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Biomedical subjects

D W Green

Publications and source records attributed to D W Green.

At least 19 recordsLinked to original sources

A retrospective study of changes in cerebral oxygenation using a cerebral oximeter in older patients undergoing prolonged major abdominal surgery.

BACKGROUND AND OBJECTIVE: The objective was to carry out a retrospective study of changes in regional cerebral oxygen saturation (rSO2) using the Somanetics Invos Cerebral Oximeter (SICO) in older patients undergoing prolonged major abdominal surgery. Since evidence is accumulating that detection and correction of falls in rSO2 may be associated with a reduced incidence of postoperative cognitive dysfunction, the study assessed the incidence and possible predisposing factors for significant falls in rSO2 and strategies for correction. METHODS: Data from 46 consecutive patients aged 55 yr or above undergoing major abdominal surgery were collected and studied. A SICO electrode was placed over the right forehead prior to commencement of anaesthesia and values of rSO2 were recorded automatically on a floppy disk at 20 s intervals throughout the procedure and until transfer of the patient to the postanaesthesia care unit. Anaesthesia and physiological data were routinely collected by the author on an anaesthetic record computer and transferred to an Excel spreadsheet for analysis. RESULTS: Average duration of the surgery exceeded 7 h. Average blood loss was 1363 mL (interquartile range 500-2000). In 11 of the 46 patients the rSO2 drop exceeded 20%, and in six, there was a significant temporal association of rSO2 drop with ongoing major haemorrhage. In 23 of the 46 patients, a maximum drop in rSO2 occurred, which was about 15% or more. Fall in rSO2 in the 46 patients significantly correlated with blood loss (P < 0.05) and percentage fall in haemoglobin (Hb) (P = 0.01) but not with lowest Hb. Despite maintenance of conventional haemodynamic parameters such as systolic blood pressure (BP) in most patients, the fall in rSO2 seemed only reversible by blood transfusion. In five of the six patients who experienced the greatest decline in rSO2 during haemorrhage, there was no correlation between fall in rSO2 and systolic BP. CONCLUSIONS: This retrospective study confirms that a significant reduction in rSO2 is a common accompaniment to prolonged major abdominal surgery in elderly patients, especially if associated with blood loss, and is correctable by blood transfusion. In most cases, these changes would have gone unnoticed with conventional monitoring.

Abdomen↗

Language control in the bilingual brain.

How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.

Adult↗

Invos Cerebral Oximeter compared with the transcranial Doppler for monitoring adequacy of cerebral perfusion in patients undergoing carotid endarterectomy.

AIM: The aim of this prospective study was to assess the correlation between signals obtained during carotid endarterectomy (CEA) under local (LA) or general anesthesia from the Somanetics Invos cerebral oximeter (CO) and transcranial Doppler (TCD). METHODS: Forty patients were enrolled in the study. The percentages fall in TCD mean flow velocity (FVm) and CO regional oxygen saturation (rSO2) on the ipsilateral side following clamping were recorded and the correlation coefficient and Spearman's coefficient of rank correlation were calculated. RESULTS: Fourteen patients were not included in the statistical analysis because either no TCD window or reliable TCD signal was obtained. The remaining 26 patients had a fall in either FVm, rSO2 or both during carotid clamping. There was a highly statistically significant correlation between the percentage fall in FVm and rSO2 with a correlation coefficient of 0.73, P<0.0001, with a 95% confidence interval (CI) for r=0.48 to 0.87; Spearman's coefficient of rank correlation (rho) =0.67, P=0.0008, with a 95% CI for rho=0.384 to 0.84. A significant decline in both TCD and rSO2 was noted in 3 patients under LA out of which 2 required shunts for alteration in conscious level. In 2 LA patients there was a significant decline in TCD but not in rSO2 and the endarterectomy was completed without a shunt. CONCLUSIONS: Regional oxygen saturation correlates well with FVm during carotid clamping. However, the inability to obtain reliable TCD FVm readings in 35% of patients is a serious disadvantage for this monitor. It appears that CO is a satisfactory and possibly superior device for monitoring adequacy of cerebral perfusion and oxygenation during CEA in comparison with the TCD.

Aged↗

The treatment of large (>70 degrees) thoracic idiopathic scoliosis curves with posterior instrumentation and arthrodesis: when is anterior release indicated?

