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Biomedical subjects

T Manning

Publications and source records attributed to T Manning.

At least 19 recordsLinked to original sources

Role of extracellular signal-regulated kinase and phosphatidylinositol-3 kinase in chemoattractant and LPS delay of constitutive neutrophil apoptosis.

The present study examined the role of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3 kinase-stimulated Akt (PI-3K/Akt) in the regulation of constitutive human neutrophil apoptosis by bacterial lipopolysaccharide (LPS) and two chemoattractants, fMLP and leukotriene B(4) (LTB(4)). LPS and LTB(4) inhibited apoptosis, while fMLP had no effect. Inhibition of extracellular signal-regulated kinase (ERK) with PD098059 significantly inhibited the anti-apoptotic effect of both LPS and LTB(4), while inhibition of p38 kinase with SB203580 had no effect. Inhibition of PI-3K with wortmannin and LY294002 significantly attenuated the anti-apoptotic effect of LTB(4), but not LPS. LPS, fMLP, and LTB(4) stimulated similar levels of ERK and Akt activation. LTB(4) and LPS inhibited neutrophil apoptosis when added simultaneously with fMLP, and LTB(4) and LPS demonstrated an additive effect. We conclude that the ERK and/or PI-3K/Akt pathways are necessary, but not sufficient, for LPS and LTB(4) to delay apoptosis, but other anti-apoptotic pathways remain to be identified.

Androstadienes↗

Alkaline phosphatase isoenzymes and clinical features in hypophosphatasia.

Hypophosphatasia is an hereditary disease characterized by low activity of total serum alkaline phosphatase (TALP) accompanied by a range of skeletal diseases. We have measured the main circulating alkaline phosphatase isoenzymes--bone (BALP), liver (LALP), intestinal (IALP), placental (PALP)--in six families with hypophosphatasia, using kinetic and electrophorectic methods. Our observations show that patients with skeletal disease tend to have a very low BALP activity. Patients even with undetectable LALP activity do not appear to manifest any clinical complications. Patients also showed proportionately high IALP activity. Since the production of significant IALP activity is not a constant feature in all healthy individuals, it remains to be established whether the survival of one of these patients (IALP > 80% of TALP) depended on the presence of circulating IALP.

Adult↗

Preconsultation education promoting breast cancer screening: does the choice of media make a difference?

BACKGROUND: Multimedia technology can be a valuable resource for health promotion and patient education initiatives because it allows messages to be presented within an environment that is both sensory-rich and interactive (i.e., the user can explore the information according to his or her particular needs and interests). Using clinic waiting time as an opportunity for breast cancer education, this investigation examined whether an educational intervention promoting breast cancer screening would be more effective when using interactive multimedia than when using written materials. METHODS: Over a five-month period, 108 women (40-70 years of age) from two clinics (a family practice clinic and a free clinic for the poor) participated in the study. Participants initially completed measures assessing perceptions of the personal importance of breast cancer, knowledge, and anxiety about screening procedures. They then were randomly assigned to receive breast cancer education by using an interactive multimedia program or by reading a brochure. Following the intervention, the participants once again completed the perceived importance, knowledge, and anxiety measures, and evaluated the educational materials. RESULTS: These women perceived breast cancer to be a more personally important health issue, learned more, and reported less anxiety about cancer screening following the intervention regardless of method. Younger women learned more from the educational materials than did older women. Although the multimedia program received more favorable evaluations than the brochure, this effect was mediated by the message recipient's age, as younger women responded more favorably to the multimedia materials than did older women. CONCLUSION: Preconsultation education is a valuable but rarely used opportunity to promote breast cancer screening. If well constructed, educational materials using a variety of media can be effective. While preferences for media may in part depend on the audience's age, considerably more research is needed to better understand how the interplay of media, message, and audience characteristics can help accomplish health-promotion objectives.

Adult↗

Effects of age, density, and geometry on the bending strength of human metatarsals.

In this basic study, we investigated the relative roles of donor age, bone density, and bone geometry in determining structural strength of human metatarsals tested in a four-point bending configuration. Density measurements were made noninvasively using dual energy X-ray absorptiometry, and geometric measurements were made by digitally imaging cross-sections of specimens. Correlations between area bone mineral density and metatarsal strength were strong (r2 = 0.83, 0.81 for second and third metatarsals, respectively) and were not improved by including cross-sectional area or minimum moment of inertia in multiple regression analyses. Increased donor age was associated with decreased bending strength (r2 = 0.51 and 0.45, respectively), which was expected because increased age correlated significantly with decreased bone density (r2 = 0.69 and 0.80, respectively). These results indicate that the strength of human metatarsals generally decreases with age and that this decrease is likely attributable to decreased bone density. Moreover, the results indicate that noninvasive dual energy x-ray absorptiometry measurements of metatarsal density are useful for assessing metatarsal strength and that additional measurements of bone geometry are not required.

