Chemoradiation combined with regional hyperthermia for advanced oesophageal cancer: a systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Hyperthermia is an effective treatment modality that augments the anticancer effects of radiotherapy and chemotherapy. Hyperthermia-chemo-radiotherapy (HCRT) is a combination therapy that can strengthen anticancer effects through a synergistic interaction between heat, chemotherapy and radiation. Here, we carried out a systematic review and meta-analysis to evaluate the clinical efficacy and safety of chemoradiation combined with regional hyperthermia (HCRT) for oesophageal carcinoma. METHODS: We conducted computer searches of foreign databases, including Cochrane Library, PubMed, EMBASE, Web of Science and Chinese databases, including CBM, CNKI and WanFang; we also retrieved other sources as supplement. All relevant randomized controlled trials (RCTs) were collected to compare HCRT and other therapies, including chemotherapy combined with radiotherapy (CRT) and radiotherapy alone (RT). After literature screening, data extraction and quality evaluation performed by appropriate criteria, the meta-analyses were conducted using RevMan 5.1 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). RESULTS AND DISCUSSION: Nineteen RCTs were included, comprising 1519 patients. Meta-analysis showed that the 1-, 3-, 5- and 7-year survival, complete response and total effective rates of the HCRT group were higher than those of the CRT group; the rates of gastrointestinal reaction, leucocytopenia and radiation oesophagitis in the HCRT group were lower than those of the CRT group, indicating significant differences (P < 0·05). The 1-, 2-, 3- and 5-year survival, complete response and total effective rates of the HCRT group were higher than those of the RT group, the recurrence and distant metastasis rates of the HCRT group were lower than those of the RT group, and there were significant differences in all of the indicators (P < 0·05). WHAT IS NEW AND CONCLUSIONS: This is the first systematic review and meta-analysis to evaluate HCRT for oesophageal carcinoma. Compared with CRT or RT, HCRT can improve long-term and short-term curative effects; it is also safe and feasible. Additional high-quality and large sample size RCTs will be necessary to further demonstrate the long-term survival benefits and comprehensive safety profile of HCRT.

Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study.

BACKGROUND: While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD). METHOD: Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾ 24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾ 50% MADRS score reduction) was the primary outcome. RESULTS: By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01-0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02-0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days-2 weeks; effect size (ES) = 1.08-1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation. CONCLUSIONS: Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.

A novel orthotopic mouse model of head and neck cancer and lymph node metastasis.

Prognosis of head and neck squamous cell carcinoma (HNSCC) is largely determined by the extent of lymph node (LN) metastasis at diagnosis, and this appears to be controlled by cancer cell genetics. To examine the role of these genes in LN metastasis, we created a human-in-mouse orthotopic model of HNSCC and performed comparative microarray analysis of gene expression between populations of HNSCC cell lines derived before and after serial transplantation and in vivo metastasis in mice. Microarray analysis comparing the USC-HN3-GFP, USC-HN3-GFP-G1 and USC-HN3-GFP-G2 cell lines identified overexpression of genes implicated in epithelial-to- mesenchymal transition and the formation of cancer stem cells, including CAV-1, TLR-4 (Toll-like receptor 4), MMP-7 (matrix metalloproteinase 7), ALDH1A3, OCT-4 and TRIM-29. Ingenuity Pathway Analysis confirmed upregulation of respective gene signaling pathways in the USC-HN1-GFP-G2 cell line. Patient HNSCC samples from advanced stages overexpressed ALDH1A3, CAV-1 and MMP-7. Our results show that CAV-1, TLR-4, MMP-7, ALDH1A3, OCT-4 and TRIM-29 have increased expression in HNSCC cells selected for an enhanced metastatic phenotype and suggest that these genes may have an important role in the metastatic potential of HNSCC cells. Inhibition of these genes may therefore have prognostic and therapeutic utility in HNSCC.

Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles.

