Cerebral blood flow, arteriovenous oxygen difference, and outcome in head injured patients.

Cerebral blood flow (CBF) and other physiological variables were measured repeatedly for up to 10 days after severe head injury in 102 patients, and CBF levels were related to outcome. Twenty five of the patients had a reduced CBF [mean (SD) 0.29 (0.05) ml/g/min]; 47 had a normal CBF, (0.41 (0.10) ml/g/min); and 30 had a raised CBF (0.62 (0.14) ml/g/min). Cerebral arteriovenous oxygen differences were inversely related to CBF and averaged 2.1 (0.7) mumol/ml in the group with reduced CBF, 1.9 (0.5) mumol/ml in the group with normal CBF, and 1.6 (0.4) mumol/ml in the group with raised CBF. Patients with a reduced CBF had a poorer outcome than patients with a normal or raised CBF. Mortality was highest in patients with a reduced CBF, and was 32% at three months after injury, whereas only 21% of the patients with a normal CBF and 20% of the patients with a raised CBF died. There were no differences in the type of injury, initial score on the Glasgow Coma Scale, mean intracranial pressure (ICP), highest ICP, or the amount of medical treatment required to keep the ICP less than 20 mm Hg in each group. Systemic factors did not significantly contribute to the differences in CBF among the three groups. A logistic regression model of the effect of CBF on neurological outcome was developed. When adjusted for variables which were found to be significant confounders, including age, initial Glasgow Coma Score, haemoglobin concentration, cerebral perfusion pressure and cerebral metabolic rate of oxygen, a reduced CBF remained significantly associated with an unfavourable neurological outcome.     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Membrane flow within the myelin sheath in IDPN neuropathy

This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer.     

Closed suction wound drainage and lower-segment caesarean section

Summary. In a randomized controlled study of wound suction drainage after transverse suprapubic incision for lower-segment caesarean section no significant advantages could be demonstrated for routine drainage in terms of wound infection, haematoma formation, duration of hospital stay or analgesic requirements.     

Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard

This retrospective study of formalin-fixed infiltrating breast cancer specimens compared manual immunohistochemical assay with a new image analyzer-assisted immunohistochemical quantitation method, using fluorescence in situ hybridization assay (FISH) as the standard. Following the manual immunohistochemical assay, 189 cases, including most manual immunohistochemically positive and some random negative cases, were analyzed by FISH assay for Her-2/neu gene amplification and by the Automated Cellular Imaging System (ACIS) for immunohistochemical staining. Using the FISH standard, the ACIS immunohistochemical assay attained a higher concordance rate and sensitivity than the manual immunohistochemical assay (91.0% and 88% vs 85.7% and 71%, respectively), with only a slight decrease in specificity (93% vs 96%, respectively). In particular, the ACIS immunohistochemical assay resulted in a higher correlation with the FISH assay in the manual immunohistochemical assay 2+ cases. The ACIS immunohistochemical assay achieved higher accuracy than the manual method according to receiver operating characteristic curve analysis. The ACIS method represents a substantial improvement over the manual method for objective evaluation of the HER-2/neu status.     

Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians. We measured eight highly polymorphic markers spanning this positional candidate gene-rich region in 427 individuals from 55 three-generation pedigrees containing 69 discordant sibling pairs, and calculated multipoint identity by descent (MIBD) probabilities. The results of genetic linkage and association tests indicate that the region between markers D5S2093 and D5S462 is significantly linked to one or more polymorphic genes influencing interindividual variation in systolic blood pressure levels. Since the alpha1B adrenergic receptor and dopamine receptor type 1A genes are located close to these markers, these data suggest that genetic variation in one or both of these G protein-coupled receptors, which participate in the control of vascular tone, plays an important role in influencing interindividual variation in systolic blood pressure levels.      

Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors

Our previous studies showed that glioblastomas express increased urokinase-type plasminogen activator receptors (uPARs) in comparison to low-grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994). To explore whether downregulation of uPAR inhibits tumor formation and invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5¢ end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.     

Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference.

PURPOSE: The purpose of this study was to profile gene expression changes in colorectal tumors to identify new targets and strategies for the management of this disease. EXPERIMENTAL DESIGN: cDNA microarray analysis was used to detect differences in gene expression between normal tissue and colon tumors and polyps isolated from 20 patients. To identify genes that are important in regulating the growth properties of colorectal cancer, RNA interference (RNAi) was used to disrupt expression of several of the overexpressed genes in a colon tumor cell line, HCT116, which showed similar patterns of gene expression as many of the patient tumors. RESULTS: Expression changes of > or =2-fold in approximately one-third of the patients were consistently observed for 2632 of a total of 9592 genes (574 up-regulated genes and 2058 down-regulated genes). Subsequent analysis of 13 genes by quantitative real-time PCR confirmed the reliability of this analysis. RNAi-mediated disruption of the expression of one of these genes, survivin, a potent inhibitor of apoptosis, severely reduced tumor growth both in vitro and in an in vivo xenograft model. CONCLUSIONS: The combined use of microarray analysis and RNAi provides an excellent system to define the role of specific genes that are up-regulated in cancer lead to the increased in vitro and in vivo growth of colon tumors.     

Outcome of children with respiratory symptoms without objective evidence of asthma: a two-year, prospective, follow-up study

This study evaluated the outcome of 33 children with asthma-like symptoms without objective evidence of asthma, and the role of certain factors in predicting the development of clinical asthma in these children. Data on symptom histories, lung functions (flow-volume spirometry, free running test and methacholine inhalation challenge test) and atopic sensitization (skin prick tests and markers of eosinophilic inflammation) were collected twice with an interval of 2 y, and the diagnoses were re-evaluated after the follow-up period. Based on the results, it was concluded that one-third of the children with prolonged or recurrent lower airway symptoms, such as cough or wheeze, either have mild asthma or will develop asthma in the near future. Children who had a significant response [≥ 10% fall in forced expiratory volume in 1 s (FEV1)] in the free running test formed a risk group for active asthma, whereas other baseline characteristics seemed not to predict the outcome.     

Randomized trial examining cerebral haemodynamics following artificial or animal surfactant

To determine the effects of animal and artificial surfactants on cerebral haemodynamics, 20 premature babies receiving mechanical ventilation were randomized to receive Curosurf or Exosurf surfactant. Anterior cerebral artery blood flow velocity (CABFV) was measured using Doppler ultrasound before and up to 2 h after treatment. Following animal surfactant there was a rapid reduction in CABFV (median -36%, range -43% to +8%, p < 0:01), whereas artificial surfactant resulted in a slower rise which was less marked (median +20%, range -7% to +62%, p < 0:05). There were no significant changes in blood pressure. Two hours after administration, the oxygenation index (OI) improved significantly only in babies receiving animal surfactant. In this group there was a significant association between the change in CABFV at 1 min and the change in OI at 2 h ( r = 0:66, p < 0:05). Animal surfactant produces rapid improvements in ventilation which are associated with marked alterations in cerebral haemodynamics.