Absorptiometry, Photon↗

Motivation to participate, exercise affect, and outcome behaviors toward physical activity.

Recently researchers have focused attention on understanding the relationship between motivation to participate and affective states associated with adherence to exercise and psychological outcomes of participation. It was hypothesized that intrinsic motivation toward an activity will heighten the associated positive affect, thereby leading to increased participation and higher perceived competence and satisfaction. The presently devised models tested the above hypothesis with 130 college students enrolled in psychology classes. They were asked to complete the Motivation for Physical Activity Measure, the Sport Enjoyment Questionnaire, and general demographic questions assessing adherence to exercise and perceived competence and satisfaction. Partial support for these path models was shown as intrinsic motivation was a predictor of affect and perceived competence and satisfaction, while extrinsic motivation predicted adherence for men only. These results provide a model to enhance the understanding of exercise-related behavior in the general population and the study of the relationship of motivation with affect toward exercise.

Adolescent↗

Increasing patient involvement in choosing treatment for early breast cancer.

BACKGROUND: This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions. METHODS: Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation. RESULTS: College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure. CONCLUSIONS: Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians.

Adult↗

Comparative study of wound healing in porcine skin with CO2 laser and other surgical modalities: preliminary findings.

BACKGROUND: The CO2 laser is a common surgical modality in dermatology. To clarify conflicting reports on the histological healing properties of CO2 laser on incisional or ablative wounds, we have applied it in a miniature hairless porcine skin model at power settings similar to those used in clinical practice. METHODS: Histological parameters of wound healing in skin incisions using the CO2 laser were compared with those using scalpel, hot scalpel, and electrosection, and in dermal ablation using CO2 laser, fraize, wire brush, and electrofulguration alone or with curettage. RESULTS: In incisional wounds, tissue damage was most extensive in CO2 laser wounds, with delayed dermal healing and reepithelialization. In ablative wounds, CO2 laser caused a similar degree of tissue damage as did the electrosurgical modalities, and more damage than did fraize or wire brush. Reepithelialization was complete in CO2 laser, fraize, and wire brush wounds before electrosurgical wounds. Final histology of both incisional and ablative wounds at 6 weeks was similar with all surgical modalities. CONCLUSION: The CO2 laser and electrosurgery both produce greater focal tissue damage in incisional and ablative applications than the other modalities. Delayed epithelialization of the wound occurs with both modalities in incisional wounds but only with electrosurgery in ablative wounds. At 6 weeks, the appearance of the scar in all incisional and ablative modalities is similar grossly and histologically. Confirmation of these findings requires standardization of power density of the CO2 laser in incision and ablation.

Animals↗

Evaluation of human bone morphogenetic protein 2 in a canine spinal fusion model.

The efficacy of purified recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a porous biodegradable copolymer, poly [D,L (lactide--coglycide)] (PLGA) was evaluated using a canine posterior segmental spinal fusion model. rhBMP-2/PLGA was compared to autogenous cancellous bone and to PLGA alone. Thirty three fusion sites in 11 beagle dogs were evaluated at 12 weeks for union and mechanical strength. Union score and mechanical testing showed no difference between autogenous cancellous bone and rhBMP-2/PLGA. Union scores for autogenous cancellous bone and rhBMP-2/PLGA sites were superior to those with PLGA alone (p = 0.001 and p = 0.0007, respectively). These findings suggest that synthetic bone graft substitute materials delivering purified rhBMP-2 may be suitable for posterior spinal fusions. The use of such materials may provide efficacy equivalent to autogenous cancellous bone and avoid the morbidity associated with the harvest of autogenous graft.

Animals↗

Effects of accidental trauma on cytokine and endotoxin production.

