OBJECTIVETo investigate the clinical and laboratory features of patient with B cell lymphoma associated hemophagocytic syndrome(B-LAHS).

METHODSThe clinical data of 10 cases of B-LAHS were retrospectively analysed and the relevant literatures were reviewed.

RESULTSThe median age of 10 cases diagnosed as B-LAHS was 55.5 (31-88) years old, and median time from attack to diagnosis was 2 months (2 weeks-4 months). The diagnosis can be made histopathologically and immunohistochemically by bone marrow biopsy. Among them 7 cases were diagnosed as large B cell lymphoma, 2 cases as mantle cell lymphoma and 1 case as small B cell lymphoma. The prominent clinical symptoms and signs were persistent fever (100%) and splenomegaly(90%), and the involvements with respiratory and digestive system were common. Another 1 case had systemic muscle pain and lactic acidosis as the first onset. Laboratory studies showed hepatic dysfunction, significantly elevated ferritin and lactate dehydrogenase, abnormal lymphocytes in peripheral blood smear, and hemophagocytosis in bone marrow smear. The FSC/SSC abnormalities of cloned B lymphoma cells were detected through flow cytometry (FCM). The complete remission (CR) was maintained in 4 cases receiving immunochemotherapy based on rituximab.

CONCLUSIONB-LAHS possesses heterogeneous clinical manifestations and rapid deterioration. Bone marrow biopsy and immunohistochemical examination can confirm the diagnosis. FCM may improve the early diagnosis of B-LAHS.

OBJECTIVETo explore the lymphocytic clonal expansion in adult patients with Epstein-Barr virus-associated lymphoproliferative diseases (EBV+LPD), and to investigate the experimental methods for EBV+LPD cells so as to provide a more objective measure for the diagnosis, classification and prognosis in the early stage of this disease.

METHODSPeripheral blood samples from 5 patients with EBV+LPD, 4 patients with adult infectious mononucleosis(IM) as negative control and 3 patients with acute NK-cell leukemia(ANKL) as positive control were collected. Prior to immunochemotherapy, viral loads and clonality were analysed by flow cytometry (FCM), T cell receptor gene rearrangement (TCR) was detected by real-time polymerase chain reaction (RT-PCR), and diversity of EB virus terminal repeat (EBV-TR) was detected by Southern blot.

RESULTSFCM showed only 1 case with clonal TCRVβ in 5 patients with EBV+LPD, TCR clonal expansion could be detected both in patients with IM(4 of 4) and 4 patients with EBV+LPD(4 of 5), Out of patients with EBV+LPD, 1 patient displayed a monoclonal band and 2 patients showed oligoclonal bands when detecting EBV-TR by southen blot.

CONCLUSIONDetecting the diversity of EBV-TR by Southern blot may be the most objective way to reflex clonal transformation of EBV+LPD, which is of great benefit to the diagnosis, classification and prognosis in the early stage of this disease.

Objective: To investigate the clinicopathologic characteristics of intractable epilepsy. Methods: Based on the classification criteria proposed by the International League Against Epilepsy (ILAE), a retrospective analysis of the pathological characteristics was done in 822 patients who underwent epilepsy surgery in Sanbo Brain Hospital, Capital Medical University, from June 2008 to December 2012. Results: The mean age of epilepsy onset was 9.9 years, mean duration of epilepsy was 11.9 years. Complex partial seizures were the main presenting features. Histopathological study showed 33 cases (4.01%) with mild forms of cortical malformations, 690 cases (83.94%) with focal cortical dysplasia (FCD) and 99 cases with others (including 39 pure hippocampal sclerosis, 20 cystosclerosis, 19 Sturge-Weber syndrome, 8 tuberous sclerosis complex, 6 without significant pathological changes, 5 gyral malformations and 2 hamartoma). Among the 690 FCD cases, 106 were FCD typeⅠ, 91 were FCD typeⅡ and 493 were FCDⅢ(Ⅲa: 160, Ⅲb: 106, Ⅲc: 26 and Ⅲd: 201). Conclusions FCDⅢd is the most common histopathological subtype causing intractable epilepsy, mainly due to focal hypoxia/ischemia in the perinatal period, which results in scarring of local brain tissue; this is followed by other isolated forms of FCD (FCDⅠand FCDⅡ), and then FCD Ⅲa and FCD Ⅲb. The reason to distinguish isolated forms of FCD (types Ⅰ and Ⅱ) from FCD Ⅲ and to subclassify FCD Ⅲ is to allow better definition of cortical dyslamination. Therefore, the pathogenic factors of intractable epilepsy can be grouped in greater details, and facilitate the diagnosis and potential curative treatment of intractable epilepsy.