The synergetic process of folliculogenesis is mainly regulated by GDF-9 and BMP-15 as well as their receptors, such as BMPR2, TßR1 and BMPR1B. Expressions of these factors and the receptors are significant different among species. This study was designed to detect expression of GDF-9, BMP-15 and their receptors in mouse, porcine and human healthy follicles by immunohistochemistry. Three ages of human ovary were studied according to ovarian developmental schedule, i.e. gestational week (GW) 16, puberty (14 year-old) and adult (40 year-old). The results showed that both GDF-9 and BMP-15 were detectable in oocytes from primary follicles onward, besides, BMP-15 also presented in granulosa cells (GCs) and follicular follicle of mature follicles in mouse. However, they were maintained in oocytes and GCs from primordial to mature follicles in porcine except that GDF-9 was undetectable in GCs of mature follicles. For human ovary, GDF-9 presented in oocytes of primordial follicles in all samples, whereas BMP-15 was only observed in primordial follicle of adult ovary. Receptors, BMPR2, TßR1 and BMPR1B were found in oocytes and GCs of all follicles in mouse and porcine. In human, they were stained in oocytes from primordial follices but BMPR1B was not expressed in pubertal primordial follicles. Furthermore, we found that GDF-9, BMP-15 and three receptors distributed in adult corpus lutea. Collectively, our studies suggested that GDF-9, BMP-15 and their receptors might correlate with primordial follicular recruitment in pig and human. Positive expression of the receptors (BMPR2, TßR1 and BMPR1B)in primordial follicles of mouse ovaries indicated that these receptors might interact with others ligands besides GDF-9 and BMP-15 to regulate primordial follicular activity in mouse. Moreover, presence of GDF-9 in oocytes and BMP-15 in oocytes and GCs of mature follicles from mice and porcine elucidated coordinated roles of GDF-9 and BMP-15 in cumulus oophorus expansion. Additionally, expression of these factors in adult human corpus lutea suggested they play roles in corpus luteum activity.

Ultrasound bone densitometry of the calcaneus in healthy Chinese children and adolescents.

INTRODUCTION: We evaluate reference data to examine whether there are sex-, age-, height-, weight- and BMI-related differences of quantitative ultrasound parameters (QUS) for healthy Chinese children and adolescents. METHODS: A total of 726 healthy children and adolescents (360 male and 366 female) aged from 10-21 years were examined with a Lunar Achilles Express densitometer. The measurements on the right heel included speed of sound (SOS), broadband ultrasound attenuation (BUA), and a calculated stiffness index (SI). RESULTS: Our results found that there were no significant differences for BUA, SOS and SI between males and females, except in the age range of 12 to 13 years. The values of all parameters were significantly higher in the 12-year-old females compared to males, and BUA values were significantly higher in 13-year-old females compared to males. A spurt in QUS parameters were observed at 12 years in females and at 14 years in males. A steady increase of BUA, SOS, and SI was seen with increasing body height and weight in both sexes. CONCLUSION: In conclusion, the present results can be used as reference data for children and adolescents in China.

Characteristics of calcaneus quantitative ultrasound normative data in Chinese mainland men and women.

INTRODUCTION: Quantitative ultrasound (QUS) assessment at the calcaneus, as a safe and reliable method for evaluating skeletal status, is rapidly gaining in popularity. Assessment by QUS provides three parameters of skeletal status: broadband ultrasound attenuation (BUA), speed of sound (SOS) and derived data-stiffness index (STI). The objective of the present study was firstly to determine the normative QUS data on healthy Chinese mainland men and women and secondly to investigate the effects of sex, age and body size on these three QUS parameters. METHODS: A study cohort consisting of 725 healthy Chinese women and 568 men aged 10-83 years participated in this investigation. The three QUS parameters all exhibited a characteristic mild rise-then-fall pattern with increasing age in both sexes. Younger men and women had similar QUS values, while older women had lower values than older men. Age-related differences were more pronounced among females. Pearson's correlation and regression analysis showed that weight was a major determinant of QUS in both sexes, along with age. RESULTS: There were some discrepancies between our data and results from other populations, even when the same type of QUS instrument was used, probably as a result of various factors, including ethnic, life-style environment and diet, among others. CONCLUSIONS: These normative data will be useful for comparing the results of individual studies, predicting fracture risk of Chinese men and women and determining diagnostic criteria of osteoporosis by QUS.

New modeling method and mechanism analyses for active control of interior noise in an irregular enclosure using piezoelectric actuators.