STUDY DESIGN: Retrospective clinical study from 2 centers. OBJECTIVE: To analyze the efficacy of posterior instrumentation and arthrodesis for thoracic idiopathic scoliosis curves more than 70 degrees. SUMMARY OF BACKGROUND INFORMATION: The increasing use of thoracoscopic techniques in deformity surgery has led several investigators to advocate anterior release followed by posterior instrumentation when treating "stiff" thoracic curves 60 degrees-70 degrees. To our knowledge, no study has been published to define indications for anterior surgery in thoracic idiopathic scoliosis. METHODS: This is a retrospective review of patients 20 years and younger, with idiopathic scoliosis and thoracic curves more than 70 degrees treated with isolated posterior instrumentation and arthrodesis at 2 institutions from 1989 to 1999. A total of 50 patients were identified, and 46 were available for minimum 2-year radiographic follow-up. Of the 50 patients, 44 had bend films taken before surgery. All patients were treated with third-generation segmental spinal instrumentation using a varied combination of hooks, wires, and screws. RESULTS: Average patient age at surgery was 14.4 years (range 10-20), and average radiographic follow-up was 4.4 years (range 2-11.5). Average preoperative thoracic curve was 75 degrees (range 70 degrees-88 degrees), and average bend was 47 degrees (range 28 degrees-60 degrees), a flexibility of 37%. Average postoperative curve was 25 degrees (range 10 degrees-46 degrees), and it was 27 degrees (range 11 degrees-46 degrees) at latest follow-up, a correction of 64%. The average length of surgery was 6.15 hours, mean hospital stay was 8 days, and average blood loss was 1100 cc. The Scoliosis Research Society 22 or 24 was available at a minimum of 2 years in 46 of 50 patients. Mean domain scores were: pain 4.4, self-image 4.3, function 4.3, mental health 4.3, satisfaction 4.7, and total 4.4. Complications included 1 pseudarthrosis, 1 implant removal for prominence, and 1 implant removal for late operative site pain. CONCLUSION: Using posterior surgery only, we have been able to at least equal the results reported in the literature by investigators using combined approaches. Isolated posterior instrumentation and arthrodesis achieve satisfactory cosmetic, radiographic, and patient-based outcomes in adolescents with idiopathic scoliosis with thoracic curves 70 degrees-90 degrees, without the added expense and morbidity of anterior release.

Adolescent↗

Novel osteoinductive biomimetic scaffolds stimulate human osteoprogenitor activity--implications for skeletal repair.

The development of new bone formation strategies offers tremendous therapeutic implications in a variety of musculoskeletal diseases. One approach involves harnessing the regenerative capacity of osteoprogenitor bone cells in combination with biomimetic scaffolds generated from appropriate scaffold matrices and osteoinductive factors. The aims of our study were to test the efficacy of two innovative osteoinductive agents: the osteoblast stimulating factor-1 (osf-1), an extracellular matrix-associated protein, and osteoinductive extracts of Saos-2 cells on human osteoprogenitor cells. Saos-2 extracted osteoinductive factors significantly stimulated alkaline phosphatase specific activity in basal and osteogenic conditions. Osf-1 significantly stimulated chemotaxis, total colony formation, alkaline phosphatase-positive colony formation, and alkaline phosphatase specific activity at concentrations as low as 10 pg/ml compared with control cultures. Osteoinductive factors present in Saos-2 cell extracts and osf-1 promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on 3-D scaffolds. The successful generation of 3-D biomimetic structures incorporating osf-1 or osteoinductive factors from Saos-2 cells indicates their potential for de novo bone formation that exploits cell-matrix interactions.

Aged↗

The choice of inhalation anaesthetic for major abdominal surgery in children with liver disease.

Many children with liver disease undergo major abdominal surgery. Maintenance of anaesthesia is thus an important consideration in this surgical population. Despite a comprehensive and painstaking review of the literature, a sound evidence base, on which a choice of inhalation anaesthetic may be made, is lacking due to limited research in these patients. Differences between the more recent agents such as isoflurane, sevoflurane and desflurane are minor. Sevoflurane is favoured in paediatric practice for gaseous induction, but desflurane or isoflurane are marginally the preferred agents for maintenance of anaesthesia in children with liver disease undergoing major abdominal surgery. However, on the evidence that exists, much of it admittedly in animals and in adults, all three are preferable to halothane in this group of patients. More work is needed in this area before sound conclusions can be drawn and one agent proved to be definitely superior to the others.

Abdomen↗

Suppression of beta-catenin inhibits the neoplastic growth of APC-mutant colon cancer cells.