To explore the clinical characteristics, diagnosis, treatment outcome and prognosis of de novo CD5 positive diffuse large B cell lymphoma (CD5(+)DLBCL), clinical data of 10 patients with pathologically confirmed CD5(+)DLBCL were retrospectively analyzed. The results indicated that 9 out of 10 patients were older than 60 years. All cases were in III/IV stages according to Ann-Arbor Staging System. Bone marrow biopsy with immunohistochemistry showed lymphoma involvement in 5 cases. Nine patients received chemotherapy with anti-CD20 monoclonal antibody (Rituximab) except one. Five cases achieved CR, two cases achieved PR, two cases achieved SD, one case achieved PD. Eight cases died within 2 years because of relapse or disease progression, in which 3 cases developed central nervous system lymphoma. The median survival time was 16 (1-23) months, 2-year survival rate was 20.40%. It is concluded that de novo CD5(+) DLBCL is rare in clinic, but it is a kind of highly aggressive lymphoma with poor prognosis. So, new treatment strategy should be explored.
Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; CD5 Antigens ; metabolism ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Rituximab ; Survival Rate ; Treatment Outcome

The aim of this study was to analyze the clinical features and laboratory findings of adult Epstein-Barr virus associated T/NK cell lymphoproliferative disease (EBV+T/NK-LPD) and to investigate the early diagnosis and prognosis of EBV+T/NK-LPD. The clinical data of 19 adult patients with EBV+T/NK-LPD were retrospectively analyzed. The results indicated that there were 11 males and 8 females. The median age was 32 years (range: 20-70 years). The average duration from onset of symptoms to diagnosis was 3.5 months. The median survival time was 2.5 months. Unkown fever, hepatosplenomegaly, liver dysfunction and interstitial pneumonia were the main clinical features. High levels of β2-MG, LDH, TNF, IL-6 and significantly increased EBV-DNA level (median level > 10(6) copies/ml) were occurred in all the patients. Cytopenia was seen in 18 cases. Morphologically, atypical large granular lymphocytes and hemophagocytosis were common in bone marrow smears. Deletion of CD5 or CD7 were frequently observed in T/NK lymphocytes in bone marrow cells by flow cytometry. Bone marrow biopsy showed atypical lymphocyte interstitial infiltrated in 10 cases, while a few large cells infiltrated in 6 cases. Immunohistochemistry showed the expression of CD3(+)CD56(+) were seen in 2 cases, CD3(+)CD8(+) in 11 cases and CD3(+)CD4(+) in 3 cases. TIA-1 and EBER were positive in all biopsy specimens. Three cases underwent biopsy of lymph nodes showed reactive proliferations of lymphocytes. All the patients died of multiorgan failure. It is concluded that the fever, hepatosplenomegaly are the most common clinical features in adult EBV+T/NK-LPD, the bone marrow infiltration of EBV-infected T/NK lymphocytes and significantly increased EBV-DNA level can be observed in all cases, the clinical outcome of this disease is poor, these clinical and experimental features can be served as a reliable marker for the timely diagnosis of adult EBV+T/NK-LPD.
Adult ; Aged ; Epstein-Barr Virus Infections ; pathology ; Female ; Humans ; Immunophenotyping ; Killer Cells, Natural ; virology ; Lymphoproliferative Disorders ; pathology ; virology ; Male ; Middle Aged ; Retrospective Studies ; T-Lymphocytes ; virology ; Young Adult

