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Biomedical subjects

D Ferguson

Publications and source records attributed to D Ferguson.

At least 91 records · Page 5Linked to original sources

Intestinal villus microcirculatory response to hemorrhage in adult and immature rats.

The response of the villus microcirculation to moderate hemorrhage was compared in adult and immature rats. As an estimate of villus blood flow, flux of red blood cells through the terminal arteriole loop at the villus tip was quantified in vivo using fluorescence epilumination videomicroscopy. Baseline red blood cell flux and mean arterial pressure (MAP) of immature rats (973 cells/s, 84 mm Hg) were significantly less than that of adults (1,435 cells/s, 131 mm Hg). Following hemorrhage of 30% of estimated blood volume, MAP of immature rats was still 24% less than that of adults; however, villus flux was not significantly different (578 cells/s immature, 640 cells/s adult; P = .63). Thus, as indicated by changes in villus flux, immature rats do not appear to be more susceptible to acute intestinal blood flow reduction induced by a single moderate hemorrhage. Immaturity of villus microvascular anatomy and of intestinal vasoregulatory mechanisms may account for the differential response.

Age Factors↗

Multicenter, randomized, double-blind, placebo controlled study to investigate the effect of finasteride (MK-906) on stage D prostate cancer.

A total of 28 untreated patients with asymptomatic, stage D prostate cancer was randomized in a double-blinded fashion to receive finasteride (10 mg. per day), a 5 alpha-reductase inhibitor or placebo. Patients were evaluated at 3-week intervals by rectal examination, and serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) levels, and at 6-week intervals by bone scan and transrectal ultrasound determinations of prostatic volume. Patients stopped the medication at week 6 at the discretion of the investigator when PSA levels increased from baseline. After 12 weeks all patients were reevaluated. Of the patients 13 received finasteride and 15 received placebo. The 2 groups did not differ statistically with respect to patient age, initial PSA and PAP level, or the extent of metastases on initial bone scan. A statistically significant decrease in the median percentage change from baseline in PSA at weeks 3 and 6 occurred in the finasteride group compared to the placebo group (-22.9% versus -2.9% and -15.1% versus +11.7%, respectively, p less than 0.05). Finasteride had no effect upon PAP, serum testosterone, prostatic volume or appearance of bone scans. A decrease in serum PSA in the finasteride treatment group suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration yet because of the potency preserving feature and the lack of toxicity finasteride may warrant further study in the treatment of prostate cancer.

5-alpha Reductase Inhibitors↗

Dietary glucose and fat attenuate effects of adrenalectomy on energy balance in ob/ob mice.

The body energy balance response of ob/ob mice to adrenalectomy is diet dependent. Diets varying in source of carbohydrate (starch, glucose or fructose), fat to starch ratio, or fat to glucose ratio were fed to determine influences on energy balance in female adrenalectomized ob/ob mice. Adrenalectomy lowered food intake in all ob/ob mice to values comparable to those of lean mice independent of diet, but the percentage of dietary energy retained as body energy in adrenalectomized ob/ob mice was lowered to values comparable to those of lean mice only in mice fed starch or fructose, not in mice fed glucose or fat. Consumption of either high glucose or high fat diets blocked about one-half the overall effect of adrenalectomy on energy balance in ob/ob mice. Hyperinsulinemia was associated with the high efficiency of energy retention observed in adrenalectomized ob/ob mice fed glucose, but high efficiency of energy retention occurred in adrenalectomized ob/ob mice fed high fat diets without concomitant hyperinsulinemia. Adrenalectomy-induced changes in brain weight and protein content, body protein content and plasma thyroid hormone concentrations in ob/ob mice were independent of diet consumption. Combined adrenalectomy-ovariectomy diminished, but did not eliminate, the diet-dependent influences on energy balance in ob/ob mice. In conclusion, dietary glucose and dietary fat both attenuate effects of adrenalectomy on energy balance in ob/ob mice by promoting high efficiencies of energy retention.

Administration, Oral↗

Conjugated desferoxamine attenuates hepatic microvascular injury following ischemia/reperfusion.

Iron-dependent oxy radicals have been implicated in reperfusion injury. Although the iron chelator desferoxamine (DFO) is beneficial, its hemodynamic effects and short vascular retention limit its use in vivo. We tested whether DFO conjugated to a high-molecular-weight starch might ameliorate in vivo hepatic microvascular injury without adverse side effects following 120 min of ischemia. Prior to reperfusion, conjugated DFO (100 mg/kg), vehicle (Veh), or saline (I/R) was administered. After 90 min of reperfusion, blood was collected for serum transaminase determination (ALT; U/liter), and fluorescein-albumin was injected to label perfused microvessels, which were quantified in frozen sections by a point-count technique. Tissue edema was estimated by wet to dry weight ratios (W/D). Reperfusion results in hepatocyte injury (rise in ALT and W/D) and a 30% loss of perfused microvessels. Intravenous administration of conjugated DFO produces no significant change in systemic hemodynamics, whereas both ALT and tissue edema were decreased by approximately 50%. Moreover, perfused microvessels were restored virtually to nonischemic control levels. Enhanced perfusion and attenuated cell injury with DFO suggest that microvascular failure and resultant cell death are mediated, at least in part, by iron-dependent mechanisms in reperfusion.