OBJECTIVE: To determine the effects of accidental injury of varying severity on interleukin (IL)-1 alpha, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and endotoxin release. DESIGN: Prospective, multi-unit, longitudinal study. SETTING: Emergency Departments and intensive care units of two university hospitals. PATIENTS: Trauma patients after mild, moderate, and severe injury (Injury Severity Score of < or = 10, 11 to 24, and > or = 25, respectively). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma cytokine and endotoxin concentrations were measured over a 5-day period, starting within 2 hrs of accidental injury. An enzyme-linked immunosorbent assay was used to determine plasma concentrations of IL-1 alpha, IL-6, IL-8, and TNF-alpha. Plasma endotoxin concentrations were measured using a chromogenic limulus amebocyte assay. Preresuscitation samples obtained immediately on arrival in the Emergency Department, and within 2 hrs of injury, demonstrated significant increases of IL-6 and IL-8 concentrations in the severe injury group, in contrast to minimal increases seen after mild or moderate injury. Analysis of serial postresuscitation samples demonstrated rapid increases in IL-6 and IL-8 concentrations within 12 hrs of injury. IL-6 and IL-8 remained increased for 24 hrs after injury, then decreased markedly from their peak values during the next 24 hrs. Increased circulating concentrations of these cytokines continued to be present for > 5 days in the severely injured patients. IL-6 and IL-8 concentrations were only minimally increased in patients 8 and 24 hrs after moderate injury. Endotoxin and IL-1 alpha were not found in any samples, including those samples obtained serially from severely injured patients. No patient at any time point had TNF-alpha concentrations of > 35 pg/mL. CONCLUSIONS: These results demonstrate that severe injury produces rapid, large increases in circulating concentrations of IL-6 and IL-8 that may contribute to the frequent development of the adult respiratory distress syndrome and multiple organ system failure in this clinical setting.

Adult↗

Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage.

Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.

Administration, Topical↗

Role of cattle in the epidemiology of tick-bite fever in Zimbabwe.

Almost 100% of 52 cattle tested from the southern areas of Zimbabwe were found to have antibodies reactive with Rickettsia conorii compared with less than 30% of 120 cattle from the north. Steers artificially infected with R. conorii isolated from Amblyomma hebraeum were found to show no hematological or biochemical signs of disease but did seroconvert. Clinical signs of infection were restricted to regional lymphadenopathy and dermal erythema, edema, and tenderness at the inoculation site. Rickettsemia was detectable for at least 32 days postinfection. Our findings indicate that cattle could be involved in the transmission of rickettsias by A. hebraeum and may serve as a reservoir of human tick-bite fever in southern Africa.

Animals↗

The relationship between ARDS, pulmonary infiltration, fluid balance, and hemodynamics in critically ill surgical patients.

Hypervolemia from fluid overload with resultant pulmonary edema is thought to be a frequent cause of Adult Respiratory Distress Syndrome (ARDS). However, ARDS may also occur as a result of the hypovolemic shock of surgery or trauma. To develop an appropriate rationale for fluid therapy in high-risk surgical patients, the relationship between fluid balance, hemodynamics, the onset of ARDS by physiologic criteria (shunt greater than or equal to 20%, and/or PaO2/FiO2 ratio less than 250) and the onset of pulmonary infiltration (PI) associated with ARDS were examined. Fifty patients were prospectively followed from admission throughout their hospitalizations; 38 (76%) had trauma and 12 (24%) were postoperative. Cardiac index, central venous pressure (CVP), wedge pressure (WP), and shunt (Qsp) were measured. All chest x rays were read by one staff radiologist who was blinded to the patients' identities. PI was graded from "0" to "4" (0 = no PI, 4 = maximum PI). The first x ray reading of "2" or greater was used as the time of onset of PI. ARDS by physiologic criteria occurred in 29 of 50 (58%) patients; 27 of these 29 (94%) also developed +2 or greater PI. The mean onset times of ARDS and of +2 PI were 40 +/- 41 hours and 40 +/- 38 hours, respectively. The ARDS patients had a significantly smaller net positive fluid balance than the non-ARDS patients over the first 40 hours after admission (+6,831 ml +/- 4,909 ml vs 12,440 ml +/- 7,817 ml, (P less than 0.01)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of Dolichos biflorus lectin and other lectin-horseradish peroxidase conjugates in staining of cutaneous blood vessels in the hairless mini-pig.

