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P Henschke

Publications and source records attributed to P Henschke.

15 recordsLinked to original sources
PubMed2001

Interleukin-6 and interleukin-8 in newborn bacterial infection.

The objective of this study is to determine the plasma concentrations and diagnostic accuracy of interleukin-6 (IL-6) and interleukin-8 (IL-8) in newborn infection. One hundred and one newborn infants with clinical signs of infection during their primary hospitalization were investigated with the minimum of a blood culture, C-reactive protein (CRP), full blood examination (FBE), and cytokine concentrations (IL-6 and IL-8). Infection in infants was classified without knowledge of cytokine levels into four groups-definite (n = 11), probable (n = 12), uncertain (n = 52), and nil (n = 26). The median concentrations of IL-6 and IL-8 were significantly higher in the definitely infected group compared with the other three groups (p <0.05). At the cut-off concentration of highest accuracy, IL-6 (>175 pg/mL) and IL-8 (>28 pg/mL) had similar sensitivities (80 and 82%, respectively) and specificities (91 and 81%, respectively). Cut-off concentrations could be identified with improved sensitivities (90% for IL-6 and 100% for IL-8) that maintained specificity >50%. However, the confidence intervals were wide for all sensitivities and specificities. IL-6 and IL-8 had little diagnostic accuracy in infants with probable infection. IL-6 and IL-8 concentrations increase early in newborn infants with definite infection.

C-Reactive Protein↗
PubMed2000

Metabolites of the biocide o-phenylphenol generate oxidative DNA lesions in V 79 cells.

Incubation of the o-phenylphenol (OPP) metabolites, o-phenylhydroquinone (PHQ) and o-phenylbenzoquinone (PBQ) with V 79 Chinese hamster cells led to a significant enhancement of the amount of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in nuclear DNA. With OPP no distinct induction of this lesion could be observed. In addition, PHQ and PBQ were able to generate DNA single-strand breaks (DNA SSB), while OPP failed to induce this lesion. All incubations were performed for 1 h without exogenous metabolic activations and the lowest effective concentration tested was 20 microM. It is concluded that these metabolites may contribute to the carcinogenicity of OPP and sodium o-phenylphenolate (SOPP) observed in rats, by generating reactive oxygen species (ROS) through their redox cycling properties.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Randomised, controlled trial of nasal continuous positive airway pressure in the extubation of infants weighing 600 to 1250 g.

AIM: To determine whether extubation to nasal continuous airway pressure (NCPAP) results in a greater proportion of infants remaining free of additional ventilatory support for one week after extubation compared with those extubated directly to headbox oxygen. METHODS: A randomised, controlled, clinical trial was conducted at the neonatal intensive care unit of the Royal Women's Hospital, Melbourne, of infants with birthweights between 600 and 1250 g, ventilated via an endotracheal tube for more than 12 hours, requiring less than 50% oxygen, a ventilator rate < or = 20/minute, considered by the clinical management team to be ready for extubation. Infants were randomly allocated either to NCPAP or to oxygen administered via a headbox. Success was defined by no requirement for additional ventilatory support over the week following extubation. Failure criteria were (i) apnoea; (ii) absolute increase in oxygen requirement greater than 15% above than required before extubation; or (iii) respiratory acidosis (pH < 7.25 with pCO2 > 6.67 kPa). RESULTS: Thirty one of 47 (66%) infants were successfully extubated to NCPAP compared with 18 of 45 (40%) for headbox oxygen. The increase in failure rate in the headbox group was due primarily to increased oxygen requirements in this group. Of the 27 who failed headbox oxygen, 26 were given a trial of NCPAP and 13 did not require endotracheal reintubation. There was no significant difference between the groups in the total number of days of assisted ventilation or the duration of inpatient stay. CONCLUSIONS: NCPAP applied prophylactically after endotracheal extubation reduces the incidence of adverse clinical events that lead to failure of extubation in the seven days after extubation. This reduction is clinically important. The benefits of NCPAP do not seem to be associated with an increased incidence of unwanted side effects.