Mutations involving the adenomatous polyposis coli (APC) tumor suppressorgene/beta-catenin signaling pathway have been identified in the majority of colon carcinomas. However, the role of aberrant beta-catenin signaling in the neoplastic growth of APC-mutant colon cancer cells has not been directly studied. To address this question, antisense oligonucleotides have been used to specifically down-regulate beta-catenin expression in APC-mutant human colon carcinoma cells. Antisense-mediated suppression of beta-catenin inhibits the in vitro proliferation, anchorage-independent growth, and cellular invasiveness of APC-mutant human colon carcinoma cells. The systemic administration of beta-catenin antisense oligonucleotides down-regulates beta-catenin expression in vivo in human colon cancer xenografts in nude mice. Such treatment inhibits the tumorigenic growth of colon cancer xenografts and can completely eradicate tumors in some treated animals. These studies formally demonstrate the critical role of beta-catenin signaling in the neoplastic growth of APC-mutant colon cancer cells and suggest that strategies targeting beta-catenin may be of use in the therapy of colon cancer.

Animals↗

Beta-catenin antisense treatment decreases beta-catenin expression and tumor growth rate in colon carcinoma xenografts.

BACKGROUND: Loss of the adenomatous polyposis coli (APC) tumor suppressor gene plays a significant role in colorectal carcinogenesis. One function of the APC gene product is to regulate beta-catenin, a protein that plays a role in cell adhesion and also regulates the activity of certain transcription factors. To more precisely delineate the role of beta-catenin signaling in colon cancer growth, we treated mice bearing APC-mutant SW480 colon cancer xenografts with antisense oligonucleotides (ODNs) directed against beta-catenin mRNA and examined effects on beta-catenin expression and tumor growth. METHODS: Balb/C nude mice underwent subcutaneous injection of 1 x 10(6) SW480 cells to establish tumor xenografts. In one experiment, tumors were allowed to grow for 7 days, after which time animals were randomized to undergo daily intraperitoneal injections of either antisense beta-catenin ODN at doses of 5, 10, or 20 mg/kg, scrambled sequence beta-catenin ODN control, or saline control for 7 days. Tumors were excised and homogenized, and tumor lysates subjected to gel electrophoresis and Western blotting for beta-catenin protein quantification. In a second experiment, tumor-bearing animals began receiving daily intraperitoneal injections of either antisense beta-catenin ODN at doses of 5, 10, or 20 mg/kg, scrambled sequence beta-catenin ODN control, or saline control. Tumor growth was quantitated by measuring tumor volumes twice weekly. A third experiment evaluated the antitumor effects of daily bolus dosing versus continuous infusion of beta-catenin antisense ODNs (20 mg/kg). RESULTS: Treatment of APC-mutant colorectal carcinoma xenografts with beta-catenin antisense resulted in a dose-dependent down-regulation in beta-catenin protein expression as shown by Western blotting. Treatment of tumor-bearing mice with antisense directed at beta-catenin also demonstrated a dose-dependent inhibition of tumor growth. There appears to be little difference in the antitumor effects of antisense ODNs administered by continuous infusion or bolus dosing schedules. CONCLUSIONS: beta-Catenin expression plays a critical role in the tumorigenic growth of APC-mutant colon cancer xenografts. Strategies targeting beta-catenin, including the use of antisense ODNs, may be of use in the treatment of human colon cancer.

Animals↗

Contingency, causation, and adaptive inference.

In contingency judgment tasks involving 2 event types, individuals weight the a and b cells of a 2 x 2 contingency table more than the c and d cells. Some theorists have argued that they can provide normative justifications for this weighting and that the weighting reflects simple heuristics that are adaptive in the real world. The authors show that, to avoid error, individual judgments about real contingencies should be more subtle than these supposedly adaptive heuristics allow.

Bayes Theorem↗

Understanding microworlds.

Little is known about how individuals understand change in complex systems. In the natural world, for instance, the effects of change need to be understood in terms of two-way (interdependent) causal processes. Based on subject's ratings of the causal likelihood that a given change will yield a target effect and on subjects' ratings of the impact of a given change on specified populations in a microworld, White (1997, 2000) argued that individuals in fact understand change in terms of one-way causal processes and assume that causal effects decline with distance from the source of the change. An alternative view is that the ratings reflect individuals' mental simulations of change as elicited by the tasks. Experiments 1 and 2 confirm that such ratings are task dependent and that individuals make no general assumption that causal effects decrease with distance. Experiment 3 shows that when required to explain a pattern of change in the size of a population individuals can construct two-way causal explanations consistent with this mental simulation proposal.

Adolescent↗

Medical complications in scoliosis surgery.

Several medical complications can occur after scoliosis surgery in children and adolescents. They include the syndrome of inappropriate antidiuretic hormone; pancreatitis; cholelithiasis; superior mesenteric artery syndrome; ileus; pnemothorax; hemothorax; chylothorax; and fat embolism. This review focuses on the pathophysiology, diagnosis, and treatment of the various conditions that occur after correction of spinal deformity. Attention is given to recent literature specifically related to scoliosis surgery. Surgical complications like urinary tract infection, wound infection, and hardware failure will not be addressed.

