Incidence of central line related/associated bloodstream infections in an acute hospital.

Bloodstream infection related to a central venous catheter in the intensive care unit is a substantial clinical and economic problem. The aim of the study was to examine the incidence of central line related bloodstream infections and central line associated bloodstream infections in Our Lady of Lourdes Hospital, Drogheda, during a six month period, using an active patient based prospective surveillance method. CLRBSI rate in ICU/HDU was 0.93/1000 central line days. There was no CLABSI identified in the studied time period. However, further interventions are needed, particularly with CVC care bundle. Also, the implementation of 2% chlorhexidin in 70% isopropylalcohol use for skin asepsis, which is recommended by the Irish national guidelines, would be beneficial.

All radial scars/complex sclerosing lesions seen on breast screening mammograms should be excised.

AIM: To determine the incidence of pre-malignant and malignant conditions in radial scars identified from screening mammograms in women taking part in the UK NHS breast cancer screening programme. METHODS: All women in our screening population from 1988 to 2002 with a radiological diagnosis of radial scar or complex sclerosing lesion confirmed on subsequent histopathology were included in this study. Patients were investigated with fine needle aspiration cytology then localisation biopsy (n=46) or straight to localisation biopsy (n=78). Patients where divided into two groups, one with pure RS/CSL with no associated epithelial features and the second with associated ADH, DCIS or invasive cancer. RESULTS: One hundred and twenty-four lesions were confirmed histologically as radial scar or complex sclerosing lesions. The median age was 58 years. Of the 124 patients, 82 were pure RS/CSL. Forty-two had associated epithelial lesions, 22 patients had ADH and 20 patients had either in situ or invasive carcinoma. Where FNA was performed (n=46), mammograms had shown three lesions suspicious of cancer, which were not proven histologically. Mammograms picked up five malignancies out of the nine RS/CSL with associated cancers. Of these, FNA confirmed malignancy in only two patients. Where FNA was not done (n=78), mammogram had read five pure RS/CSL as cancers. It picked up only four cancers in RS lesions with DCIS/Ca out of 11. CONCLUSION: All screen-detected stellate lesions should be excised due to their association with pre-malignant and malignant conditions.

Alveolar and plasma concentrations of interleukin-8 and vascular endothelial growth factor following oesophagectomy.

The acute respiratory distress syndrome occurs in approximately 10% of all patients undergoing elective oesophagectomy. Local increases in lung pro-inflammatory cytokines have been previously detected in high-risk patients before the development of the acute respiratory distress syndrome. We hypothesised that similar changes would occur following oesophagectomy. Two groups of patients were studied. In the collapsed lung group (n = 11), interelukin-8 and vascular endothelial growth factor were measured in bronchoalveolar lavage samples obtained from the intra-operative collapsed lung after operation. In the ventilated lung group (n = 10), bronchoalveolar lavage was performed after operation from the ventilated lung and cytokines measured. Cytokines were also measured in peripheral blood samples before and after operation. Bronchoalveolar lavage cytokine levels in both lungs were of an order of magnitude greater than in peripheral blood. Pulmonary pro-inflammatory cytokine release occurs following oesophageal surgery and may indicate subclinical lung injury.

Neuronal nitric oxide synthase mediates halothane-induced cerebral microvascular dilation.