Female↗
PubMed1997

Use of patient restraints in four Australian teaching hospitals.

To examine the patterns of use of patient restraints in Australian hospitals and the level of adherence to accepted guidelines, we undertook a point-prevalence study in four teaching hospitals in three different States. This involved ward inspections and review of case notes. Overall, 51 (12.5%) of the 408 people audited were being restrained with a variety of physical and chemical agents. The rate of restraint use varied from 8.5% to 18.5% between hospitals. Although the overall prevalence of restraint use increased with age, the hospital with the oldest patients used restraints least. At all hospitals, there was scant documentation in the case notes concerning the use of restraints. The prevalence of restraint use varies widely in different hospitals. As this is not explained by the patient profile, it probably reflects different philosophies of care. Documentation of the use of restraints needs to be improved in all the centres studied.

Adolescent↗
PubMed1996

Oxidative DNA lesions in V79 cells mediated by pentachlorophenol metabolites.

Incubation of the pentachlorophenol (PCP) metabolites, tetrachloro-p-benzoquinone (chloranil, TCpBQ), tetrachloro-p-hydroquinone (TCpHQ) and tetrachloro-p-benzoquinone (TCoBQ) with V79 Chinese hamster cells led to a significant enhancement of the amount of 8-hydroxydeoxyguanosine (8-OH-dG) in DNA. With PCP itself and the metabolite tetrachloro-o-hydroquinone (TCoHQ) no distinct induction of this lesion could be observed. The average yields of 8-OH-dG were about 2-2.5 times above background levels. In addition, TCpBQ and TCpHQ were able to generate DNA single-strand breaks, while PCP, TCoHQ and TCoBQ failed to induce this lesion. All incubations were performed for 1 h without exogenous metabolic activation and concentrations were 25 microM of the respective agent. It is concluded that these metabolites may contribute to the carcinogenicity of PCP observed in mice, by generating reactive oxygen species (ROS) through their redox cycling properties.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Induction of 8-hydroxy-2-deoxyguanosine and single-strand breaks in DNA of V79 cells by tetrachloro-p-hydroquinone.

The biocide pentachlorophenol (PCP) is in part metabolized, by microsomal enzymes, to tetrachloro-p-hydroquinone (TCHQ), which easily oxidizes to its semiquinone radical. Redox cycling of this compound produces reactive oxygen species (ROS) which ultimately may damage cellular DNA. Here, we report on DNA damage generated by TCHQ in hamster lung fibroblasts (V79 cells) using 8-hydroxy-2-deoxyguanosine (8-OH-dG) as a marker of a major oxidative genetic lesion and measuring the induction of DNA single-strand breaks (DNA SSB) with the aid of the alkaline elution assay. TCHQ was administered to cell cultures in concentrations of 6.25, 12.5, 25, and 50 microM for 1 h. 6.25 and 12.5 microM had no significant effect on both parameters, whereas the higher concentrations resulted in increases of the level of 8-OH-dG (2.3- and 2.0-fold, respectively) and induced DNA SSB. The latter lesion may arise from (i) direct attack of OH., (ii) repair of hydroxylated DNA bases, or (iii) cytotoxic effects. Metabolic transformation of PCP to TCHQ and/or other metabolites with quinoid structures and the subsequent generation of ROS, producing oxidative DNA damage, may play a role in PCP-induced carcinogenicity observed in mice.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

The effete in the heat: heat-related hospital presentations during a ten day heat wave.