A new modeling method is developed in this paper for the active minimization of noise within a three-dimensional irregular enclosure using distributed lead zirconate titanate piezoelectric (PZT) actuators, and the control mechanisms for irregular enclosure are analyzed. The irregular enclosure is modeled with four rigid walls and two simply supported flexible panels, and PZT actuators are bound to one of the flexible panels. The process of the new modeling method is as follows. First, the modal coupling method is used to establish the motion equations, which contain important coefficients such as modal masses and modal coupling coefficients, etc., of acoustic-structural-piezoelectric coupling system. Then, the acoustic modes and the modal masses of irregular enclosure are calculated by numerical methods. Last, the modal coupling coefficients in motion equations are calculated according to the numerical results of the acoustic modes of irregular enclosure and the modes of two panels. The validity of this modeling method is verified by a regular hexahedron enclosure. Two cost functions are applied to this model. With the two cost functions, good results are obtained in minimizing the sound-pressure level (SPL) within irregular enclosure according to numerical investigations. By comparing the results obtained under controlled and uncontrolled states, the control mechanisms of the system are discussed. It is found that the control mechanisms vary with disturbance frequencies. At most disturbance frequencies, the SPL within enclosure is reduced by restructuring the modes of two panels simultaneously. When the disturbance frequency comes close to one of the natural frequencies of panel a, the dominant mode of panel a is suppressed, while the modes of panel b are reconstructed. While the disturbance frequency is near one of the natural frequencies of panel b, the modes of two panels are restructured at the same time.

Targeted diagnosis of bladder and ureteral carcinoma using radiolabelled BDI-1.

The aim of this study is to investigate the possibility of radioimmunoimaging (RII) by radiolabelled anti-bladder carcinoma monoclonal antibody BDI-1 applied to diagnosis of bladder cancer and ureteral cancer. BDI-1 was labelled with 131I and 99mTc. The immunoreactivity, pharmacokinetics and biodistribution in mice were studied. RII was performed in 46 patients. The results showed that 131I, 99mTc-BDI-1 have satisfactory immunoreactivity and excellent tumor-locating properties. The blood clearance half-life T1/2alpha and T1/2beta were 35 h in the first phase and 151 h in the second phase, respectively. Thirty-nine patients were studied by an intravesical administration method; the sensitivity was 90.5%. Seven patients were studied by an intravenous administration method. The RII results of three cases with primary or recurrent bladder cancer and three cases with ureteral cancer were confirmed histologically. RII was negative in one patient with suspected lung metastasis that was shown on radiography. The investigation revealed that RII can be used as an auxiliary method for the detection of bladder cancer and may be valuable for the diagnosis of ureteral cancer.

[K562 cells differentiation induced by RNA from rabbit reticulocytes].

OBJECTIVE: To study the effect of RNA from the reticulocytes of rabbit on cell differentiation of human leukemia cell line K562 cells. METHOD: RNA from rabbit reticulocytes and human leukemia K562 cells were cultured for 4 days to detect cellular changes. RESULTS: When K562 cells grew in a medium containing 100 micrograms/ml RNA, the cellular growth and division were gradually suppressed and the cells changed toward a differentiated phenotype. Subsequently, K562 cells produced hemoglobins and further differentiated terminally. CONCLUSION: RNA of mammalian erythrocyte played a role in declining cellular division and growth of K562 cells, reversing malignant phenotype, and promoting differentiation.

Seroepidemiologic study of Cryptosporidium infection in children from rural communities of Anhui, China and Fortaleza, Brazil.