Angiogenesis is necessary for normal growth, wound healing, and plays a key role in many pathologic processes. A variety of endothelial markers have been used to investigate angiogenesis. Unfortunately, excellent markers for vascular endothelium in human tissues exhibit little or no staining of endothelia in tissues of other animal species, including the pig. We are interested in the hairless Yucatan strain of mini-pig as an animal model for studying cutaneous wound healing because its skin is histologically and functionally very similar to that of man. Hoping to find a specific marker to identify vascular endothelium in the mini-pig, we therefore screened a battery of 11 different lectin-horseradish peroxidase conjugates. Based on specificity and staining intensity, Dolichos biflorus agglutinin (DBA) was chosen from this battery to investigate vascular changes in the healing of cutaneous wounds in the mini-pig. When compared with routine histologic sections stained with hematoxylin and eosin, blood vessels were much easier to identify in sections stained histochemically with DBA. Lectin histochemistry was particularly useful in investigations of early events in angiogenesis during wound healing when newly derived capillary buds and minute blood vessels were obscured in normal histologic sections by an inflammatory cell infiltrate associated with the healing wound. Ultrastructural lectin cytochemistry revealed staining along the luminal surface and the basolateral plasmalemma of endothelial cells. Histochemical staining with DBA promises to provide a useful method for further investigation of angiogenesis and other vascular phenomena in a variety of normal and pathologic processes using the hairless Yucatan strain of mini-pig as the animal model.

Animals↗

Delayed healing in full-thickness wounds treated with aluminum chloride solution. A histologic study with evaporimetry correlation.

Optimizing wound healing parameters seems to be the utmost importance in the present age of sophisticated wound care and dressings. We studied the effect of two hemostatics: 30% aluminum chloride and ferric subsulfate (Monsel's solution) on the rate of wound healing in Yucatan miniature hairless pigs. Wound healing was examined in occluded and nonoccluded full-thickness 3-mm punch biopsy wounds. Wounds were treated either with 30% aluminum chloride solution or ferric subsulfate solution or were allowed to clot with minimal pressure from a gauze pad. The course of wound healing was followed utilizing evaporimetry readings from the wound sites in addition to periodic histologic examination in an attempt to correlate the evaporimetry readings with corresponding histology. Delay in reepithelialization was noted histologically both in wounds treated with aluminum chloride and in those treated with ferric subsulfate compared to controls. Presumably this delay was the result of tissue necrosis caused by these hemostatic agents, resulting in slightly larger and less cosmetically acceptable scars. Plots of evaporimetry data revealed a biphasic pattern of water loss during healing, with an initial rapid decline in water loss followed by a much slower decline. Histologic reepithelialization seemed to correlate best with the point on the evaporimery curve where the slope changed from the phase of rapid water loss to a slower rate.

Aluminum↗

Degradation of porcine dermal connective tissue by collagenase and hyaluronidase.

Selective destruction of connective tissue may be a useful therapeutic tool in conditions associated with abnormal deposition of scar tissue. We have investigated intradermal injections of clostridial collagenase and bovine testicular hyaluronidase alone and in combination in Yucatan miniature hairless pigs. Collagenase in combination with hyaluronidase was quite efficient at destroying the connective tissue matrix, although elastic tissue appeared to be completely spared. Collagenase alone at higher doses degraded collagen, but hyaluronidase had little effect on connective tissue architecture.

Animals↗

Controlled comparison of plasma and serum for cystic fibrosis protein.

Investigators who have previously reported attempts to utilize the isoelectric focusing (IEF) method to detect the cystic fibrosis protein (CFP) in blood samples from CF homozygotes and heterozygotes, and normal healthy controls have restricted their evaluations to serum samples. The requirement of using serum and the stringent conditions laid down for the collection, processing, and storage of serum samples have been impediments, however, to the successful use of the IEF method for CFP detection. We now report results obtained from controlled ("blind") comparative analyses of matched serum and plasma samples from CF homozygotes and heterozygotes, and normal healthy controls which indicate that the CFP is present in plasma and that heparinized plasma in particular may be a better fluid than serum for use in future studies on the CFP.

Blood Protein Electrophoresis↗

A method to test large numbers of bovine semen samples for viral contamination and results of a study using this method.

A procedure to test large numbers of semen samples for viral contamination is described. The procedure has the advantages of being simple to perform, sensitive and a relatively inexpensive method to test pooled semen samples, but it has the disadvantage of requiring serologically negative calves and sheep, isolation facilities to prevent environmental contamination during the testing procedure and relatively long times to obtain results. Using this in vivo procedure called the "Cornell Semen Test", it was found that of 40,000 ejaculates tested during a four year period none contained Infectious Bovine Rhinotracheitis Virus, Bovine Herpes Mammalitis Virus, Bovine Leukemia Virus nor Bluetongue Virus at infectious levels. The only virus that was found in a limited number of pools of semen was Bovine Virus Diarrhea Virus. It is recommended that if large volumes of pooled semen are to be tested for viral contamination that this procedure be used.

Journal Article↗