Deferoxamine administration in septic animals: improved survival and altered apoptotic gene expression

BACKGROUND: Oxidative damage is one of the major factors that lead to cell damage, organ dysfunction and death in sepsis. Thus, an attractive candidate for the pharmacologic treatment of the septic syndrome is desferoxamine (DFX), an antioxidant iron chelator used for the removal of iron and a potential free radical scavenger. OBJECTIVE: The impact of DFX administration on the survival of septic animals. The effect on cell integrity and cycle of vital organs. METHODS: Sepsis was induced in 40 rats using the cecal ligation and puncture method (CLP) and 20 rats randomly received twice subcutaneously DFX (total dose: 40 mg/kg). Rats were monitored for 36 h and all vital organs were harvested for pathology examination and immunohistochemical detection of Bax, Bcl-2, cytochrome c and caspase-8 apoptosis regulating proteins. RESULTS: Mean survival in the DFX group was 34.2 h (median 36.0, S.D. 4.4) and 30.2 h (median 36.0, S.D. 9.1) in the control group (p=0.04), while 36 h after follow up 85% of the DFX-treated rats and 55% of placebo rats were alive (p=0.04). Expression of pro-apoptotic bax protein was significantly increased in the heart, liver and kidney of animals in the DFX group compared to the control group. CONCLUSIONS: Treatment with the polymeric iron chelator DFX significantly increases survival of septic subjects and alters the expression of bax, an apoptosis regulating protein in certain organs (heart, liver and kidney).     

Significance of lymphoblasts in cerebrospinal fluid in newly diagnosed pediatric acute lymphoblastic malignancies with bone marrow involvement: Possible benefit of dexamethasone

We analyzed retrospectively the data on 135 children treated since 1983 for acute lymphoblastic leukaemia and non-Hodgkin's lymphoma with bone marrow involvement with respect to the presence of lymphoblasts in cerebrospinal fluid (CSF) and the number of cells in CSF, both at initial diagnosis and during follow-up. Of these children 96, 11, and 28 suffered from B-progenitor, mature B-cell, and T-cell malignancies, respectively. In two patients initial central nervous system involvement was documented by the presence of lymphoblasts with high CSF cell counts (B+C+ patients); 19 patients had CSF lymphoblasts with normal CSF cell counts (B+C? patients); the others had no CSF blasts and normal CSF cell counts (B-C- patients). In B+C? and B-C- patients 5-year-leukaemia-free survival was 66 and 70%, respectively (i.e., not significantly different). None of the B+C? patients experienced a first relapse in the central nervous system. Differences in outcome by comparing with reports of others may be related to the use of dexamethasone instead of prednisone in almost all of our patients. © 1995 Wiley-Liss, Inc.     

Functional evidence from microcell-mediated chromosome transfer of myeloid leukemia suppressor genes on human chromosomes 7 and 11

The long arm of human chromosome 7 between 7q22 and 7q36 has been identified as a region harboring one or more tumor-suppressor genes (TSGs) inactivated in acute myeloid leukemia (AML). Additional TSGs mapping to other chromosomes may well be involved in the etiology of this disease. For example, experiments using a mouse model system have indicated the possible presence of an AML TSG at 11p11-12. Microcell-mediated chromosome transfer (MMCT) has been used to introduce human chromosomes 7 and 11 into a murine myeloid leukemia cell line. A proportion of MMCT hybrid clones containing either whole chromosome 7 or fragments of chromosome 11 showed a significant delay in leukemogenic onset when injected into syngeneic mice. Screening of hybrid clones did not associate any human microsatellite markers with decreased leukemogenic potential in vivo. However, preliminary evidence was obtained of allelic loss at chromosomal regions homologous with human 7q22 in murine F1 hybrid AMLs. Our data provide functional evidence of AML-associated TSGs localized to human chromosomes 7 and 11 in support of previously published studies on cytogenetic and allelic losses associated with AML development.     

Lay theories of etiology and “cure” for four types of paraphilia: Fetishism; pedophilia; sexual sadism; and voyeurism

The current study set out to investigate the structure, determinants, and relationship between lay theories of the etiology and efficacy of “cures” for four types of paraphilia: fetishism, pedophilia, sexual sadism, and voyeurism. One hundred and five participants completed a four-part questionnaire, which was divided into (a) demographic details, (b) perceptions of the etiology, (c) ratings of cure for each paraphilia, and (d) the Eysenck Personality Questionnaire. Previous studies of lay theories have demonstrated a clear and interpretable factor structure similar to that of explicit academic theories, as well as a clear and logical relationship between perceived etiology and cure. A similar structure was expected to emerge in this study, together with positive correlations between the various factors and personality type. A factor analysis revealed a clear and logical factor structure for etiology and cure items. Further, etiology and cure factors correlated strongly with each other but only moderately with demographic details and personality differences. These findings are discussed in relation to growing literature in the field. © 1998 John Wiley & Sons, Inc. J Clin Psychol 54: 689–700, 1998.     

