeychik G, Demarin V, Kovacicek M, Lusic I, Perhat-Bucevic T,
Havrdova E, Talab R, Kanovsky P, Soelberg Sorensen P, Petersen T, Gross-Paju K,
Kalbe I, Toomsoo T, Elovaara I, Eralinna JP, Reunanen M, Clavelou P, Damier P,
Debouverie M, Edan G, Gout O, Labauge P, Laplaud D, Wiertlewski S, Vermersch P,
Heidenreich F, Maurer M, Kieseier B, Limmroth V, Oschmann P, Schimrigk S,
Steinbrecher A, Zettl U, Ziemann U, Karageorgiou K, Kyritsis A, Papadimitriou A, 
Amato MP, Bernardi G, Morra VB, Comi G, Galgani S, Gallo P, Patti F, Marrosu M,
Pozzilli C, Trojano M, Mancardi GL, Gebeily S, Koussa S, Wehbe M, Yamout B,
Vaitkus A, Metra M, Messouak O, Mossaddaq R, Slassi I, Yahyaoui M, Hupperts RM,
Czlonkowska A, Kozubski W, Nyka W, Selmaj K, Szczudlik A, Figueiredo J, Pedrosa
R, Alifirova V, Balyazin V, Barbarash O, Belova A, Boyko A, Gusev E, Elchaninov
A, Jacoupov E, Julev N, Kotov S, Kudryavtsev A, Laskov V, Lesnyak O, Odinak M,
Pasechnik E, Poverennonva I, Skoromets A, Spirin N, Stolyarov I, Vorobieva O,
Voskresenskaya O, Zaslavskiy L, Zonova E, Bohlega S, El-Jumah M, Drulovic J, Nadj
C, Goebels N, Schluep M, Ayed-Frih M, Hentati F, Mhiri C, Mrabet A, Mrissa R,
Idiman E, Karabudak R, Turan OF, Ahmed F, Constantinescu C, Giovannoni G, Hawkins
C, Palace J, Sharrack B, Loganovsky K, Moskovko S, Nehrych T, Voloshyna NP,
Carlini W, Cook S, English J, Garmany G, Glyman S, Huddlestone J, Hurwitz B,
Kresa-Reahl K, Mikol D, Pardo G, Rammohan K, Rao H, Reif M, Thrower B, Royal W,
Webb R, Wynn D, Naga C, Allen N, Lin K, Stefoski D, Balabanov R.

Queen Mary University London, the Blizard Institute of Cell and Molecular
Science, Barts and the London School of Medicine and Dentistry, London, United
Kingdom. g.giovannoni@qmul.ac.uk

Comment in:
    N Engl J Med. 2010 Feb 4;362(5):456-8.

BACKGROUND: Cladribine provides immunomodulation through selective targeting of
lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a
short-course oral tablet therapy in patients with relapsing-remitting multiple
sclerosis. METHODS: We randomly assigned 1326 patients in an approximate 1:1:1
ratio to receive one of two cumulative doses of cladribine tablets (either 3.5 mg
or 5.25 mg per kilogram of body weight) or matching placebo, given in two or four
short courses for the first 48 weeks, then in two short courses starting at week 
48 and week 52 (for a total of 8 to 20 days per year). The primary end point was 
the rate of relapse at 96 weeks. RESULTS: Among patients who received cladribine 
tablets (either 3.5 mg or 5.25 mg per kilogram), there was a significantly lower 
annualized rate of relapse than in the placebo group (0.14 and 0.15,
respectively, vs. 0.33; P<0.001 for both comparisons), a higher relapse-free rate
(79.7% and 78.9%, respectively, vs. 60.9%; P<0.001 for both comparisons), a lower
risk of 3-month sustained progression of disability (hazard ratio for the 3.5-mg 
group, 0.67; 95% confidence interval [CI], 0.48 to 0.93; P=0.02; and hazard ratio
for the 5.25-mg group, 0.69; 95% CI, 0.49 to 0.96; P=0.03), and significant
reductions in the brain lesion count on magnetic resonance imaging (MRI) (P<0.001
for all comparisons). Adverse events that were more frequent in the cladribine
groups included lymphocytopenia (21.6% in the 3.5-mg group and 31.5% in the
5.25-mg group, vs. 1.8%) and herpes zoster (8 patients and 12 patients,
respectively, vs. no patients). CONCLUSIONS: Treatment with cladribine tablets
significantly reduced relapse rates, the risk of disability progression, and MRI 
measures of disease activity at 96 weeks. The benefits need to be weighed against
the risks. (ClinicalTrials.gov number, NCT00213135.) 2010 Massachusetts Medical
Society

PMID: 20089960 [PubMed - indexed for MEDLINE]


16. N Engl J Med. 2010 Feb 4;362(5):402-15. Epub 2010 Jan 20.

Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.

Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J,
Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S,
Aradhye S, Kappos L; TRANSFORMS Study Group.

Collaborators: Cohen J, Barkhof F, Comi G, Hartung HP, Kappos L, Khatri B,
Montalban X, Pelletier J, Easton JD, Calandra T, DiMarco J, Hudson L, Kesselring 
J, Laupacis A, Temkin N, Weinshenker B, Zarbin M, Barkhof F, Poppe P, Luetic G,
Cristiano E, Caceres F, Garcea O, Correale J, Ballario C, Piedrabuena R, Pollard 
J, Beran R, Hodgkinson S, Schwartz R, Heard R, King J, Butzkueven H, Maida EM,
Vass K, Franta-Elmer C, Berger T, Aichner F, Ladurner G, Bissay V, Sindic C,
D'Hooghe M, Mulleners E, Damasceno B, Barreira A, Naylor R, Alvarenga R, Bacellar
A, Haussen S, Duquette P, Antel J, Lamontagne A, Grand'maison F, Freedman M,
Christie S, O'Connor P, Vorobeychik G, Devonshire V, Ramadan M, Hamdy S, Reda E, 
Hashem S, Fouad M, Lebrun-Frenay C, Pelletier J, Clanet M, Brochet B, Debouverie 
M, Heinzlef O, Ziemssen T, Koehler W, Tiel-Wilck K, Bachus R, Altmann N, Faiss J,
Baum K, Dressel A, Luckner K, Ebke M, Stangel M, Hartung HP, Diener HC, Bethke F,
Limmroth V, Maschke M, Thoemke F, Reifschneider G, Diehm R, Wildemann B, Melms A,
Rauer S, Karlbauer G, Berthele A, Lang M, Tumani H, Krauseneck P, Klein M,
Papadimitriou A, Karageorgiou K, Liakopoulos D, Tascos N, Plaitakis A,
Papathanasopoulos P, Panczel G, Jakab G, Csiba L, Komoly S, Csanyi A, Bartos L,
Centonze D, Pozzilli C, Marrosu MG, Bertolotto A, Mancardi G, Scarpini E, Comi G,
Protti A, Ghezzi A, Capra R, Bergamaschi R, Gallo P, Stecchi S, Montanari E, Tola
MR, Amato MP, Silvestrini M, Lugaresi A, Trojano M, Brescia Morra V, Ruggieri S, 
Patti F, Kim SM, Lee KH, Kim HJ, Park SP, Ginestal R, Salgado AV, Fontoura P,
Cunha L, Sousa L, Sa MJ, Pedrosa R, Montalban X, Arbizu T, Arroyo R, Garcia
Merino JA, Fernandez O, Izquierdo G, Casanova B, Antiguedad A, Goebels N, Kappos 
L, Young C, Lee M, Chaudhuri A, Nicholas R, Chinea Martinez A, Preiningerova J,
Greco D, Gross J, Newman S, Mitchell G, Pawar G, Freedman SM, Kaufman M, Absher
J, Kantor D, Ayala R, Honeycutt W, Shafer S, Steingo B, Delgado S, Cascione M,
Brock C, Keegan A, LaGanke C, Hunter S, Wilson E, Cohen J, Mazhari A, Bauer W,
Khatri B, Singer B, Lynch S, Rowe V, Hutton G, Gazda S, Dihenia B, Campagnolo D, 
Chippendale T, Ash P, Jung L, Olek M.

Mellen Center, Cleveland Clinic, Cleveland, OH 44195, USA. cohenj@ccf.org

Comment in:
    N Engl J Med. 2010 Feb 4;362(5):456-8.

BACKGROUND: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator
that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and
improvement on imaging in a phase 2 study involving patients with multiple
sclerosis. METHODS: In this 12-month, double-blind, double-dummy study, we
randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who
had a recent history of at least one relapse to receive either oral fingolimod at
a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a (an
established therapy for multiple sclerosis) at a weekly dose of 30 microg. The
primary end point was the annualized relapse rate. Key secondary end points were 
the number of new or enlarged lesions on T(2)-weighted magnetic resonance imaging
(MRI) scans at 12 months and progression of disability that was sustained for at 
least 3 months. RESULTS: A total of 1153 patients (89%) completed the study. The 
annualized relapse rate was significantly lower in both groups receiving
fingolimod--0.20 (95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg
group and 0.16 (95% CI, 0.12 to 0.21) in the 0.5-mg group--than in the interferon
group (0.33; 95% CI, 0.26 to 0.42; P<0.001 for both comparisons). MRI findings
supported the primary results. No significant differences were seen among the
study groups with respect to progression of disability. Two fatal infections
occurred in the group that received the 1.25-mg dose of fingolimod: disseminated 
primary varicella zoster and herpes simplex encephalitis. Other adverse events
among patients receiving fingolimod were nonfatal herpesvirus infections,
bradycardia and atrioventricular block, hypertension, macular edema, skin cancer,
and elevated liver-enzyme levels. CONCLUSIONS: This trial showed the superior
efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in
patients with multiple sclerosis, as compared with intramuscular interferon
beta-1a. Longer studies are needed to assess the safety and efficacy of treatment
beyond 1 year. (ClinicalTrials.gov number, NCT00340834.) 2010 Massachusetts
Medical Society

