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Biomedical subjects

G L Anderson

Publications and source records attributed to G L Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Direct visualization and measurements of wound neovascularization: application in microsurgery research.

Neovascularization or angiogenesis is an essential yet poorly understood component of the healing process. In wound healing research, there is a lack of models enabling quantitative and continuous measurements of wound neovascularization. The hairless mouse ear wound model permits quantitative measurements of wound epithelialization and neovascularization continuously throughout the healing process. On the ears of male homozygous (hr/hr) hairless mice, standardized circular full thickness dermal wounds are produced; then, using vital microscopy, these two processes are directly viewed and measured at day 0 and every third day thereafter until these are complete. This model system and its application to clinically relevant situations are reviewed.

Animals↗
PubMed1994

Microcirculatory consequences of microvascular surgery.

Although free tissue transfer success has been greatly improved by developments in operating microscopes, microsutures, microinstruments, and technique, free flap and replant failure remain a significant problem under certain adverse circumstances. The nature of these failures is often multifactorial and remains poorly understood. A greater understanding of the processes involved would provide the potential for greater pharmacological control of any adverse conditions prevailing and would thus offer the prospect of more effective adjunctive therapy in the presence of such adverse conditions. Research endeavors in this area have been hindered by the absence of good research models. The isolated rat cremaster muscle model is a recently developed model that simulates the conditions of free tissue transfer. Using this model, both thrombus formation and numerous microcirculatory parameters can be measured. The microcirculatory parameters studied to date include the formation of thromboembolism, capillary perfusion, vessel diameters, red blood cell velocity, leukocyte-endothelium interaction, and microvascular leakage. The isolated rat cremaster muscle model addresses many of the shortcomings of earlier research models and offers the promise of answering at least some of the many unanswered questions relating to free flap and replant failure.

Animals↗
PubMed1994

Direct visualization and measurement of microsurgically induced thromboembolism.

A common cause of free flap and replant failure is thrombotic occlusion of the anastomosed pedicle vessel(s). Clinical observations and subsequent experimental studies showed that platelet emboli generated at the arterial anastomosis caused significant alterations in the downstream microcirculation. To study both the thrombogenic arterial (anastomosis) site and the downstream microcirculation, we developed an animal model (the isolated rat cremaster) in which we could directly view and quantitatively analyze thrombus formation and the appearance of emboli in the downstream microcirculation. Using this model we studied the effect that reducing blood flow across the arterial anastomotic site had on thrombus formation at the anastomotic site and the appearance of emboli in the downstream microcirculation. In 40 male Sprague-Dawley rats we found that reducing blood flow velocity to approximately half of normal during reperfusion nearly eliminated emboli appearing in the downstream microcirculation compared with controls, 43.9 +/- 31.5 vs. 259.5 +/- 117.8 emboli, respectively. We also found that the same low flow had no effect on thrombus size at the pedicle artery injury site yet significantly decreased the rate at which thrombus formation occurred (time to maximum thrombus size; low flow = 25.3 +/- 8 minutes, normal flow = 6.6 +/- 3 minutes). From these studies we conclude that reducing pedicle artery blood flow in our rat model during reperfusion can protect the down-stream microcirculation from platelet emboli-induced injury; however, the same reduction in flow does not affect thrombus formation in the pedicle artery. Further studies using direct observation/measurement techniques are needed for a better understanding of the mechanisms regulating free flap and replant failure.

Anastomosis, Surgical↗
PubMed1994

Mammography screening: how important is cost as a barrier to use?

OBJECTIVES: Recent legislation will improve insurance coverage for screening mammography and effectively lower its cost to many women. Although cost has been cited as a barrier to use, evidence of the magnitude of its effect on use is limited. METHODS: Mammography use in the past 2 years among women aged 50 to 75 residing in four suburban or rural counties in Washington State was estimated from 1989 survey data. Logistic regression analysis was used to estimate the odds ratio of mammography use as a function of economic and other variables. Within a residential area, averages were used to measure the market price of mammography and the time cost to obtain a mammogram. RESULTS: Use was lower among women who faced a higher net price or who preferred to obtain a mammogram during weekend or evening hours and higher among women with higher incomes. Visiting no doctor regularly and smoking were predictors of failure to use mammography. CONCLUSION: The effects of economic variables on mammography use are important and stable across subsets of the population, but they are modest in size.

