Retrospective study on prognostic importance of serum procalcitonin and amino‑terminal pro‑brain natriuretic peptide levels as compared to Acute Physiology and Chronic Health Evaluation IV Score on Intensive Care Unit admission, in a mixed Intensive Care Unit population.

Background: Timely decision making in Intensive Care Unit (ICU) is very essential to improve the outcome of critically sick patients. Conventional scores like Acute Physiology and Chronic Health Evaluation (APACHE IV) are quite cumbersome with calculations and take minimum 24 hours. Procalcitonin has shown to have prognostic value in ICU/Emergency department (ED) in disease states like pneumonia, sepsis etc. NTproBNP has demonstrated excellent diagnostic and prognostic importance in cardiac diseases. It has also been found elevated in non-cardiac diseases. We chose to study the prognostic utility of these markers on ICU admission. Settings and Design: Retrospective observational study. Materials and Methods: A Retrospective analysis of 100 eligible patients was done who had undergone PCT and NTproBNP measurements on ICU admission. Their correlations with all cause mortality, length of hospital stay, need for ventilator support, need for vasopressors were performed. Results: Among 100 randomly selected ICU patients, 28 were non-survivors. NTproBNP values on admission significantly correlated with all cause mortality (P = 0.036, AUC = 0.643) and morbidity (P = 0.000, AUC = 0.763), comparable to that of APACHE-IV score. PCT values on admission did not show significant association with mortality, but correlated well with morbidity and prolonged hospital length of stay (AUC = 0.616, P = 0.045). Conclusion: The current study demonstrated a good predictive value of NTproBNP, in terms of mortality and morbidity comparable to that of APACHE-IV score. Procalcitonin, however, was found to have doubtful prognostic importance. These findings need to be confirmed in a prospective larger study.

The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy

Hepatocellular carcinoma (HCC) is a primary concern for patients with chronic hepatitis B (CHB). Antiviral therapy has been reasonably the focus of interest for HCC prevention, with most studies reporting on the role of the chronologically preceding agents, interferon-alfa and lamivudine. The impact of interferon-alfa on the incidence of HCC is clearer in Asian patients and those with compensated cirrhosis, as several meta-analyses have consistently shown HCC risk reduction, compared to untreated patients. Nucleos(t)ide analogues also seem to have a favorable impact on the HCC incidence when data from randomized or matched controlled studies are considered. Given that the high-genetic barrier agents, entecavir and tenofovir, are mainly used in CHB because of their favorable effects on the overall long-term outcome of such patients, the most clinically important challenge is the identification of patients who require close HCC surveillance despite on-therapy virological remission. Several risk scores have been developed for HCC prediction in CHB patients. Most of them, such as GAG-HCC, CU-HCC and REACH-B, have been developed and validated in Asian untreated and treated CHB patients, but they do not seem to offer good predictability in Caucasian CHB patients for whom a newer score, PAGE-B, has been recently developed.

Isolated free intra-abdominal fluid on CT in blunt trauma: The continued diagnostic dilemma / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>The clinical significance of isolated free fluid (FF) without solid organ injury on computed to- mography (CT) continues to pose significant dilemma in the management of patients with blunt abdominal trauma (BAT).</p><p><b>METHODS</b>We reviewed the incidence of FF and the clinical outcome amongst patients with blunt abdominal trauma in a metropolitan trauma service in South Africa. We performed a retrospective study of 121 consecutive CT scans over a period of 12 months to determine the incidence of isolated FF and the clinical outcome of patients managed in a large metropolitan trauma service.</p><p><b>RESULTS</b>Of the 121 CTs, FF was identified in 36 patients (30%). Seven patients (6%) had isolated FF. Of the 29 patients who had free fluid and associated organ injuries, 33 organ injuries were identified. 86% (25/ 29) of all 29 patients had a single organ injury and 14% had multiple organ injuries. There were 26 solid organ injuries and 7 hollow organ injuries. The 33 organs injured were: spleen, 12; liver, 8; kidney, 5; pancreas, 2; small bowel, 4; duodenum, 1. Six (21%) patients required operative management for small bowel perforations in 4 cases and pancreatic tail injury in 2 cases. All 7 patients with isolated FF were initially observed, and 3 (43%) were eventually subjected to operative intervention. They were found to have an intra-peritoneal bladder rupture in 1 case, a non-expanding zone 3 haematoma in 1 case, and a negative laparotomy in 1 case. Four (57%) patients were successfully managed without surgical interventions.</p><p><b>CONCLUSIONS</b>Isolated FF is uncommon and the clinical significance remains unclear. Provided that reli- able serial physical examination can be performed by experienced surgeons, an initial non-operative approach should be considered.</p>