CVP and PAoP measurements are discordant during fluid therapy after traumatic brain injury

The objective of the study was to compare measurements of central venous pressure (CVP) and pulmonary artery occlusion pressures (PAoP) as estimates of intravascular volume during the first 96 hours of fluid therapy after traumatic brain injury (TBI). One thousand five hundred ten simultaneous CVP and PAoP measurements from 31 patients entered into the National Acute Brain Injury Study: Hypothermia (NABISH:H) protocol were retrospectively compared. The effect of fluid administration and body temperature upon the paired measurements was statistically assessed. Agreement between CVP and PAoP values was poor. The CVP and PAoP were equal in only 11% of paired values. The CVP was always higher than PAoP in 1 patient, whereas PAoP always exceeded the CVP in 5 others. In 74% of the pairs, the PAoP was higher than the CVP, whereas in 15%, CVP was greater than PAoP. For any CVP measurement, the PAoP was either 3 mm Hg above or below the CVP in 67% of the pairs and at least 5 mm Hg above or below the CVP in 21% of the pairs. In 21 (68%) patients, PAoP was > or = 5 mm Hg above CVP in more than 4 readings, a clinically important difference. Discordance was not attributed to the fluid administered or to the temperature protocol. Neurological outcome appears affected by the volume of fluid administration. However, during initial therapy, estimates of intravascular volume provided by the CVP and PAoP are discordant. Although documented in other clinical conditions, the disparity noted here after TBI has not been previously reported. Assessment of intravascular volume to avoid hypovolemia should utilize other measurement techniques.     

Characterization of rotavirus infection in a hospital neonatal unit in Pretoria,South Africa

Rotavirus infection in neonates is common and has been reported to be generally asymptomatic. In this longitudinal study, specimens were collected from 114 newborns in the Neonatal Unit at Pretoria Academic Hospital on a daily basis between January and May 1997. The babies remained in the ward between 1 week and 4 months. The stool specimens or rectal swabs were analysed for the presence of rotavirus antigen using a commercial enzyme-linked immunosorbent assay (Dako Rotavirus EIA) or electron microscopy. In total, 80 (70 per cent) of the neonates excreted rotavirus during their stay in the unit. There was a direct correlation between the length of stay in the ward and the shedding of rotavirus. The babies excreted rotavirus on average between 2 and 7 days. Rotavirus infection tended to occur within the first 2 weeks of life and was only observed once in most babies. Polyacrylamide gel electrophoresis of the RNA revealed the presence of two strains of rotavirus, with the differences in the RNA electropherotype occurring in the RNA segment triplet 7, 8 and 9. The VP7 serotype of the virus is encoded by one of these genes, and so the VP7 serotype of the virus was determined by monoclonal antibody and RT-PCR using VP7 serotype specific primers. The VP4 genotype of the viruses was also determined using RT-PCR of the VP4 gene to determine if a new rotavirus had been introduced to the ward. The strains were all characterized as G4P[6], which is similar to the antigenic make-up of the virus recovered 10 years before. This highlights the remarkable stability of rotavirus strains in neonatal units over long periods of time.     

Clinical utility of emerging biomarkers in prostate cancer liquid biopsies

ABSTRACT

Introduction: Prostate cancer (PCa) is one of the most common malignancies in men and a major cause of cancer deaths among men worldwide. Prostate specific antigen (PSA) monitoring and histopathological examination of tumor biopsies remain gold standards in PCa diagnostics. These clinical parameters are not well suited for patient stratification, predicting and monitoring treatment response. On the other hand, liquid biopsies offer a unique opportunity to easily isolate tumor-derived material for longitudinal clinical assessment.

Areas covered: In this review we focus on the clinical application of novel liquid biomarkers that have the potential to monitor and stratify patients in order to achieve better therapeutic effects and improve clinical outcomes. Enumeration and characterization of circulating tumor cells (CTCs), tumor-educated platelets, exosomes, and cell-free nucleic acids have been studied for their clinical utility in PCa diagnostics, prognostics, monitoring treatment response and guiding treatment choice.

Expert opinion: Liquid biomarkers have high potential to be used for prognosis, monitoring treatment response and guiding treatment selection. Although there is a remarkable progress in PCa biomarker discovery, their clinical validation is very limited. Research should be focused on biomarker validation and the incorporation of these biomarkers in clinical practice.     

Beyond the Pfannenstiel: Minimally invasive Laparotomy Incisions for Maximum Exposure

Although gynaecologists may be most familiar with the Pfannenstiel and midline laparotomy incisions, the Cherney and Maylard incisions are two alternative transverse abdominal incisions with unique advantages. Both provide superior pelvic exposure compared with the Pfannenstiel incision and offer significant benefits over a midline incision, such as decreased postoperative pain and improved wound healing. These incisions can be used for a multi-fibroid uterus, large pelvic masses, endometriosis, or when access to the retropubic or other pelvic spaces is needed. This video reviews surgically relevant anatomy of the anterior abdominal wall and provides a stepwise approach for performing both the Maylard and Cherney incisions using narrated illustrations and video footage. Surgical technique and anatomical considerations are highlighted throughout the video. This educational tool can be used as a reference for gynaecologists when performing these less commonly used incisions. When a laparotomy is indicated, the Maylard or Cherney incision can be considered as alternative approaches to a midline laparotomy in gynaecologic surgery, as both result in less postoperative morbidity while still providing excellent pelvic access.