BACKGROUND: The causes of volatile anesthetic-induced cerebral vasodilation include direct effects on smooth muscle and indirect effects via changes in metabolic rate and release of mediators from vascular endothelium and brain parenchyma. The role of nitric oxide and the relative importance of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) are unclear. METHODS: Rat brain slices were superfused with oxygenated artificial cerebrospinal fluid. Hippocampal arteriolar diameters were measured using computerized videomicrometry. Vessels were preconstricted with prostaglandin F2alpha (PGF2alpha; halothane group) or pretreated with 7-nitroindazole sodium (7-NINA, specific nNOS inhibitor, 7-NINA + halothane group) or N-nitro-L-arginine methylester (L-NAME; nonselective NOS inhibitor, L-NAME + halothane group) and subsequently given PGF2alpha to achieve the same total preconstriction as in the halothane group. Increasing concentrations of halothane were administered and vasodilation was calculated as a percentage of preconstriction. RESULTS: Halothane caused significant, dose-dependent dilation of hippocampal microvessels (halothane group). Inhibition of nNOS by 7-NINA or nNOS + eNOS by L-NAME similarly attenuated halothane-induced dilation at 0.6, 1.6, and 2.6% halothane. The dilation (mean +/- SEM) at 1.6% halothane was 104 +/- 10%, 65 +/- 6%, and 51 +/- 9% in the halothane, 7-NINA + halothane and L-NAME + halothane groups, respectively. The specificity of 7-NINA was confirmed by showing that acetylcholine-induced dilation was not inhibited by 7-NINA but was converted to constriction by L-NAME. CONCLUSIONS: At clinically relevant concentrations, halothane potently dilates intracerebral arterioles. This dilation is mediated, in part, by neuronally derived nitric oxide. Endothelial NOS does not play a major role in halothane-induced dilation of hippocampal microvessels.

Dexmedetomidine modulates cardiovascular responses to stimulation of central nervous system pressor sites.

UNLABELLED: Halothane attenuates the alterations in arterial pressure (BP) and heart rate (HR) produced by central nervous svstem (CNS) stimulation. We examined the effects of the alpha2-adrenergic agonist dexmedetomidine, with and without halothane, on cardiovascular regulation during CNS pressor site stimulation in chronically instrumented cats. Stimuli trains via bipolar stimulating electrodes in the hypothalamus and reticular formation elicited pressor responses. Dexmedetomidine-induced (15 microg/kg PO) bradycardia was greater in the presence of halothane. CNS stimulation increased BP and HR, which were dose-dependently attenuated by halothane (hypothalamic stimulation 71 +/- 9 mm Hg at control, 25 +/- 5 and 15 +/- 3 mm Hg at 1.0% and 1.5% halothane, respectively). Although dexmedetomidine alone did not alter pressor responses, halothane plus dexmedetomidine attenuated pressor responses in a potentially synergistic fashion (hypothalamic stimulation 67 +/- 8 mm Hg at control, 2 +/- 1 and 1 +/- 0.4 mm Hg at 1.0% and 1.5% halothane, respectively). These results suggest differences in the disruptive effects of CNS-mediated cardiovascular responses by halothane and dexmedetomidine, and that dexmedetomidine has an anesthetic-sparing effect on these CNS-mediated cardiovascular control mechanisms, potentiating the depressant effect of halothane. IMPLICATIONS: A new potential anesthetic adjunct, dexmedetomidine, does not attenuate brain-mediated increases in blood pressure, but the combination of dexmedetomidine and the anesthetic halothane acts to modulate central cardiovascular responses.

Pretreatment with dexmedetomidine: altered indices of anesthetic depth for halothane in the neuraxis of cats.