Pristimerin enhances recombinant adeno-associated virus vector-mediated transgene expression in human cell lines in vitro and murine hepatocytes in vivo / 中西医结合学报

<p><b>OBJECTIVE</b>In the present study, we systemically evaluated the ability of two bioactive compounds from traditional Chinese medicine, celastrol and pristimerin, to enhance recombinant adeno-associated virus (rAAV) serotype vector-mediated transgene expression both in human cell lines in vitro, and in murine hepatocytes in vivo.</p><p><b>METHODS</b>Human cell lines were infected with rAAV vectors with either mock treatment or treatment with celastrol or pristimerin. The transgene expression, percentage of nuclear translocated viral genomes and the ubiquitination of intracellular proteins were investigated post-treatment. In addition, nonobese diabetic/severe combined immunodeficient gamma (NSG) mice were tail vain-injected with rAAV vectors and co-administered with either dimethyl sulfoxide, celastrol, pristimerin or a positive control, bortezomib. The transgene expression in liver was detected and compared over time.</p><p><b>RESULTS</b>We observed that treatment with pristimerin, at as low as 1 μmol/L concentration, significantly enhanced rAAV2 vector-mediated transgene expression in vitro, and intraperitoneal co-administration with pristimerin at 4 mg/(kg·d) for 3 d dramatically facilitated viral transduction in murine hepatocytes in vivo. The transduction efficiency of the tyrosine-mutant rAAV2 vectors as well as that of rAAV8 vectors carrying oversized transgene cassette was also augmented significantly by pristimerin. The underlying molecular mechanisms by which pristimerin mediated the observed increase in the transduction efficiency of rAAV vectors include both inhibition of proteasomal degradation of the intracellular proteins and enhanced nuclear translocation of the vector genomes.</p><p><b>CONCLUSION</b>These studies suggest the potential beneficial use of pristimerin and pristimerin-containing herb extract in future liver-targeted gene therapy with rAAV vectors.</p>

Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo / 中西医结合学报

<p><b>OBJECTIVE</b>Little effort has been made to study the protein-encoding genes isolated from traditional Chinese medicine (TCM) drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated virus (rAAV) vectors has not been attempted.</p><p><b>METHODS</b>We synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The protein expression was confirmed by Western blot assay. Various cancer cell lines were transfected with the above plasmids and cell growth was monitored both in vitro and in vivo. The best cytotoxic gene was further packaged into rAAV vectors, under the control of a liver cancer-specific promoter. The liver tumor growth was then monitored following intratumor administration of the rAAV vectors.</p><p><b>RESULTS</b>The expression plasmids, encoding individual potential cytotoxic genes tagged with FLAG epitope, were successfully generated and sequenced. Among these genes, trichosanthin (TCS) gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome-inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Furthermore, intratumor injection of rAAV vectors containing the TCS gene significantly inhibited the growth of human hepatocellular carcinoma tumors in a murine xenograft model.</p><p><b>CONCLUSION</b>Our studies suggest that the use of TCM cytotoxic genes is a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular.</p>

Age-dependent dichotomous effect of superoxide dismutase Ala16Val polymorphism on oxidized LDL levels

We investigated the association between superoxide dismutase (SOD) Ala16Val polymorphism and the levels of oxidized LDL lipoprotein-C (ox-LDL-C) in two age-different Greek cohorts. Four hundred fifteen middle-aged (n=147 females: 43.2+/-13 years, n=268 males: 43.3+/-14 years) Caucasian Greek subjects consisted the middle aged cohort. One hundred seventy five elderly (n=88 females: 79.9+/-4 years; n=87 males: 80.6+/-4 years) were selected from the elderly cohort. Genotype data were obtained for all of them. Multiple linear regression analysis, stratified by gender and adjusted for age, smoking habits and body mass index as covariates, showed higher ox-LDL-C levels for the middle aged men with the Val/Val genotype, compared to the other allele (Ala/Ala and Ala/Val) carriers (65.9+/-25.7 vs. 55.7+/-20.5 mg/dl; standardized beta coefficient=0.192, P=0.012). On the contrary, elderly women with the Val/Val genotype occurred with lower ox-LDL-C levels compared to the Ala/Ala or Ala/Val genotype (74.2+/-22.1 vs. 86.5+/-26.6 mg/dl; standardized beta coefficient= -0.269, P=0.015). The same trend was also recorded in elderly men, however without reaching statistical significance (standardized b coefficient= -0.187, P=0.077). Moreover, elderly men and women with the Ala/Ala or Ala/Val genotype presented higher triglycerides levels compared to Val/Val (women: 145.2+/-68.7 vs. 114.3+/-34.3 mg/dl, P= 0.027; men: 147.8+/-72.4 vs. 103.7 +/-38.0 mg/dl, P=0.002). Additionally, middle aged men with the Val/Val genotype had higher HDL-C levels compared to the Ala allele carriers. The results suggest that SOD Ala16Val polymorphism is an age-dependent modulator of ox-LDL-C levels in middle-aged men and elderly women.