Aged↗
PubMed1994

Comparison of the effects of commonly used wound agents on epithelialization and neovascularization.

BACKGROUND: The primary effect sought with most topical wound therapy is antimicrobial. Topical wound agents are thought to promote normal healing by protecting the wound from infection. In this study, we examined the effect of six commonly used topical wound agents (bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on epithelialization and neovascularization in noninfected wounds. For this study, a new wound model was used in which direct visualization and quantification of wound epithelialization and neovascularization were carried out throughout the entire healing process. STUDY DESIGN: We measured the effect which 500 U per g of bacitracin, 0.25 percent of sodium hypochlorite, 0.5 percent silver nitrate, 1 percent silver sulfadiazine, 8.5 percent mafenide acetate, and 10 percent povodione-iodine had on the rate of wound epithelialization and neovascularization. The agents were applied topically to 99 circular full-thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male hairless mouse ears. This model enabled us to visualize and measure directly wound epithelialization and neovascularization repeatedly throughout healing, using intravital video microscopy and computerized digitized planimetry. RESULTS: Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide acetate (n = 14) epithelialized in 7.2 +/- 0.7, 7.1 +/- 0.3, and 7.3 +/- 0.3 days, respectively. This was significantly (p < 0.01) faster than the wounds treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and bacitracin (n = 13). Wounds treated with povidone-iodine epithelialized the slowest (11.8 +/- 0.55 days). Wound neovascularization was completed most rapidly in the groups treated with povidone-iodine and silver sulfadiazine (15.0 +/- 0.4 and 15.3 +/- 0.7 days, respectively). This was significantly (p < 0.05) faster than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4 +/- 0.56 days. One-half of the wounds treated with sodium hypochlorite (eight of 16) did not epithelialize or neovascularize. CONCLUSIONS: The various antimicrobial agents studied in our in vivo model affect wound epithelialization and neovascularization differently. These effects on these two very important aspects of healing should be taken into consideration when indicating a specific agent for treatment of different types of wounds.

Animals↗
PubMed1993

Experimental study of the relationship between alterations in tissue perfusion and anastomotic patency.

It is generally believed that alterations in perfusion which endanger a free flap or replant are directly related to thrombus formation and obstruction of blood flow at the anastomotic site. Recent experimental work in our laboratory suggests that the presence of platelet emboli downstream in the microcirculation might be responsible at least in part for postoperative perturbations in perfusion. To determine whether changes in tissue perfusion can occur in the absence of corresponding changes in anastomotic patency we studied microvascular blood flow in the exposed rat cremaster flap model. We made continuous measurements of both anastomotic patency and downstream microcirculatory perfusion following small vessel repair. Using this approach we found that during one hour after clamp release and reperfusion in the 10 animals studied, pedicle artery blood pressure, which indicates pedicle patency in this model, was functionally normal 97% +/- 2 of the time while blood flow in the downstream tissue (cremaster) remained normal an average of only 65% +/- 7 of the time. In most cases these flow alterations were associated with the presence of visible platelet emboli in the microcirculation. From these studies we conclude that when flap perfusion failure temporarily occurs, a microsurgeon must consider not only the anastomosis but also the downstream microcirculation when searching for a possible cause.

Anastomosis, Surgical↗
PubMed1993

Statistical design and monitoring of the Carotene and Retinol Efficacy Trial (CARET).

CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials.

Aged↗
PubMed1993

Effects on response rates and costs of stamps vs business reply in a mail survey of physicians.

In the general population, the use of stamps rather than business reply postage significantly improves response rates in mail surveys. Among physicians, however, a smaller effect might be anticipated due to their greater sophistication. An experiment was conducted to test the hypothesis that stamps would improve response rates and lower costs in a physician survey that included intensive follow up. In 1989, 380 physicians who reported providing primary care were surveyed. The protocol included two mailings, a postcard reminder, and two telephone reminders. Physicians were randomly assigned to receive a return envelope with a first-class stamp or an envelope that had been preprinted "business reply mail" in the first and second mailings. Response rates, calculated as completed surveys divided by eligible physicians, were 83.8 and 72.1% for stamps and business reply respectively, a difference of 11.7 percentage points (p < 0.01). Moreover, the total cost per completed survey was $11.18 for the physicians receiving stamps and $14.25 for the physicians receiving business reply. As in mail surveys of the general public, the use of first-class stamps on return envelopes both improves response rates and reduces cost in surveys of physicians.