Animals↗

Asbestos: insufficient action, overreaction, action for tomorrow.

The toll of death and disability associated with the inhalation of asbestos dust has often produced irrational demands for the substance to be removed from buildings. This article considers what approaches should now be adopted with a view to protecting people from exposure to asbestos.

Asbestos↗

Prolongation of anesthesia with xylazine, ketamine, and guaifenesin in horses: 64 cases (1986-1989).

On 74 occasions, 54 horses and 6 foals were anesthetized with xylazine and ketamine or xylazine, guaifenesin, and ketamine, with or without butorphanol. On 64 occasions, anesthesia was prolonged for up to 70 minutes (34 +/- 15 min) by administration of 1 to 9 supplemental IV injections of xylazine and ketamine at approximately a third the initial dosage. All horses except 5 were positioned in lateral recumbency, and oxygen was insufflated. In adult horses, the time from induction of anesthesia to the first supplemental xylazine and ketamine injection was 13 +/- 4 minutes and the time between supplemental injections was 12.1 +/- 3.7 minutes. These results were consistent with predicted plasma ketamine concentration calculated from previously published pharmacokinetic data for ketamine in horses. Respiratory and heart rates and coccygeal artery pressure remained consistent for the duration of anesthesia. The average interval between the last injection of ketamine and assumption of sternal position was approximately 30 minutes, and was the same regardless of the number of supplemental injections. The time to standing was significantly longer (P less than 0.05) in horses given 2 supplemental injections, compared with those not given any or only given 1, but was not longer in horses given 3 supplemental injections. Recovery was considered unsatisfactory in 5 horses, but did not appear to be related to prolongation of anesthesia.

Anesthesia↗

Comparison of University of Wisconsin (UW) and Eurocollins (EC) preservation solutions in a rat liver transplant model.

The Eurocollins (EC) and University of Wisconsin (UW) preservation solutions were compared in a rat liver transplant model. After hepatectomy, 48 rat livers were flushed with either EC or UW preservation solution and were randomly assigned to 1, 12, 24, and 30 h of preservation at 4 degrees C, resulting in eight groups each containing six livers. Following preservation, orthotopic liver transplantation with reconstruction of the hepatic artery was performed. The efficacy of the preservation solution was assessed at 48 h post-transplantation by survival histological features and aspartate transaminase assay (AST) values. None of the rats survived 30 h of liver preservation with EC whereas five out of six rats did with UW preservation. After 24 h of liver preservation, three of the six rats in the EC group survived, compared to all six rats in the UW group. Histological evidence of severe ischemia was found in both groups in all but one survivor (UW, 24 h). After 12 h of EC preservation, one rat died within 48 h and severe ischemic changes were found in the remaining five rats. Among the rats with 12 h of UW preservation, only two out of six showed ischemic changes, and all six rats survived beyond 48 h. Without preservation (1 h), ischemic damage was found in two out of six rats in each group and all rats survived. The median AST values were higher in the EC groups than in the UW groups; the difference became significant after 12-h preservation (EC 900 IU/l versus UW 465 IU/l) and 24-h preservation (EC 5220 IU/l versus UW 631 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

The GLN3 gene product is required for transcriptional activation of allantoin system gene expression in Saccharomyces cerevisiae.

We show that mutation at the GLN3 locus results in decreased steady-state levels of DAL7, DUR1,2, CAR1, and URA3 mRNAs derived from cultures grown in the presence of inducer. Basal levels of these RNA species, however, were not significantly affected by a gln3 mutation. The GLN3 product appears to affect gene expression in two ways. The pleiotropic requirement of GLN3 for induced gene expression probably derives from the need of the GLN3 product for inducer uptake into the cell and its loss in gln3 mutants. We also demonstrate that transcriptional activation, mediated by the DAL5 and DAL7 upstream activation sequences, requires a functional GLN3 gene product. This observation identified transcriptional activation as the most likely point of GLN3 participation in the expression of allantoin system genes.

Allantoin↗

Organ maintenance of human sebaceous glands: in vitro effects of 13-cis retinoic acid and testosterone.