Adolescent↗

HER2/neu antisense targeting of human breast carcinoma.

Overexpression of the HER2/neu oncogene is observed in approximately 30% of human breast carcinoma specimens. HER2/neu overexpression is a negative prognostic factor in breast cancer patients. Cancer cells that overexpress HER2/neu may also be less sensitive to chemotherapy. In order to further define mechanisms by which HER2/neu overexpression drives neoplastic cell growth and chemoresistance, antisense oligonucleotides (ODNs) have been utilized to selectively down-regulate HER2/neu expression in human breast cancer cells. Such antisense ODNs suppress HER2/neu mRNA and protein levels in a dose-dependent, sequence-specific manner. Down-regulation of HER2/neu expression in HER2/neu overexpressing breast cancer cells inhibits cell cycle progression in G0/G1 and results in apoptotic cell death. In tissue culture studies, combined treatment of HER2/ neu overexpressing breast cancer cells with HER2/neu antisense ODNs and conventional chemotherapeutic agents results in synergistic inhibition of cancer cell growth and activation of apoptotic cell death mechanisms. These studies have been extended to demonstrate synergistic antitumor effects following systemic treatment with antisense ODNs plus doxorubicin in nude mice bearing human breast carcinoma xenografts. Collectively these findings demonstrate that HER2/neu overexpression stimulates anti-apoptotic cell survival mechanisms and suggest that HER2/neu antisense ODNs may be of use in cancer therapeutics.

Animals↗

The IF(1) inhibitor protein of the mitochondrial F(1)F(0)-ATPase.

Recent studies on the IF(1) inhibitor protein of the mitochondrial F(1)F(0)-ATPase from molecular biochemistry to possible pathophysiological roles are reviewed. The apparent mechanism of IF(1) inhibition of F(1)F(0)-ATPase activity and the biophysical conditions that influence IF(1) activity are summarized. The amino acid sequences of human, bovine, rat and murine IF(1) are compared and domains and residues implicated in IF(1) function examined. Defining the minimal inhibitory sequence of IF(1) and the role of conserved histidines and conformational changes using peptides or recombinant IF(1) is reviewed. Luft's disease, a mitochondrial myopathy where IF(1) is absent, is described with respect to IF(1) relevance to mitochondrial bioenergetics and clinical observations. The possible pathophysiological role of IF(1) in conserving ATP under conditions where cells experience oxygen deprivation (tumor growth, myocardial ischemia) is evaluated. Finally, studies attempting to correlate IF(1) activity to ATP conservation in myocardial ischemic preconditioning are compared.

Adenosine Triphosphate↗

Nucleated red blood cells in healthy infants of women with gestational diabetes.

OBJECTIVE: To evaluate whether absolute nucleated red blood cell (RBC) counts are elevated in large-for-gestational-age (LGA) infants of women with gestational diabetes compared with appropriate-for-gestational-age (AGA) infants of women with or without gestational diabetes. METHODS: We compared absolute nucleated RBC counts during the first 12 hours of life in three groups of term, vaginally delivered infants, LGA infants of women with gestational diabetes (n = 20), AGA infants of women with gestational diabetes (n = 20), and AGA infants of nondiabetic women (n = 30). We excluded infants of women with hypertension, smoking, alcohol or drug abuse, and those with fetal heart rate abnormalities in labor, low Apgar scores, hemolysis, blood loss, or chromosomal anomalies. RESULTS: There were no significant differences among groups in gestational age, gravidity, parity, maternal analgesia, 1- and 5-minute Apgar scores, and lymphocyte counts. Corrected white blood cell counts and hematocrit were significantly higher in LGA infants of women with gestational diabetes than in the other groups. The median nucleated RBC count was significantly higher in LGA infants of women with gestational diabetes (0.56 x 10(9)/L, range 0-1.8 x 10(9)/L) than AGA infants of women with gestational diabetes (0.13 x 10(9)/L, range 0-0.65 x 10(9)/L) and controls (0.0005 x 10(9)/L, range 0-0.6 x 10(9)/L) (P < .001). Multiple regression analysis showed that absolute nucleated RBC count was significantly correlated with birth weight (or macrosomia) and maternal diabetic status (r2 = .25, P < .001 for the multiple regression, contribution of birth weight r2 = .19, and diabetes r2 = .06). CONCLUSION: At birth, term LGA infants born to women with gestational diabetes had higher absolute nucleated RBC counts compared with AGA infants born to women with gestational diabetes and controls.

Birth Weight↗