A cluster-sampling, cross-sectional study was conducted for assessing the prevalence of Cryptosporidium infection in children less than 16 years of age from three villages, Dondian, Linshan, and Fuziyin, in rural Anhui in eastern China. Among 320 apparently healthy children less than 10 years of age from Dondian who had stool specimens collected, cryptosporidial oocysts were found in stools of three children from Dondian, and no positive specimens were found in 239 children studied from Linshan. In addition, a total of 610 serum samples from children in these three villages were tested for specific IgG antibody to Cryptosporidium with an enzyme-linked immunosorbent assay (ELISA) and the prevalence rates were 42.3%, 51.7%, and 57.5%, respectively, in Dondian, Linshan, and Fuziyin. Seroprevalence increased progressively with age. No detectable antibody was found in infants between two and six months of age, and seropositivity steadily increased after one year of age. Among 36 sera from adults 15-60 years of age without diarrheal illness in Huanglu villages of rural Chaohu, 50% (18 of 36) were positive. As expected, a good correlation was found in the specific IgG antibody between the paired serum specimens from 30 matched mother-neonates who showed transplacental transfer of IgG. However, little or no IgM antibody was seen in the neonates even though several mothers had a positive anticryptosporidial IgM enzyme-linked immunoassay result. Forty randomly selected serum samples from children less than four years of age in a similarly impoverished semiurban community in Fortaleza, Brazil, where the majority of households also have pit toilets and shared community water supplies and 172 serum samples from patients one month to 29 years of age admitted to the University of Virginia Hospital without diarrhea were also examined. In Fortaleza, almost all children acquired antibody by their second year of life, demonstrating the high prevalence of this infection. In rural Anhui, only about half the children were infected by 5-7 years of age. The overall prevalence rate (16.9%) of seropositivity among children and young adults in Virginia was much lower than in China and Brazil. These results indicate that cryptosporidial infection is ubiquitous, and is highly endemic in these impoverished communities. The difference between China and Brazil may reflect earlier weaning, hygiene practices, poorer water or sanitation, multiple siblings in family and geographic environment in Brazil.

Characterization of OhS1, an arginine/lysine amidase from the venom of king cobra (Ophiophagus hannah).

In this paper, we present the results of purification and characterization of an arginine/lysine amidase from the venom of Ophiophagus hannah (OhS1). It was purified by Sephadex G-75 gel filtration and ion-exchange chromatography on DEAE-Sepharose CL-6B. It is a protein of about 43,000, consisting of a single polypeptide chain. It is a minor component in the venom. The purified enzyme was capable of hydrolysing several tripeptidyl-p-nitroanilide substrates having either arginine or lysine as the C-terminal residue. We studied the kinetic parameters of OhS1 on six these chromogenic substrates. OhS1 did not clot fibrinogen. Electrophoresis of fibrinogen degraded with OhS1 revealed the disappearance of the alpha- and beta-chains and the appearance of lower mol. wt fragments. OhS1 had no hemorrhagic activity. It did not hydrolyse casein, nor did it act on blood coagulation factor X, prothrombin and plasminogen. The activity of OhS1 was completely inhibited by NPGB, PMSF, DFP, benzamidine and soybean trypsin inhibitor, suggesting it is a serine protease. Metal chelator (EDTA) had no effect on it.

Household epidemiology of Cryptosporidium parvum infection in an urban community in northeast Brazil.

OBJECTIVE: To examine the transmission of Cryptosporidium infection in households with an identified person with cryptosporidiosis. DESIGN: Prospective cohort study. SETTING: An urban slum in Fortaleza, Brazil. PARTICIPANTS: Thirty-one households with a child less than 3 years of age (index case) who was positive for Cryptosporidium parvum using acid-fast and auramine-stained stool smears. MEASUREMENTS: Three stool samples (at 0, 2, and 6 weeks after identification of the index case) and two serum samples (0 and 6 weeks) were collected from each family member in households with an index case of Cryptosporidium infection. RESULTS: Forty-five percent of index cases of Cryptosporidium infection were associated with persistent (> 14 days) diarrhea. Secondary cases of Cryptosporidium infection were identified either by stool examination or seroconversion in 18 (58%) of 31 households involving 30 persons, yielding an overall transmission rate of 19%. Of the 202 persons in this study with at least one serum sample available for analysis, 191 (94.6%) had evidence of antibodies (either IgM or IgG) to Cryptosporidium. CONCLUSIONS: Cryptosporidium parvum is highly transmissible and infective in the family setting, with transmission rates similar to other highly infectious enteric pathogens such as Shigella species. These data are cause for added concern because of the rapidly increasing rate of seropositivity for human immunodeficiency virus.

