Species patterns: evolution's competitive edge

Phylogenetic analyses of island lizard faunas suggest that patterns in species distributions and body size evolution are the result of resource competition.     

Benefit of neurophysiologic monitoring for pediatric cardiac surgery

BACKGROUND: Pediatric patients undergoing repair of congenital cardiac abnormalities have a significant risk of an adverse neurologic event. Therefore this retrospective cohort study examined the potential benefit of interventions based on intraoperative neurophysiologic monitoring in decreasing both postoperative neurologic sequelae and length of hospital stay as a cost proxy. METHODS: With informed parental consent approved by the institutional review board, electroencephalography, transcranial Doppler ultrasonic measurement of middle cerebral artery blood flow velocity, and transcranial near-infrared cerebral oximetry were monitored in 250 patients. An interventional algorithm was used to detect and correct specific deficiencies in cerebral perfusion or oxygenation or to increase cerebral tolerance to ischemia or hypoxia. RESULTS: Noteworthy changes in brain perfusion or metabolism were observed in 176 of 250 (70%) patients. Intervention that altered patient management was initially deemed appropriate in 130 of 176 (74%) patients with neurophysiologic changes. Obvious neurologic sequelae (i.e., seizure, movement, vision or speech disorder) occurred in five of 74 (7%) patients without noteworthy change, seven of 130 (6%) patients with intervention, and 12 of 46 (26%) patients without intervention (p = 0.001). Survivors' median length of stay was 6 days in the no-change and intervention groups but 9 days in the no-intervention group. In addition, the percentage of patients in the no-intervention group discharged from the hospital within 1 week (32%) was significantly less than that in either the intervention (51%, p = 0.05) or no-change (58%, p = 0.01) groups. On the basis of an estimated hospital neurologic complication cost of $1500 per day, break-even analysis justified a hospital expenditure for neurophysiologic monitoring of $2142 per case. CONCLUSIONS: Interventions based on neurophysiologic monitoring appear to decrease the incidence of postoperative neurologic sequelae and reduce the length of stay. Inasmuch as the break-even cost for neurophysiologic monitoring is more than four times the actual average charge, both patients and hospital may profit from this service. Because this study was not a truly randomized clinical trial, unintentional statistical bias may have occurred and caution is urged in interpreting the magnitude of apparent intergroup outcome differences.     

A study of cardiovascular risk in heterozygotes for homocystinuria

Early atherosclerotic-like lesions and thromboemobolic problems are prominent in homocystinuric patients. Recent evidence suggested that mild homocyst(e)inemia, such as is present in heterozygotes for homocystinuria due to cystathionine synthase deficiency, may cause a marked excess in early ischemic heart disease. To evaluate the risk due to mild homocyst(e)inemia, the frequencies of heart attacks and strokes in parents and grandparents of homocystinuric children were assessed in the present study. No statistically significant increases in the incidence of heart attacks or strokes were consistently detected. The data available are sufficient to virtually exclude an increase in the cardiovascular risk for homocystinuria heterozygotes of as much as fivefold compared to controls, and to make very improbable a relative risk of as much as threefold. Less than 5% of homocystinuria heterozygotes are likely to have a fatal or nonfatal heart attack by age 50. These results fail to suggest that mild homecyst(e)inemia is an important contributory factor in the overall incidence of cardiovascular disease.     

Elimination of interference component in Wigner-Ville distribution for the signal with 1/f spectral characteristic

Human populations are thought to metabolize coumarin almost exclusively by 7-hydroxylation. We have identified an individual who is homozygous for a single amino acid substitution (Leu160His) in the cytochrome P450 CYP2A6 arising from the variant CYP2A6*2 allele. On administration of coumarin (2 mg orally) no detectable 7-hydroxycoumarin was excreted in the 0-8-hr urine, rather, approximately 50% of the dose was eliminated as 2-hydroxyphenylacetic acid, the end-product of coumarin 3-hydroxylation. His immediate family members, who were heterozygous for the CYP2A6*2 allele, excreted little 2-hydroxyphenylacetic acid and mainly 7-hydroxycoumarin, when similarly tested. These findings raise a question regarding human risk evaluations for environmental coumarin exposures, since 7-hydroxylation is regarded as a detoxication pathway, but 3-hydroxylation as the process required to lead to macromolecular covalent binding of coumarin. Persons homozygous for the CYP2A6*2 allele may constitute 1-25% of various populations.     

MCMI-III as a treatment outcome measure for psychiatric inpatients

The Million Clinical Multiaxial Inventory-III (MCMI-III) recently was introduced to replace and update the MCMI-II. A sample of 97 psychiatric inpatients were administered the MCMI-III shortly following admission, and again 7-10 days later. Changes in the personality and symptom scales generally paralleled those found in previous work with the MCMI-II, although the mean retest interval was considerably shorter than in the earlier study. However, some differences between the two instruments were observed, confirming the need for ongoing cross-validation work on the MCMI-III as an instrument that is distinct from the MCMI-II.     

Transforming growth factor beta 1 can induce estrogen-independent tumorigenicity of human breast cancer cells in athymic mice

We have examined the effect of transforming growth factor beta 1 (TGF-beta 1) overexpression in human breast cancer cell tumorigenicity in athymic mice. Estrogen-dependent MCF-7 cells were stably transfected with pSVTGF beta 1. A clone was isolated which overexpressed TGF-beta 1 mRNA and secreted > 10-fold more TGF-beta activity into the tissue culture medium. Similar to the parent line, the MCF-7/TGF-beta 1 cells were relatively insensitive to exogenous TGF-beta 1 and exhibited low levels of TGF-beta receptors. Clonogenicity in soft agarose, doubling time, morphology, and sensitivity to 17 beta-estradiol and the antiestrogen tamoxifen were not altered in the transfected cells. Inoculation s.c. of MCF-7/TGF-beta 1 cells in ovariectomized nude mice resulted in 100% tumor formation which was totally abrogated by i.p. administration of the neutralizing anti-TGF-beta 2G7 IgG2B. The parent cells formed tumors only after estrogen supplementation. By immunohistochemistry, higher levels of TGF-beta 1 protein were detected in MCF-7/TGF-beta 1 tumors than in estrogen-induced parent MCF-7 tumors. Administration of 1 microgram TGF-beta 1 i.p. daily for 3 weeks after tumor cell inoculation transiently supported estrogen-independent growth of parent MCF-7 tumors in castrated nude mice. These data indicate that overexpression of TGF-beta 1 in human breast cancer cells can contribute to their escape from hormone dependence.