UNLABELLED: The sedative and anesthetic-sparing ability of the alpha2-adrenergic agonist dexmedetomidine is well documented. In this study, we identified the effects of halothane, with and without dexmedetomidine, on hemodynamic and electroencephalographic (EEG) variables and quantified the concentration of halothane resulting in various anesthetic depth indices mediated through the central nervous system (CNS) in chronically instrumented cats. Halothane was given alone or after dexmedetomidine (15 microg/kg p.o.). In both groups, four indices of anesthetic depth--minimum alveolar anesthetic concentration (MAC; no movement to noxious stimuli), MAC(BAR) (no autonomic response to noxious stimuli), MAC(BS) (EEG burst suppression), and MAC(ISOELECTRIC) (EEG isoelectricity)--were determined. Halothane decreased arterial blood pressure, heart rate, and higher frequency components of the EEG before the onset of burst suppression and isoelectricity. Dexmedetomidine pretreatment augmented the actions of halothane on arterial pressure, heart rate, and the EEG. Dexmedetomidine reduced the halothane concentrations resulting in MAC (from 1.22% +/- 0.06% to 0.89% +/- 0.08%) and MAC(BAR) (from 1.81% +/- 0.05% to 1.1% +/- 0.10%), but not those resulting in MAC(BS) (3.01% +/- 0.17% vs 3.14% +/- 0.10%) or MAC(ISOELECTRIC) (4.39% +/- 0.26% vs 4.65% +/- 0.12%). These results suggest that dexmedetomidine does not alter various CNS-mediated indices of anesthetic action to equivalent degrees and that there are dissimilar degrees of an anesthetic-sparing action at different levels of the neuraxis. IMPLICATIONS: The anesthetic adjuvant dexmedetomidine seems to differentially alter central nervous system-mediated indices of anesthetic action. Lower brainstem or spinal determinants of anesthetic depth (movement and hemodynamic responses) are more attenuated than those of higher brain functions, such as the electroencephalogram.

Apoptosis: basic concepts and potential significance in human cancer.

Numerous factors trigger or repress apoptosis (genetically mediated individual cell death). The details of signal transduction pathways and regulation of apoptosis by numerous oncogene and tumor suppressor gene products are not fully understood. Bcl-2 inhibits apoptosis induction by a variety of stimuli. Caspases are the basic effectors of apoptosis, leading ultimately to fragmentation of DNA, at which stage apoptosis can be identified. Apoptosis affects scattered individual cells that have extremely dense nodular, beaded, or crescentic chromatin, and differs morphologically, biochemically, and topographically from necrosis. Apoptosis is a negative growth-regulating mechanism in cancer, and its extent varies with tumor type. Apoptosis reflects tumor cell kinetics; aggressive tumors often show conspicuous apoptosis, and there are significant linear correlations between apoptotic and mitotic indices in many tumor types. The relative importance of p53, c-Myc, Rb, and the Bcl-2 homologs in the regulation of apoptosis in different human cancers is not clear. Further pathologic investigations on apoptosis in human cancer are needed to reaffirm recent experimental findings and to explain more fully the regulation and biological significance of apoptosis in vivo.

The effects of graded hypoxia on intraparenchymal arterioles in rat brain slices.

Hypoxia-induced changes in intracerebral arterioles, the major determinants of local cerebral oxygen delivery, are not well understood. Hippocampal arteriolar diameters were measured in rat brain slices using computerized videomicroscopy. In group 1 (control), artificial cerebrospinal fluid oxygen tension (PO2) was maintained at 500 mmHg. In groups 2 and 3, PO2 was gradually reduced to anoxia (95% N2/5% CO2). In group 3, prostaglandin F2a alpha was given to approximate physiological myogenic tone. PCO2 and pH were controlled. Graded hypoxia progressively dilated vessels (PO2 300 mmHg = 2.4 +/- 1.2%, 4.2 +/- 1.6%; PO2 90 mmHg = 15.4 +/- 3.0%, 14.5 +/- 1.8%; groups 2 and 3, respectively). The presence of preconstriction did not influence the extent of hypoxia-induced dilation. This vasorelaxation may be important in maintaining cerebral oxygen delivery during microvascular hypoxia.

Apoptosis occurs independently of bcl-2 and p53 over-expression in non-small cell lung carcinoma.