Data Collection↗
PubMed1993

The effects of heparin and dietary fish oil on embolic events and the microcirculation downstream from a small-artery repair.

In recent studies we demonstrated that platelet emboli induced by arterial injury impair the microcirculation. The present study was performed to determine if heparin or dietary cod liver oil reduces the incidence of emboli following the same arterial injury and, in turn, whether these agents prevent the associated decrease in microcirculatory blood flow. The cremaster muscle of 29 male Sprague-Dawley rats was isolated on a single neurovascular bundle consisting of the iliac artery and vein and the genitofemoral nerve. Emboli were generated by a thrombogenic injury of the iliac artery, and their number and their subsequent effect on capillary perfusion in the downstream microcirculation were measured. Nine animals received heparin (10-unit IV bolus plus 10 units/hour IV infusion), 10 were fed cod liver oil (10 percent by weight of food) for 3 weeks prior to the experiment, and 9 animals receiving no treatment served as controls. The number of emboli was significantly reduced in the heparin group, but there was no accompanying improvement in capillary perfusion. In contrast, in the cod liver oil group, the number of emboli was not reduced, but there was significant improvement in capillary perfusion. These findings suggest that the harmful effect that platelet emboli have on the microcirculation is probably biochemical in nature (vasoconstriction) rather than related to simple mechanical obstruction to flow.

Anastomosis, Surgical↗
PubMed1993

Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation.

PURPOSE: Hepatic venoocclusive disease (VOD) is a common complication of cytoreductive therapy for marrow transplantation. Only 25% of patients who develop VOD have severe disease. We tested the hypothesis that early clinical signs of VOD would predict which patients would recover and which would die. PATIENTS AND METHODS: We evaluated 355 consecutive patients who had transplants between August 6, 1987 and July 21, 1988 for occurrence of VOD and whether it was reversible within 100 days of transplant. Total serum bilirubin and weight gain from day -7 through day +16 posttransplant were compared among patients with no, severe, or nonsevere VOD. Logistic regression models were developed to estimate probabilities of severe VOD at each of six time intervals. The accuracy of these models was tested by applying them to 392 consecutive patients who underwent transplantation between July 22, 1988 and July 20, 1989. RESULTS: As early as day -1, bilirubin and weight gain were significantly different between patients whose VOD proved to be severe and patients with reversible VOD or no disease. Regression models were used to generate coefficients (beta 0, beta 1, beta 2) for the equation P = 1/(1 + e-z), where P is the probability of severe VOD and z = beta 0 + beta 1 (In total serum bilirubin [mg/dL]) + beta 2 (percent weight gain). Application of this equation to the next 392 patients allowed us to calculate sensitivity, specificity, and positive predictive value for a range of probabilities. CONCLUSION: The course of VOD after cytoreductive therapy can be predicted by knowing the serum bilirubin and weight gained within 1 to 2 weeks of transplantation. Probability estimates derived from patient data are highly specific and moderately sensitive. Such probability estimates may be useful when considering potentially risky interventions to treat VOD, such as recombinant human tissue plasminogen activator.

Adolescent↗
PubMed1993

Splanchnic resuscitation: a strategy for preventing liver failure in sepsis.

Liver failure is commonly encountered in the critically ill, septic patient. This hepatic dysfunction occurs as a wide spectrum of abnormalities, ranging from mild chemical derangements to fulminant liver failure. The syndrome of multiple system organ system failure due to sepsis is often complicated by alterations in splanchnic/hepatic function. Knowledge of gut pathophysiology with resultant changes in substrate metabolism, synthetic function, cytokine release, and the detrimental effects on other organ systems is rapidly expanding. The functions of these pathophysiologically produced factors include extensive autocrine, paracrine, and endocrine effects. Evidence suggests that adequate resuscitation during sepsis, which is measured by systemic end-points, may result in inadequate splanchnic blood flow and oxygen delivery. The addition of serial measurements of splanchnic end-points may limit the hepatic failure encountered in multiple system organ failure due to sepsis.