The rapid diagnosis of HIV-1 infection in mothers in Puerto Rico: a crucial testing strategy for maximal reduction of perinatal transmission

This study was designed to evaluate early post partum rapid HIV testing of infants as surrogates for their mothers. In a screening of 971 infants whose mother's HIV-1 status was not known at delivery, 22 (= 2.26) were found positive for antibodies by ELISA. Five were new cases and two (40) were from transmitting mothers. This is in contrast with the UPR Women and Infants Transmission Study (UPR WITS) in which of 186 HIV-1 infected mothers none were transmitters. These were selected among thousands screened for anti-HIV-1 antibodies over a period of almost 5 years studied (September, 1996 through August, 2001). These results clearly indicate that all mothers at delivery should have a rapid test to determine their HIV-1 status to allow in the positive cases rapid intervention strategies to prevent perinatal transmission.

Seroprevalence of Schistosoma mansoni in Puerto Ricans with inflammatory bowel disease

BACKGROUND: The etiology of Inflammatory Bowel Diseases, Crohn's disease (CD) and ulcerative colitis (UC), is unknown. These diseases have a higher incidence in industrialized countries and their pathogenesis involves an over-reaction of the immune system. A genetic factor is believed to predispose to the development of chronic inflammation in response to an unidentified stimulus. Exposure to infections in childhood may modulate future immune responses. Parasitosis, particularly Schistosomiasis, stimulate Th2 immune responses. It has been hypothesized that the absence of these parasitic infections, as seen in economically developed countries, favors a Th1 response that may result in the clinical appearance of Crohn's disease later in life. OBJECTIVE: To determine the prevalence of Schistosoma mansoni antibodies in Puerto Ricans with Inflammatory Bowel Disease and controls. METHODS: Serum from 92 Puerto Ricans with IBD and 106 controls was screened for S. mansoni adult microsomal antigens (MAMA) using the FAST:ELISA assay. Those positive were confirmed with an enzyme-linked immunoelectrotransfer blot test. RESULTS: Seven serum samples (3 UC and 4 controls) were positive for S. mansoni antibodies. There was no significant difference between groups in gender, municipality of origin or seroprevalence of Schistosomiasis. The control group was slightly older than the IBD group. CONCLUSIONS: Our study did not demonstrate an inverse relation between Schistosomiasis and IBD. However, the decreasing prevalence of Schistosomiasis in the general population of Puerto Rico may account for this result.

Acinetobacter meningitis following head trauma.

A case of acinetobacter meningitis following head injury in a patient who developed cerebrospinal fluid otorrhea, and did not have any neurosurgical procedure, is presented. Previously reported cases are cited, with a review of the literature. Pefloxacin monotherapy is associated with a poor clinical response.

CAMP test for the identification of Vibrio cholerae 0139.

The confirmation of the identity of Vibrio cholerae serogroup 01 and serogroup 0139 is usually done by slide agglutination tests using specific antisera. Antiserum to V. cholerae 01 is freely available but not antiserum to V. cholerae 0139, thus making specific identification of the latter more difficult. A modified CAMP (Christie Atkins and Muench - Paterson) test has been described as a possibility in the identification of V. cholerae 0139 and we have evaluated this on 197 strains of organisms including 48 V. cholerae 0139, 50 V. cholerae 01, 49 non-01, non-139 V. cholerae and 50 Aeromonas species. The test had a sensitivity of 98.9 per cent and a specificity of 92.9 per cent in the identification of these strains, when compared with faeces culture as the gold standard.