Certain oncogenes and tumour suppressor genes are known to modulate apoptosis. To investigate whether overexpressed bcl-2 and abnormally stabilized p53 are associated with reduced apoptosis in paraffin sections of non-small cell lung carcinoma, apoptotic, mitotic, and Ki-67 labelling indices were determined and correlated with bcl-2 and p53 immunoreactivity in 54 squamous cell carcinomas and 22 adenocarcinomas. Nineteen squamous cell carcinomas (35.2%) showed over-expression of bcl-2, but all 22 adenocarcinomas were bcl-2 negative. Thirty-seven squamous cell carcinomas (68.5%) and 13 adenocarcinomas (59.1%) showed p53 over-expression. Apoptotic tumour cells were identified among p53 positive and bcl-2 positive tumour cells. There was a significant linear correlation between apoptotic indices and mitotic indices. bcl-2 over-expression and p53 over-expression were not associated with attenuated apoptosis, or altered mitotic or Ki-67 labelling indices in either tumour type. Neither bcl-2 nor p53 was of prognostic significance. These results suggest that apoptosis in non-small cell lung carcinoma occurs independently, and is not modulated primarily by, bcl-2 or p53. It is likely that the effects on apoptosis of bcl-2 and p53 are countered by those of other oncogene products and/or additional factors that regulate apoptosis in vivo.

Colocalisation of human immunodeficiency virus and human cytomegalovirus infection in brain autopsy tissue from AIDS patients.

We have examined 26 human AIDS brains obtained at post mortem for infection by human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV), and for dual infection of cells by both viruses. The techniques used were enzyme-linked immunocytochemistry for HCMV and in situ hybridisation using a cDNA probe for HIV. Using these techniques, HCMV infection was detected in 14 brains, HIV infection in 14 brains, and coinfection with HIV and HCMV in 7 brains. Four case of dual HIV/HCMV infection were found where no colocalisation could be detected. In randomly chosen dually infected areas 19.2% of infected cells were coinfected with both viruses. Although cells identified morphologically as macrophages were the most common infected cell type, astrocytes and neurons were both singly and doubly infected with HIV and HCMV. Complete clinical data were available for 4 of the 7 cases with coinfection and each had AIDS dementia complex.

In situ end-labelling, light microscopic assessment and ultrastructure of apoptosis in lung carcinoma.

AIMS: To compare in situ end-labelling (ISEL) of apoptosis in lung carcinoma with quantitative and semiquantitative light microscopic assessment and ultrastructural observations. METHODS: ISEL of apoptosis was evaluated in 42 lung carcinomas (24 squamous cell carcinomas, 12 adenocarcinomas and six small cell carcinomas). Results were correlated semiquantitatively with the extent of apoptosis in haematoxylin and eosin stained sections, with apoptotic indices and with ultrastructural observations (nine cases). RESULTS: In each tumour type the extent of apoptosis identified by ISEL correlated with that observed on light and electron microscopy. Tumour cells undergoing apoptosis showed either uniform nuclear staining with a surrounding "halo" or peripheral nuclear membrane staining. The latter pattern was more prominent in small cell carcinoma and correlated ultrastructurally with early apoptosis. A variable proportion of apoptotic cells and apoptotic bodies were unlabelled. Necrotic tumour cells were weakly stained but were distinguishable from apoptotic cells. CONCLUSIONS: ISEL, if used in conjunction with standard methods for investigating apoptosis, is a useful adjunct to the investigation of apoptosis in human tumour tissue.

Tumor type is a determinant of susceptibility to apoptosis.

Little quantitative data exist on the extent of apoptosis (genetically-mediated cell deletion) in different human tumor types. Hematoxylin and eosin-stained paraffin sections of 102 malignant tumors (58 types) were evaluated for apoptotic cells and apoptotic bodies, using the 40x objective with a calibrated eye-piece and avoiding necrotic zones. The percentage of apoptotic cells and apoptotic bodies in the total number of tumor cells examined was designated as the apoptotic index (AI) for each case. There was a wide range in the AI for different tumor types: 45 tumors had AI < 1% and 93 had an AI of < 7%. In 107 additional tumors (11 types), the AI was determined to be within the same low, intermediate, or high range as the index cases. Apoptotic nuclear material was usually more prominent than mitoses. These results suggest that each tumor type has a characteristic AI that reflects innate tumor cell susceptibility to undergo apoptosis. Additional data are needed to determine whether significant variations in AI correlate with altered proliferative indices, aberrant oncogene/tumor suppressor gene expression, and standard clinicopathologic variables.

Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival.

Contemporary management of patients with follicular pattern thyroid cancer remains uncertain. This retrospective multivariate analysis studied 410 such patients treated in a cancer hospital in the years 1932-72 and providing a follow-up of 20 years. In papillary carcinoma thyroxine administration (P < 0.005) and surgery (P < 0.001) improved survival together with youth (P < 0.001) and being female (P < 0.05). In follicular carcinoma, thyroxine therapy (P < 0.001) increased survival as did surgery but it failed to reach significance (P = 0.19); increasing age (P < 0.001), stage M1 (P < 0.05) and 'complete' radiotherapy (P < 0.05) decreased survival. In anaplastic carcinoma survival was improved by thyroxine therapy (P < 0.001), a new finding, but decreased by stages T3 (P < 0.001) and M1 (P < 0.05); however, radiotherapy, the mainstay in control of local disease, did not increase survival. Overall, total thyroidectomy reduced local recurrence with an increase in complications and no operation gained a significant increase in survival. Radio-iodine achieved no benefit in survival which raises the possibility of confounding. Thyroxine therapy is indicated as initial treatment of follicular cell thyroid cancer.

Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings.

Schizophrenia may result from the concerted action of several pathophysiological factors. This pilot study compared the distribution of measurements of three such putative factors in 11 schizophrenics and their siblings: a neurophysiological deficit in auditory sensory gating, diminished hippocampal volume, and increased catecholamine metabolism. Abnormal auditory sensory gating was found in all schizophrenics in the 11 families studied and in 8 of their 20 siblings. Compared with the schizophrenics, the clinically unaffected siblings with abnormal auditory gating had larger hippocampal volume. There was no similar difference for the siblings with normal gating. The siblings with abnormal auditory gating also had lower homovanillic acid levels than the other siblings. The data suggest that a familial neuronal deficit, identified by diminished sensory gating, may be a necessary, but not sufficient factor in the pathogenesis of schizophrenia. Individuals with this deficit are generally clinically unaffected, except for schizophrenics, who also have other abnormalities, such as diminished hippocampal volume and increased catecholamine metabolism.

A 25-year prospective study of modified radical mastectomy (Patey) in 193 patients.

The results of a prospective study over 20 years of 193 patients with breast carcinoma treated by Patey mastectomy are presented together with details of the operative technique employed. One hundred and twenty-eight cases (66%) were stage 1 (T1/T2 N0), 46 (24%) were stage 2 (T1/T2 N1), 18 (9%) were stage 3 (T3 N0/N1), and one was stage 4 (M1). The probability of survival together with 95% confidence intervals for stage 1 (T1/T2 N0) at 10 years was 79% (71-88); and at 15 years 74% (61-87). For stage 2 (T1/T2 N1), the probability of survival at 10 years was 64% (48-79), and at 15 years 60% (44-76). For stage 3 (T3 N0/N1), the probability of survival at 10 years was 70% (45-95) and nobody survived at 15 years. These differences between the clinical stages lacked significance [Log-rank test: chi 2 = 3.44 df = 2 P = 0.18]. There were nine patients (5%) who developed local recurrence without systemic metastases. There was no postoperative mortality, and morbidity was low. Axillary node metastases depressed survival with probability of survival at 10 years 43% (29-57) in contrast to those without it 90% (84-96) [log-rank test: chi 2 = 39.42 df = 1 P < 0.0001]. Patey mastectomy should be considered for patients with T1 or T2 tumours who choose mastectomy rather than breast conservation. It is an effective local treatment which is of particular relevance in countries where radiotherapy is not available.