Animals↗
PubMed1993

Chloride alters renal blood flow autoregulation in deoxycorticosterone-treated rats.

Renal blood flow autoregulation was studied in deoxycorticosterone acetate (DOCA)-treated rats. DOCA pellets (75 mg) were implanted in uninephrectomized rats, and the animals were then fed one of four diets: (1) normal sodium chloride level, (2) high in NaCl, (3) high in chloride, or (4) high in sodium. After 40 to 45 days of the DOCA-diet treatment, animals were subjected to renal blood flow autoregulation experiments; an inflatable aortic occluder was placed proximal to the renal artery, and renal blood flow (electromagnetic flow probe) was measured while renal perfusion pressure was reduced from normal (in that animal) to 20 mm Hg, in 10 mm Hg decrements to determine the lower threshold of autoregulation. Directly measured arterial blood pressure was higher in the DOCA-high NaCl group compared with the DOCA-normal NaCl group (127 +/- 3 mm Hg vs 103 +/- 4 mm Hg) during anesthesia. Significant elevation of lower autoregulatory thresholds were demonstrated in both the DOCA-high NaCl (98 +/- 7 mm Hg) and high chloride groups (94 +/- 3 mm Hg) compared with the DOCA-normal NaCl (77 +/- 4 mm Hg) and the DOCA-high sodium (76 +/- 5 mm Hg). Pressure-flow curves of the DOCA-high chloride groups were shifted significantly downward (reduced renal blood flow at all pressures) and rightward (elevated lower threshold) compared with the DOCA-normal NaCl and -high sodium groups. These data indicate that DOCA-treated rats consuming a diet high in chloride have altered renal blood flow autoregulatory mechanisms.

Animals↗
PubMed1993

Effect of DMSO exposure without cryopreservation on hematopoietic progenitor cells.

Colligative cryoprotectants must be non-toxic at the high concentrations required for protection of cells from freeze-injury. Human hematopoietic stem cells are usually cryopreserved in a solution containing 1.6 molal (10% v/v) DMSO. We studied the chemical toxicity of this agent to myeloid and erythroid progenitor cells from healthy donors. No DMSO toxicity was found at concentrations of 5% or 10% at either 4 degrees or 37 degrees C for incubation durations up to 1 h. DMSO at 20% did not decrease the number of progenitor cell-derived colonies per 5 x 10(4) cells cultured, but did result in cell clumping during DMSO washout, resulting in a net loss of progenitor cells. At a concentration of 40% DMSO, a direct toxicity to hematopoietic progenitors was found. Delay in removal of DMSO after thawing of cryopreserved cells for periods up to 1 h was also non-toxic to hematopoietic progenitor cells. Direct addition of DMSO at 1% or 10% final concentration (v/v) to the culture dishes suppressed colony formation. These data suggest that DMSO is not toxic to haematopoietic progenitor cells after short-term exposure at the concentrations used for cryopreservation of marrow and peripheral blood stem cells.

Cell Aggregation↗
PubMed1992

The purification and characterization of arsenite oxidase from Alcaligenes faecalis, a molybdenum-containing hydroxylase.

The purification and initial characterization of arsenite oxidase from Alcaligenes faecalis are described. The enzyme consists of a monomer of 85 kDa containing one molybdenum, five or six irons, and inorganic sulfide. In the presence of denaturants arsenite oxidase releases a fluorescent material with spectral properties identical to the pterin cofactor released by the hydroxylase class of molybdenum-containing enzymes. Azurin and a c-type cytochrome, both isolated from A. faecalis, each serves as an electron acceptor to arsenite oxidase and may form a periplasmic electron transfer pathway for arsenite detoxification. Full reduction of arsenite oxidase requires 3-4 reducing equivalents, using either arsenite or dithionite as the electron source. Below 20 K, oxidized arsenite oxidase exhibits an EPR signal with g values of 2.03, 2.01, and 2.00, which integrates to approximately 0.4 spins/protein. Since enrichment in 57Fe results in broadening of this EPR signal, the center giving rise to this signal must contain iron. The most plausible candidates are a [4Fe-4S] high potential iron protein center or a [3Fe-4S] center. The EPR signal observed in oxidized arsenite oxidase disappears upon reduction of the protein with either arsenite or dithionite. Concomitantly, a rhombic EPR signal (g = 2.03, 1.89, 1.76) appears which is similar to that of Rieske-type [2Fe-2S] clusters and spin quantifies to one spin/protein.