PMID: 20089954 [PubMed - indexed for MEDLINE]


17. J Neurol. 2010 Feb 3. [Epub ahead of print]

The clinical course of idiopathic acute transverse myelitis in patients from Rio 
de Janeiro.

Alvarenga MP, Thuler LC, Neto SP, Vasconcelos CC, Camargo SG, Alvarenga MP,
Papais-Alvarenga RM.

Departamento de Neurologia, Universidade Federal do Estado do Rio de Janeiro, Rua
Mariz e Barros 775, Tijuca, Rio de Janeiro, 20270-004, Brazil,
alvarenga_marina@hotmail.com.

The aim of this study was to describe the demographic, clinical and laboratory
features of idiopathic acute transverse myelitis (IATM). Patients with
non-compressive ATM receiving care at Hospital da Lagoa, Rio de Janeiro (Brazil) 
between 2000 and 2008 were selected. Of the 70 cases of acute myelopathies, the
idiopathic form was identified in 41 following exclusion of the cases associated 
with systemic lupus erythematosus (n = 1), Sjogren's syndrome (n = 1), herpes
zoster (n = 1), cytomegalovirus in an HIV-positive patient (n = 1), Schistosoma
mansoni (n = 1), actinic myelitis (n = 1), infectious myelitis of unknown
etiology (n = 2) and those that, following the first attack of myelitis,
converted to NMO (n = 19) or to clinically defined MS (n = 2). Of the 41 cases of
IATM, the majority of patients were female (68.3%) and white (65.9%). Median age 
at first myelitis was 37.0 +/- 11.8 years. Over a median observation time of 36
months, 39.0% of patients remained monophasic, while recurrences occurred in
61.0% of cases. The number of ATM/patient ranged from one to seven. Among the
recurrent cases the median time between the first and the second ATM was 12
months (range 1-150 months).The first myelitis was characterized mainly by
partial myelitis with motor and sensorial dysfunction (63.4%). Complete and
severe myelitis occurred more frequently among monophasic patients and partial
myelitis with moderate dysfunction at onset in recurrent cases; however, over the
long-term, dysfunction and disability were mild in both groups. Serial spine MRI 
confirmed spinal cord inflammation in 92.0% of cases and extensive spinal cord
lesion was identified in 61.0%. Brain MRI was normal or not suggestive of MS in
94.4% of cases. CSF showed pleocytosis in 41.2%, increased IgG index in 24.0% and
oligoclonal bands in 38.0% of 34 patients tested. Abnormal visual evoked
potentials occurred in 11.5% of 26 patients. Positivity for anti-AQP4 was found
in 23.5% of the 17 cases tested, suggesting limited forms of NMO. This study
suggests some new aspects of the clinical course of IATM such as the high
conversion rate to NMO, the predominance of women and a higher frequency of
recurrent forms.

PMID: 20127351 [PubMed - as supplied by publisher]


18. J Virol. 2010 Feb 3. [Epub ahead of print]

Impact of varicella zoster virus on dendritic cell subsets in human skin during
natural infection.

Huch JH, Cunningham AL, Arvin AM, Nasr N, Santegoets SJ, Slobedman E, Slobedman
B, Abendroth A.

Department of Infectious Diseases and Immunology, University of Sydney, New South
Wales 2006, Australia; Centre For Virus Research, Westmead Millennium Institute
and University of Sydney, Westmead, New South Wales 2145, Australia; Departments 
of Pediatrics and Microbiology and Immunology, Stanford University School of
Medicine, Stanford, CA 94305, USA; Department of Pathology, VU University Medical
Center, De Boelelaan 1117, Amsterdam 1081HV, The Netherlands; Laverty Pathology, 
North Ryde, New South Wales, 2113, Australia.