PIP: Between December 1990 and April 1992 investigators enrolled 31 households with a less than 3-year-old child infected with Cryptosporidium parvum in a prospective cohort study to determine the infectivity of Cryptosporidium parvum in families living in crowded conditions, mainly in the Goncalves Dias slum in Fortaleza, Brazil. The median household size was 7. The median age of the 33 index cases was 11 months, while the median age of the 192 family contacts was 21 years. 94% of the index cases had diarrhea at the time Cryptosporidium infection was diagnosed. 45% of the index cases had persistent diarrhea ( 14 days). The median duration of diarrhea was 14 days (range, 1-84 days). Most index cases (83%) had at least 1 other positive stool test for Cryptosporidium. Just 1 index case shed oocysts for 6 weeks. Index cases transmitted Cryptosporidium infection to 30 (19%) of 182 household contacts as evidenced by either a positive stool examination or seroconversion. These 30 secondary cases were from 18 of the 31 households. Only 8 (27%) secondary cases had diarrhea and 25% of them had persistent diarrhea, suggesting preexisting protective immunity in this area where Cryptosporidium infection is endemic. Household contacts who were 5 years old or younger were significantly more likely to have been diagnosed with Cryptosporidium than were those older than 5 years (30% vs. 5%; p 0.001). Most persons with at least 1 serum sample available for analysis (191/202 = 94.6%) had antibodies (IgM or IgG) to Cryptosporidium. The high rate of transmission of Cryptosporidium in this population, the serious threat of persistent diarrhea among young children, and the ever increasing rate of HIV transmission in Brazil (especially among slum dwellers with no access to condoms and to education about AIDS) should raise great concern.

Cryptosporidium parvum infection of intestinal epithelium: morphologic and functional studies in an in vitro model.

A monolayer of mature polarized colonic epithelial cells (T84) able to generate and maintain a barrier to macromolecular flow was used to study pathophysiologic events that occur on microvillus cell exposure to Cryptosporidium parvum. By 24-48 h, several life cycle forms were seen in parasitophorous vacuoles near the apical cell surface, along with a time- and oocyst dose-dependent reduction in epithelial barrier function. As few as 10(5) organisms constituted a successful infecting dose, and heat inactivation of organisms markedly reduced the monolayer barrier alteration. Horseradish peroxidase flux studies demonstrated a substantial increase in macromolecular permeability of the monolayer, and lactate dehydrogenase determinations indicated modest injury of the T84 epithelial cells on exposure to oocysts. Thus, disruption of the epithelial cell barrier, not just opening of transcellular channels for ion flow as reported previously, is responsible for the effects of C. parvum oocysts on intestinal epithelium.

Cryptosporidiosis: Pathogenesis and immunology.

Cryptosporidium parvum is an increasingly recognized agent of intestinal infection in normal and immunocompromised humans, and in many other animals. The intraepithelial cell infection results in villous atrophy, mild submucosal inflammation, reduction of brush-border enzymes and a characteristic persistent watery diarrhea. The infection is self-limiting in immunocompetent hosts, probably because of specific acquired immunity; specific serum and secretory antibody responses develop that may be required for clearance and protection against reinfection. Passive milk antibody, especially i f in high titers, may be partially protective but severe, persistent infection in athymic rodents and humans with AIDS demonstrate that T cells are essential for controlling the infection. Specific anti-bodies and lymphocyte extracts have been tested in cases of cryptosporidiosis but the interpretation of the results remains controversial. Here, Shu-Xian Zu, Guo-Dong Fang, Ronald Foyer and Richard Guerrant emphasize that effective treatment and prevention remain dependent on advances in our understanding of the host cell-parasite relationship.

Cancer mortality and mortality trends in Henan, China, 1974-1985.

Promotion of cancer control programs requires accurate data on cancer incidence and mortality from population-based cancer registries. Currently, there are 12 institutions that register cancer deaths in the respective 12 counties and cities. The data thus obtained show that cancer of the esophagus, stomach, and liver in both sexes and cervical cancer in females are the leading causes of all cancer deaths. During the period of 1974-1985, marked changes have taken place in the Henan province in cancer mortality rates of certain sites. Some description and discussion of these changes are presented in this paper.