Alcaligenes↗
PubMed1992

Correlates of maintenance of a low-fat diet among women in the Women's Health Trial.

BACKGROUND: The Women's Health Trial (WHT) was a feasibility study for a randomized controlled trial designed to test the hypothesis that a reduction in dietary fat reduces breast cancer incidence among women age 45 to 69. Between 1984 and 1988, 2,064 women participated in its two phases. METHODS: A follow-up study of 525 women who were randomized to receive the WHT dietary intervention program was conducted to assess maintenance of the diet 1 year on average after the trial ended. Among 448 participants, the mean percentage of energy from fat as measured by a food frequency questionnaire was 40.0% at baseline, 26.3% at the end of the trial, and 27.7% at follow-up. Based on 408 women with complete data, a recursive model was estimated, describing the influence of baseline characteristics of the women on attendance at intervention program sessions, adherence to the diet during the trial, and long-term maintenance of the diet after the trial ended. The effects of women's experiences during the trial on adherence and long-term maintenance were investigated as well. RESULTS: Attendance at the educational sessions was strongly related to adherence to the diet during the trial (P less than 0.001), and adherence was the most important predictor of long-term maintenance (P less than 0.001). The percentage of energy from dietary fat at baseline was an important correlate of both adherence (P less than 0.001) and long-term maintenance (P less than 0.001). College-educated women were more likely to adhere to the diet during the trial (P less than 0.001). Feelings of deprivation adversely affected long-term maintenance (P less than 0.01), primarily through their effect on adherence during the trial (P = 0.01). Costliness of the diet in time and money negatively influenced long-term maintenance (P less than 0.05). Development of a distaste for fat encouraged adherence (P = 0.06). CONCLUSIONS: The low-fat dietary pattern established during the WHT was maintained for as long as 20 months after the trial ended. A recursive model was useful in analyzing the process and correlates of long-term maintenance of dietary behavior change. Both predisposing variables and women's experiences while on a low-fat diet were associated with long-term maintenance. The results suggest that feelings of deprivation should be avoided, perhaps by use of low-fat substitutes, by those attempting to lower their dietary fat and that more research is needed on the development of a distaste for fat among individuals who adopt low-fat diets.

Aged↗
PubMed1992

Assessment and treatment strategies for depressive disorders commonly encountered in primary care settings.

Frequently overlooked, depression is a very common complex disorder that causes significant morbidity and mortality. This article provides a review of three commonly encountered depressive disorders in primary care settings: adjustment disorder with depressed mood, dysthymia and major depression. Since many individuals minimize the affective symptoms of depression, clinicians must maintain a high index of suspicion when clients present with vague somatic complaints, such as fatigue, headache, constipation and difficulty sleeping. To reach an accurate diagnosis, a thorough history, physical examination and appropriate laboratory studies should be performed. Numerous rating scales are presented to aid assessment. Common intervention strategies for the treatment of depressive disorders include education, drug therapy, and supportive individual and family counseling.

Antidepressive Agents↗
PubMed1992

Serotype prevalence of Candida albicans from blood culture isolates.

Blood culture isolates of Candida albicans were collected from 102 patients in Seattle, Wash., hospitals (n = 77) and Hong Kong (n = 25). The patients were classified by immune status into two groups. Group I patients were severely immunosppression, and group II patients had underlying risk factors for candidemia but no underlying immunosuppression. Serotyping by Hasenclever tube agglutination was done. In the Seattle area, the odds of fungemia with type B C. albicans were 3.62 times greater than the odds of type B fungemia in group II patients. Although the odds ratio could not be computed for Hong Kong patients, the direction of the relationship in this population was consistent with the data on Seattle patients. Despite the magnitude of the odds ratios, the relative prevalence of type B over type A in group I compared with group II was not significant when analyzed separately by region, probably because of relatively low numbers of isolates in group II. Accepting that the effect of immune status on serotype is equivalent across regions but presupposing that a regional effect on type B prevalence exists, the pooled odds for fungemia with serotype B in group I patients are increased 5.4-fold over those of group II patients. Logistic regression analysis controlling for region gave similar results.

Adult↗