Varicella zoster virus (VZV) causes varicella and herpes zoster, diseases
characterized by distinct cutaneous rashes. DC are essential for inducing
anti-viral immune responses, however the contribution of DC subsets to the immune
control during natural cutaneous VZV infection has not been investigated.
Immunostaining showed that compared to normal skin, the proportion of cells
expressing DC-SIGN (dermal DC marker) or DC-LAMP and CD83 (mature DC markers)
were not significantly altered in infected skin. In contrast, the frequency of
Langerhans cells was significantly decreased in VZV infected skin, whereas there 
was an influx of plasmacytoid DC, a potent secretor of type I IFN. Langerhans
cells and plasmacytoid DC in infected skin were closely associated with VZV
antigen positive cells, and some Langerhans cells and plasmacytoid DC were VZV
antigen positive. To extend these in vivo observations, both plasmacytoid DC
(PDC) isolated from human blood and Langerhans cells derived from MUTZ-3 cells
were shown to be permissive to VZV infection. In VZV infected PDC cultures
significant induction of IFN-alpha did not occur, indicating the VZV inhibits the
capacity of PDC to induce expression of this host defense cytokine. This study
defines changes in the response of DC which occur during cutaneous VZV infection,
and implicates infection of DC subtypes in VZV pathogenesis.

PMID: 20130046 [PubMed - as supplied by publisher]


19. Vaccine. 2010 Feb 3;28(5):1217-20. Epub 2009 Nov 26.

Disease burden and epidemiology of herpes zoster in pre-vaccine Taiwan.

Lin YH, Huang LM, Chang IS, Tsai FY, Lu CY, Shao PL, Chang LY; Varicella-Zoster
Working Group; Advisory Committee on Immunization Practices, Taiwan.

Department of Pediatrics, Cardinal Tien Hospital, Yong Ho Branch, Taiwan.

Herpes zoster, a common disease, has an important impact on the health of adults,
particularly the elderly, and the health system. This study evaluated the disease
burden and epidemiological characteristics of herpes zoster in Taiwan. Using
herpes zoster-related ICD-9-CM codes used on Taiwan's National Health Insurance
claims, we analyzed overall and age group differences in incidence,
complications, utilization of healthcare facilities, lengths of stay, and cost of
their medical care in Taiwan's population from 2000 to 2005. The overall annual
incidence of zoster was 4.97 cases per 1000 people, with women having a
significantly higher incidence than men (5.20 per 1000 vs. 4.72 per 1000,
p<0.001). The incidence increased stepwise with age, with 5.18 cases per 1000 in 
people 40-50 years old, 8.36 in those 50-60, 11.09 in those 60-70, and 11.77 in
those above 70 years old. The estimated lifetime risk of developing herpes zoster
was 32.2%. Zoster-related hospitalizations and medical cost per patient increased
with age. In conclusion, about two-thirds of Taiwan's zoster cases occur in
adults older than 40 years old and about one-third of the population would
develop zoster within their lifetime. (c) 2009 Elsevier Ltd. All rights reserved.

PMID: 19944790 [PubMed - indexed for MEDLINE]


20. Am J Ophthalmol. 2010 Feb;149(2):214-220.e3. Epub 2009 Nov 11.

Late varicella-zoster virus dendriform keratitis in patients with histories of
herpes zoster ophthalmicus.

Hu AY, Strauss EC, Holland GN, Chan MF, Yu F, Margolis TP.

Ocular Inflammatory Disease Center, Jules Stein Eye Institute and the Department 
of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles,
California, USA.

PURPOSE: To describe the characteristics and course of late varicella-zoster
virus (VZV) dendriform keratitis in patients with histories of herpes zoster
ophthalmicus (HZO); to describe responses of corneal lesions to antiviral
treatment; and to investigate risk factors for recurrence. DESIGN: Retrospective 
case series. METHODS: Included were patients known to have 1 or more episodes of 
dendriform lesions beginning at least 2 weeks after HZO in 2 academic practices. 
Epithelial lesions were evaluated for the presence of VZV DNA by a polymerase
chain reaction assay. Demographic, medical, and ophthalmic data were collected
for each episode. Responses to treatment with antiviral medications were
evaluated. Cumulative risk of recurrence was determined using Kaplan-Meier
analysis; potential risk factors for recurrence (age, systemic disease, lesion
characteristics, corticosteroids) were evaluated using univariate Cox
proportional hazard models. RESULTS: We identified 20 patients (14 women; median 
age, 65 years) who met inclusion criteria. Dendriform lesions were pleomorphic
with thickened, opaque epithelium. Seven patients had systemic diseases
characterized by altered immune function. VZV DNA was identified in 15 of 16
cases tested, and all lesions responded to antiviral therapy. The 1-year
incidence of first recurrence was 95.8 lesions per 100 person-years of follow-up.
Patients had multiple recurrences, but risk of recurrence appeared to decrease
over time. No statistically significant risk factors for recurrence were
identified. CONCLUSIONS: Late dendriform lesions associated with HZO are foci of 
productive VZV infection. Lesions can be treated effectively with topical or
systemic antiviral agents. Patients can have multiple recurrences of dendriform
lesions despite treatment. Copyright (c) 2010 Elsevier Inc. All rights reserved.

PMID: 19909942 [PubMed - indexed for MEDLINE]