BACKGROUND: Severe heat-related illness can result in hospitalisation and possibly death. These illnesses are potentially preventable; in Australia high environmental temperatures are common. AIMS: To identify (i) possible risk factors for hospital attendance with heat-related illness during a heat wave, (ii) problems with diagnosis and therapy, (iii) issues in prevention, and (iv) areas for further study. METHODS: A retrospective descriptive survey from four major teaching hospitals in Adelaide, South Australia (SA), was conducted during a ten day period of exceptional heat in February 1993, in order to review all emergency department presentations (i.e. deaths, casualty treatment or hospital admissions) with a heat-related illness as determined by attending doctors' documentation. Demographic, clinical, management and outcome data were collected. RESULTS: Ninety-four patients were classified as having a heat-related illness of whom 78% had heat exhaustion. Eighty-five per cent were age 60 years or over; 20% came from institutional care; 48% lived alone; 30% had poor mobility. Peak presentation followed high daily temperatures for four consecutive days. Severity was related to pre-existing cognitive impairment, diuretic use and presenting temperature, heart rate, blood pressure, plasma sodium and plasma creatinine. Treatment tended to be non-standardised. Mortality was 12%. Seventeen per cent required a more dependent level of residential care upon discharge. CONCLUSION: Problems were identified in accuracy of diagnosis and appropriate intervention. Awareness of the risk factor profile is needed among health workers, to ensure early preventative strategies. Populations to target for future prevention include elderly people (including those in institutional care), patients with cognitive impairment and patients taking diuretics, multiple medication and/or with other severe co-existing illnesses. Treatment could be more standardised.

Adult↗
PubMed1991

A clinical and pathological study of progressive supranuclear palsy.

The clinical features of 26 patients diagnosed as progressive supranuclear palsy are reviewed. The atypical findings were the relatively low frequency of visual complaints (23%) and of significant dementia (20%). As well, the characteristic eye signs, supranuclear ophthalmoplegia of vertical gaze, occurred some years after the onset of the initial symptoms in a small but substantial number (31%), which significantly delayed the diagnosis, in one case by as long as 18 years. The pathological studies on 2 of the clinical cases and an additional 6 cases showed the characteristic pattern of involvement of particular subcortical and brainstem nuclei. In particular, significant degeneration of the pedunculopontine tegmental nucleus was confirmed. Degeneration of the pedunculopontine tegmental nucleus may well play an important role in the motor disability in progressive supranuclear palsy.

Adult↗
PubMed1990

T cell activation in the elderly: evidence for specific deficiencies in T cell/accessory cell interactions.

We studied T cell activation in the healthy aged (greater than 70 years) by examining lymphocyte proliferative responses to various mitogenic stimuli in accessory cell (AC)-dependent and AC-independent systems. Results show that despite a near normal response to the anti-CD3 monoclonal antibody (mAb) OKT3, peripheral blood mononuclear cells (PBM) from the elderly exhibit a profound reduction in phytohaemagglutinin (PHA)-responsiveness (approximately 30% of young adults). This deficit becomes even more severe at suboptimal doses of PHA. Adding exogenous interleukin-2 (IL-2) or pretreating the AC population with gamma interferon (IFN-gamma) returns the level of proliferation to that seen with young adults. Furthermore, replacing "old" AC with AC from young adults or with U937 (a monocytic cell line) in T cell/AC cell-mixing experiments restores PHA-responsiveness in 70% of cases. On the other hand, AC from the aged fully support PHA responses in T cells from young adults. In AC-depleted cultures, purified T cells from the aged respond normally to the co-mitogenic stimuli, PHA + PMA. Taken together, these results suggest that the age-associated diminution in PHA-responsiveness is due, at least in part, to specific deficiencies in T cell/AC communication.

Aged↗
PubMed1989

Faecal incontinence.

Faecal incontinence is a disorder predominantly of the elderly. It is one of the more unpleasant consequences of failing health in old age, both for the sufferer and for the care giver. There are many potential colorectal and anal disorders capable of contributing to or causing faecal incontinence. However, in the elderly, there are two major causes: faecal loading and neurogenic incontinence. Rectal examination is mandatory for all patients with faecal incontinence as it allows the detection of local anorectal abnormalities (not only impaction or faecal loading) which may be responsible for the incontinence. With faecal impaction, there is a history of continuous faecal soiling in the presence of a loaded rectum and in neurogenic incontinence, there is the passage of formed stools with a normal rectal examination. Faecal incontinence imposes a heavy care burden. Often, faecal incontinence can be successfully treated. However, when intractable, continence nurse advisers are available to assist in the selection of suitable pads and underclothing.