Human sebaceous glands were isolated by shearing, and maintained for 7 days either on defined medium, on medium supplemented with 3 microM-testosterone or on medium supplemented with both 3 microM-testosterone and 1 microM-13-cis retinoic acid. Freshly isolated glands retained their in vivo morphology. On maintenance, the glands retained their freshly isolated rates of cell division, but the sebocytes showed increased keratinization and there was multilayering of the peripheral undifferentiated cells. However, glands maintained in the presence of 1 microM-13-cis retinoic acid showed very little luminal keratinization and only a small degree of multilayering. On autoradiography, freshly isolated glands retained their in vivo pattern of [methyl-3H]thymidine incorporation. Similar patterns were seen when glands were maintained for 7 days with or without testosterone. However, in the presence of both testosterone and 13-cis retinoic acid there was only slight graining. Following 7 days maintenance the rate of lipogenesis fell significantly. This was partially reversed by testosterone, but further inhibited by 13-cis retinoic acid. The patterns of lipids that are synthesised after a week's maintenance are very similar to those seen in freshly isolated glands, except that the squalene:cholesterol ratio is reversibly regulated by 3 microM-testosterone and 1 microM-retinoic acid. Protein synthesis was maintained at the same rates as for freshly isolated glands under all conditions of maintenance. Whereas DNA synthetic rates were maintained in the presence of testosterone, they were significantly inhibited by 13-cis retinoic acid. Glandular wet weights were retained under all conditions of maintenance, except that they were significantly reduced by 13-cis retinoic acid. This study shows that human sebocytes continue to divide on organ maintenance, but that they do not differentiate fully. However, this provides the first demonstration that 13-cis retinoic acid acts on human sebaceous glands directly, reducing the rate of cell division and the rate of lipogenesis, which shows that the maintained human sebaceous gland might provide a useful model for studying the effect of 13-cis retinoic acid on human sebocytes.

Adult↗

How effectively are osteopathic medical students coping with a stressful life-style?

Medical education has been described as an extremely intense and stressful experience. First- and second-year osteopathic medical students (N = 225) were surveyed to assess their perceptions of their own physical and psychological well-being, mechanisms they use to combat daily stress, their leisure activities, and the health-promoting behaviors in which they engage. This study found perceived physical and psychological well-being to be quite good, with more than 82% of respondents reporting "good" or "excellent" in both areas. Only 11% of students reported using tobacco, and the mean number of alcoholic drinks consumed per day was less than one. Most of the students reported that they exercised regularly and that they did not view sleep deprivation as a significant problem; however, the students did perceive the stress attributed to the demands of medical school as quite high. The primary coping behaviors they used in response to stress included humor, leisure, exercise, and social activity. Smoking, using medication, and using illicit drugs were infrequently indicated as coping strategies. From a comprehensive perspective, student perceptions indicate that they are effectively coping with the stresses of medical education.

Adaptation, Psychological↗

Malacoplakia of the urethra.

We report a case of urethral malacoplakia associated with disease of the bladder and bladder neck. Treatment consisted of fulguration of the bladder lesions and excision of the urethral lesion. Unlike most other cases of genitourinary malacoplakia, which are associated with chronic urinary tract infection, this patient had sterile urine and no history of urinary tract infections. Urethral malacoplakia is reviewed, and the pathogenesis and treatment of the disease are discussed.

Female↗

Bovine bone morphogenetic protein (bBMP) fraction-induced repair of craniotomy defects in the rhesus monkey (Macaca speciosa).

Large cranial defects do not always heal spontaneously, especially in humans; often they have to be obturated with metallic or acrylic fillers. Bilateral cranial trephine defects, measuring 14-20 mm in diameter, were created in three Rhesus monkeys, providing a typical primate model system for investigations in comparative physiology of bone regeneration. Each skull had one control and one experimental trephine defect. Control defects were implanted with bovine serum albumin (BSA). Experimental defects were implanted with 100-200 mg of a partially purified fraction of bovine bone morphogenetic protein (bBMP) in two monkeys. In one monkey, the BMP was incorporated in a 1:1 poly(lactic) poly(glycollic) acid copolymer, high-viscosity formula. The animals were killed at eight weeks, ten weeks, and 16 weeks after implantation. The tissue responses were analyzed by computed histomorphometry and routine histologic examination. At each time interval, the BMP implanted defects produced more complete regeneration than the control implants. The morphogenetic response occurred in the following sequences: mesenchymal cell proliferation, chondrogenesis, and increased bone formation. BMP-induced osteogenesis may initiate the regenerative process. The copolymer releases BMP but may constitute a barrier to the end stages of replacement by new bone, and would be more useful in a low-viscosity rapidly biodegradable form.

Animals↗