Objective To study the pharmacokinetics of the quick-acting anti-motion capsules with a single dose in beagle dogs and its interaction,when combined with other drugs.Methods Six adult healthy Beagle dogs were randomly divided into 3 groups,each consisting of 2.The tri-preaparatum and tri-periodicity Latin square method was used in the experiment.During the first phase of the experiment,the animals of the 3groups were respectively administered the quick-acting anti-motion capsule and the control drugsdimenhydrinate and dextroamphetamine sulfate.During the second phase of the experiment,all the animals of the 3 groups were respectively given dimenhydrinate,dextroamphetamine sulfate and the quick-acting antimotion capsule.During the third phase of the experiment,the animals of the 3 groups were respectively given dextroamphetamine sulfate, the quick-acting anti-motion capsule and dimenhydrinate. Level of dextroamphetamine sulfate and dimenhydrimate in the serum were measured with LC/MS/MS.Through the access of pre-clinical pharmacokinetics studies,we estimated relative bioavailability and main the quick-acting anti-motion capsule pharmacokinetic parameters of,as characterized by dextroamphetamine sulfate and dimenhydrimate.Results No significant differences could be seen in the pharmacokinetic parameters including tmax 、lnCmax 、lnAUC0-24 following oral administration of a single dose of quick-acting anti-motion capsule and dextroamphetamine(P ＞ 0.05).Two one-sided t tests of the lnCmax and lnAUCo-24 indicated that the pharmacokinetic parameters of dextroamphetamine sulfate combined with dimenhydrimate and the ginger extract (quick-acting anti-motion capsule) do not change distinctly,when compared with those of dimenhydrimate (P ＞ 0.05 ).Conclusions No significant pharmacokinetic interaction could be noticed,when the components of the ginger extract (quick-acting anti-motion capsules ) were combined with dimenhydrimate and Dextroamphetamine sulfate.

Objective To study the pharmacokinetics of the quick-acting anti-motion capsules with a single dose in beagle dogs and its interaction,when combined with other drugs.Methods Six adult healthy Beagle dogs were randomly divided into 3 groups,each consisting of 2.The tri-preaparatum and tri-periodicity Latin square method was used in the experiment.During the first phase of the experiment,the animals of the 3groups were respectively administered the quick-acting anti-motion capsule and the control drugsdimenhydrinate and dextroamphetamine sulfate.During the second phase of the experiment,all the animals of the 3 groups were respectively given dimenhydrinate,dextroamphetamine sulfate and the quick-acting antimotion capsule.During the third phase of the experiment,the animals of the 3 groups were respectively given dextroamphetamine sulfate, the quick-acting anti-motion capsule and dimenhydrinate. Level of dextroamphetamine sulfate and dimenhydrimate in the serum were measured with LC/MS/MS.Through the access of pre-clinical pharmacokinetics studies,we estimated relative bioavailability and main the quick-acting anti-motion capsule pharmacokinetic parameters of,as characterized by dextroamphetamine sulfate and dimenhydrimate.Results No significant differences could be seen in the pharmacokinetic parameters including tmax 、lnCmax 、lnAUC0-24 following oral administration of a single dose of quick-acting anti-motion capsule and dextroamphetamine(P ＞ 0.05).Two one-sided t tests of the lnCmax and lnAUCo-24 indicated that the pharmacokinetic parameters of dextroamphetamine sulfate combined with dimenhydrimate and the ginger extract (quick-acting anti-motion capsule) do not change distinctly,when compared with those of dimenhydrimate (P ＞ 0.05 ).Conclusions No significant pharmacokinetic interaction could be noticed,when the components of the ginger extract (quick-acting anti-motion capsules ) were combined with dimenhydrimate and Dextroamphetamine sulfate.

BACKGROUNDPDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5. To elucidate the role of PDK1 in the heart, we investigated the cardiac phenotype of mice that lack PDK1 in the heart in different growth periods and the alteration of PDK1 signaling in human failing heart.

METHODSWe employed Cre/loxP system to generate PDK1(flox/flox): α-MHC-Cre mice, which specifically deleted PDK1 in cardiac muscle at birth, and tamoxifen-inducible heart-specific PDK1 knockout mice (PDK1(flox/flox):MerCreMer mice), in which PDK1 was deleted in myocardium in response to the treatment with tamoxifen. Transmural myocardial tissues from human failing hearts and normal hearts were sampled from the left ventricular apex to analyze the activity of PDK1/Akt signaling pathways by Western blotting.

RESULTSPDK1(flox/flox): α-MHC-Cre mice died of heart failure at 5 and 10 weeks old. PDK1(flox/flox) -MerCreMer mice died of heart failure from 5 to 21 weeks after the initiation of tamoxifen treatment at 8 weeks old. We found that expression levels of PDK1 in human failing heart tissues were significantly decreased compared with control hearts.

CONCLUSIONOur results suggest that PDK1 signaling network takes part in regulating cardiac viability and function in mice, and may be also involved in human heart failure disease.

3-Phosphoinositide-Dependent Protein Kinases ; Adult ; Animals ; Female ; Glycogen Synthase Kinase 3 ; physiology ; Heart ; physiology ; Heart Failure ; enzymology ; etiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Myosin Heavy Chains ; physiology ; Protein-Serine-Threonine Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; Tamoxifen ; pharmacology

OBJECTIVETo evaluate the practical method of vacuum sealing drainage (VSD) technique combined with sural neurovascular pedicle fasciocutaneous flap to repair deep wounds in the foot near the ankle joint with exposed bone and tendons.

METHODSFrom January 2006 to January 2009, 79 patients with deep wounds in the foot near the ankle joint with exposed bone and tendons were treated by VSD technique combined with sural neurovascular pedicle fasciocutaneous flap including 58 males and 21 females with an average age of 34 years old ranging from 7 to 59 years. There were 17 cases in low 1/3 part of leg and achilles tendon, 28 in lateral malleolus and lateral dorsum of foot, 21 in medial malleolus and medial dorsum of foot, 13 in heel and pelma. Firstly the wounds were debrided and cultivated by using VSD technique, then the soft tissue defections were repaired with sural neurovascular pedicle fasciocutaneous flap.

RESULTSThe area of flap was from 6 cm x 5 cm to 18 cm x 15 cm; All patients stayed in hospital for 14 to 30 days, 18 days in average. Living flaps of all patients were followed-up from 6 months to 3 years, the flaps of 2 patients were mostly necrotic, 3 were necrotic, 5 cases appeared obstacle of venous back streaming. The others survived with no infections.

CONCLUSIONThe wound would become fresh and clean as soon as possible with VSD. The sural neurovascular pedicle fasciocutaneous flap could provide a good covering for the exposed wound. Therefore the wound healed faster with friction resistance and fine appearance. The time of hospitalization were greatly shortened after combined application.

Adolescent ; Adult ; Ankle Joint ; surgery ; Child ; Drainage ; methods ; Female ; Foot Injuries ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Soft Tissue Injuries ; surgery ; Surgical Flaps ; Vacuum

OBJECTIVETo investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment.

METHODSMutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed.

RESULTSEGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation.

CONCLUSIONThe frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; pathology ; Codon ; Erlotinib Hydrochloride ; Exons ; Female ; Genes, erbB-1 ; Genes, ras ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking ; Young Adult ; ras Proteins ; genetics