Comparison of purified 12 kDa and recombinant 15 kDa Fasciola hepatica antigens related to a Schistosoma mansoni fatty acid binding protein

Vaccines in schistosomiasis using homologous antigens have been studied extensively in experimentally infected mammalian hosts. Vaccines using heterologous antigens have received comparatively less attention. This review summarizes recent work on a heterologous 12 kDa Fasciola hepatica antigenic polypeptide which cross reacts with Schistosoma mansoni. A cDNA has been cloned and sequenced, and the predicted amino acid sequence of the recombinant protein has been shown to have significant (44) identity with a 14 kDa S. mansoni fatty acid binding protein. Thus in the parasitic trematodes fatty acid binding proteins may be potential vaccine candidates. The F. hepatica recombinant protein has been overexpressed and purified and denoted rFh15. Preliminary rFh15 migrates more slowly (i.e. may be slightly larger) than nFh12 on SDS-PAGE and has a predicted pI of 6.01 vs. observed pI of 5.45. Mice infected with F. hepatica develop antibodies to nFh12 by 2 weeks of infection vs. 6 weeks of infection to rFh15; on the other hand, mice with schistosomiasis mansoni develop antibodies to both nFh12 and rFh15 by 6 weeks of infection. Both the F. hepatica and S. mansoni cross-reactive antigens may be cross-protective antigens with the protection inducing capability against both species.

Identification of gram positive cocci isolated from urine.

A total of 195 strains of Gram positive cocci isolated from urine, in pure culture and in counts of > 10(3) colony forming units/ml, during January-September 1992, were speciated using schema recently described by Facklam and Washington, and Kloos and Lambe. Seventy three (85%) of the 86 enterococci were identified as Enterococcus faecalis while 11 (13%) were E. faecium. Eighteen (29%) of the 62 staphylococcal isolates were Staphylococcus aureus; 20 (45%) of the 44 coagulase negative staphylococci were speciated as Staph. haemolyticus. Of the 47 strains of beta haemolytic streptococci isolated, 45 (96%) were group B; one was group G and the other group F. Our results show the diverse species of Gram positive cocci associated with bacteriuria and the need to speciate them in a diagnostic laboratory. In the context of a larger number of tests required for the speciation of Gram positive cocci, we recommend a simplified scheme which we found feasible on a routine basis.

Evaluation of an elisa for the diagnosis of human infection with S haematobium

ShSEA prepared from eggs collected from urine samples of infected humans and SmSEA prepared from eggs collected from infected hamsters were tested in and ELISA against 226 human sera classified into four groups: 30 normal controls, 82 S. mansoni infected, 64 S. haematobium infected and 50 with concurrent infection with both species. ELISA proved to be efficient diagnostic test for schistosomiasis giving 98- 100% sensitivity, but low species specificity, 23-28%. However, the mean absorbance value of S. haematobium infection sera was significantly higher with homologous than heterologous antigens which indicate the presence of S. haematobium species-specific antigens

Prevalence of intestinal parasites in a rural community in north-central Puerto Rico

Se realizó un estudio hematológico y parasitológico en Bayaney, Hatillo, una comunidad rural localizada en la parte norte-central de Puerto Rico. Un hallazgo sorprendente fue la alta proporción comparativa de casos de eosinofilia encontrados (43 de 83; 52%). De estos 83 casos, 16 resultaron positivos para parásitos intestinales utilizando el método de concentración (Formol-Ether) Ritchie. Con eosinofilia de 5 a 10%, sen encontró infección con un parásito intestinal en 35% de los casos, con eosinofilia mayor de 10%, el 75% de los casos estaban infectados con un parásito intestinal. Los parásitos o larvas encontrados fueron: Uncinaria (N=8), Stronglyoides Stercoralis (N=2), Trichuris Trichiura (N=5) y un caso con una infección combinada de uncinaria y trichuris. Quince de estos 16 (94%) casos con parásitos intestinales tenían eosinofilia de 5 a 40%. De un subgrupo de niños de quinto grado de escuela, 11 de 35 (31%) tenían eosinofilia de 5 a 17%, pero solo dos de estos tenían huevos de parásitos (Trichuris). No se encontraron protozoos intestinales, a pesar de que todos los casos infectados estaban aparentemente asintomáticos, se les informó del resultado del estudio y en aquellos casos necesarios se les suplió examen médico y tratamiento. Se estudió la presencia de anticuerpos contra el huevo de S. mansoni por ELISA, usando una fracción de antígeno cationico llamado CEF-6. De 44 sueros analizados, 20 eran de un grupo de alto riesgo debido al contacto frecuente con agua infectada. Por serología solo un caso (2%) fue positivo y en este, el examen de excreta para huevos de S. mansoni fue negativo. Se necesitan estudios adicionales para determinar la etiología de eosinofilia en ausencia de infección por parásitos intestinales