Anal Canal↗
PubMedDate not supplied

Discordant results obtained for different methods of HER-2/neu testing in breast cancer--a question of standardization, automation and timing.

BACKGROUND: HER-2/neu positivity is required for the selection of stage IV breast cancer patients for trastuzumab therapy. We compared the results of the recommended immunohistochemistry (IHC) evaluation with the automated ACIS IHC system and with fluorescence in situ hybridization (FISH). These HER-2/neu tissue results were correlated with the serum HER-2/neu (sHER-2/neu) levels at the time of metastatic spread. PATIENTS AND METHODS: A total of 61 IHC slides from 30 patients were stained using the HercepTest. HER-2/neu gene amplification was determined using the Ventana FISH assay. sHER-2/neu levels were measured with the Oncogene Science" ELISA kit. The concordance of HER-2/neu results was determined using the concordance index Kappa (kappa). RESULTS: The best concordance between any IHC and FISH was found for the automated ACIS system (88.5%, kappa=0.68, category "good"). The comparison between the manual interpretations and the automated IHC was categorized as "very good" (95.1%, kappa=0.85). The median sHER-2/neu level of FISH positive patients was significantly higher (67 ng/mL) than that of FISH negative patients (17 ng/mL, p=0.018). The increase in HER-2/neu positivity comparing tissue to stage IV serum was statistically significant (p=0.001). CONCLUSIONS: The concordance between conventional IHC and computerized analysis was very good. The number of patients with stage IV breast cancer with an elevated sHER-2/neu level was much higher than HER-2/neu positivity in tissue. This discrepancy is only partially explained by the influence of tumor load. Patients with an elevated sHER-2/neu level and no tissue overexpression should be considered for retesting of tissue or a new biopsy.

Biomarkers, Tumor↗
PubMedDate not supplied

Plasma levels of HER-2/neu, tumor type M2 pyruvate kinase and its tyrosine-phosphorylated metabolite in advanced breast cancer.

INTRODUCTION: Tyrosine kinase signal transduction pathways are a focus of interest for therapeutic interventions. The oncoprotein HER-2/neu shows tyrosine kinase activity leading to phosphorylation and activation of numerous second-messenger systems. One target of phosphorylation processes is assumed to be the tumor type M2 isoenzyme of pyruvate kinase (TuM2-PK) which has been shown to be elevated in metastatic breast cancer. MATERIALS AND METHODS: We measured the plasma levels of HER-2/neu, TuM2-PK and tyrosine-phosphorylated TuM2-PK (p-TuM2-PK) in 69 patients (pts) with breast cancer and correlated these parameters to each other and to the classical tumor marker CA 27.29. The samples were measured with ELISA assays while CA 27.29 was determined with an automated chemiluminescence assay. For analysis, we formed 5 subgroups according to the plasma HER-2/neu levels (group 1: < 15 ng/ml, n = 28; group 2: 15 < or = x < 50 ng/ml, n = 21; group 3: 50 < or = x < 100 ng/ml, n = 9; group 4: 100 < or = x < 500 ng/ml, n = 7; group 5: > or = 500 ng/ml, n = 4). RESULTS: From the HER-2/neu group 1 to group 5, there was a statistically significant increase of CA 27.29 from 35.8 U/ml to 1095.8 U/ml (p < 0.001). There was also a trend for increasing TuM2-PK levels with increasing HER-2/neu levels (p = 0.126). From the lowest extinction (0.088) to the highest extinction result (2.167) of p-TuM2-PK we found a 25-fold increase, which was reproducible in spiking and dilution experiments proving that TuM2-PK is phosphorylated at tyrosine residues to a certain extent. However, there was no correlation between plasma HER-2/neu and p-TuM2-PK levels. CONCLUSION: TuM2-PK is phosphorylated at tyrosine residues in breast cancer patients. Using the shed antigen of HER-2/neu in plasma as a surrogate marker, we did not find any evidence that this phosphorylation is initiated by the oncoprotein HER-2/neu.

Adult↗