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Biomedical subjects

D L Dyess

Publications and source records attributed to D L Dyess.

At least 19 recordsLinked to original sources

Attenuation of histamine-induced endothelial permeability responses after pacing-induced heart failure: role for endogenous catecholamines.

OBJECTIVE: After congestive heart failure (CHF), lung endothelial permeability responses to a number of perturbations, including acute barotrauma, angiotensin II, and thapsigargin are blunted. Our hypothesis was that similar attenuation of permeability responses occurs in peripheral vascular beds after CHF. We compared peripheral microvascular permeability responses to the autacoid histamine in control dogs and in dogs paced to heart failure (245 bpm for approximately 36 days). Since catecholamines attenuate autacoid-induced increases in microvascular permeability in skin and muscle in normal animals, we also tested whether the known elevation in catecholamines in CHF was involved in any downregulation of permeability responses in this group. METHODS: Control and paced dogs were anesthetized, intubated, and ventilated, and a hindpaw lymphatic cannulated. The reflection coefficient for total proteins (sigma) was measured at baseline and during one-hour, local intra-arterial histamine infusion. RESULTS: In controls, sigma fell from 0.83 +/- 0.02 to 0.73 +/- 0.04 after histamine (p < 0.05), while in the paced group sigma was no different from that at baseline (0.77 +/- 0.02). To test whether this difference was due to endogenous catecholamines, dogs were pretreated with propranolol (controls only) or the specific beta 2-antagonist ICI 118,551 prior to histamine infusion. After beta-blockade, histamine significantly reduced sigma in both control (0.83 +/- 0.01 to 0.55 +/- 0.05) and paced (0.83 +/- 0.01 to 0.57 +/- 0.07) groups (p < 0.05). CONCLUSION: We conclude that endogenous catecholamines, acting via beta 2-adrenergic receptors, attenuate the permeability response to histamine in pacing-induced heart failure.

Adrenergic beta-Antagonists↗

Human breast carcinoma patients develop clonable oncofetal antigen-specific effector and regulatory T lymphocytes.

Oncofetal Ag (OFA) is a 44-kDa glycoprotein expressed during early to mid-gestation fetal development and re-expressed as a surface Ag by tumor cells soon after transformation. The Ag is detectable on all types of human and rodent tumors tested, but is undetectable on normal cells. In experimental animals it is autoimmunogenic and induces potentially protective T cell responses both after experimental immunization and during tumor development subsequent to carcinogenic insult. To determine whether this tumor-associated Ag is also immunogenic for human T lymphocytes, breast carcinoma patients' peripheral blood mononuclear leucocytes were stimulated in vitro with autologous tumor cells in the presence of IL-2, gamma-IFN, and IL-6 for 2 wk. The tumor-reactive cells were then restimulated and cloned by limiting dilution, and the clones were analyzed. We established 24, 19, 11, and 16 tumor-reactive clones from the four respective patients. Of those, 4, 6, 4, and 7, respectively, proliferated specifically to purified OFA. Both CD4 and CD8 OFA-specific clones were established, which responded equally well to purified OFA or 32- to 44-kDa immature laminin receptor protein. All were CD3+, TCR-alpha beta+. All CD4 clones secreted gamma-IFN, but neither secreted IL-4 nor IL-10. Both IFN-gamma-secreting cytotoxic CD8 clones and IL-10-secreting inhibitory CD8 clones were established. Thus, during human cancer development, the same types of OFA-specific effector and regulatory T cells are induced as during murine T lymphomagenesis.

Adult↗

Regional blood flow response to hypothermia in premature, newborn, and neonatal piglets.

BACKGROUND/PURPOSE: Hypothermia (HT) remains a significant stress to the newborn and has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). The authors assessed the effect of transient HT (32 degrees C) on regional organ blood flow in anesthetized piglets at age 7 to 10 days preterm (PREM), 1 to 2 days (NB), and 1 to 2 weeks (NEO). METHODS: Radiolabeled microspheres were used to determine organ blood flows (mL/min/g) at baseline, 15, and 60 minutes after HT and 60 minutes after rewarming to baseline core temperature. RESULTS: Heart rate and cardiac output decreased significantly in all groups. Cardiac flow decreased significantly in the NEO group, and central nervous system (CNS) flow decreased significantly in the NB and NEO groups. Both returned to baseline levels after rewarming. The PREM group experienced decreased cardiac, CNS, and intestinal blood flows but not to significant levels. NB and NEO intestinal blood flow showed significant decreases, which remained so after rewarming (a response not seen in hypoxia or hypovolemia). Cardiac output did not return to baseline levels in any group. CONCLUSIONS: HT causes derangements in organ blood flows that differ from other deleterious stimuli such as hypoxia and hypovolemia. The prolonged intestinal ischemia supports HT as a factor in the development of NEC. This delay may offer opportunity to intervene in an attempt to lessen ischemia-reperfusion injury.

Age Factors↗

Dynamic magnetic resonance imaging in evaluating suspicious breast lesions: correlation with pathologic findings.

BACKGROUND: We used dynamic magnetic resonance imaging (MRI) to study breast lesions in 13 women. METHODS: We observed differences in contrast uptake between benignancy and malignancy in 14 suspicious breast lesions. Three-dimensional (3D) gradient echo sequences were obtained before and after administration of gadolinium-based contrast medium (0.16 mmol/kg). The percentage of signal increase in lesions was measured in a series of five 90-second sequences, and time-enhancement patterns were correlated with pathologic diagnoses. RESULTS: Seven benign lesions and three breast cancer recurrences showed less than 185% signal increase at 90 seconds after contrast administration. Three new breast cancers and one recently biopsied benign lesion showed more than 185% signal increase at 90 seconds. CONCLUSION: Using this MRI technique, we can discriminate between new breast cancers (more than 185% early signal increase) and breast cancer recurrence and/or benign lesions (less than 185% early signal increase) but cannot distinguish recurrent from benign lesions.

Breast↗

Regional blood flow redistribution in preterm piglets with hemorrhage and resuscitation.

Acute hemorrhage in premature infants occurs as the result of obstetrical complications, birth trauma, or operative procedures. This study evaluates the response of the preterm piglet to acute hemorrhage and resuscitation. Piglets delivered by Caesarean section 7-14 days preterm underwent acute arterial/venous hemorrhage (20 cc/kg). At 0, 15, and 60 min after hemorrhage, hemodynamic parameters and regional blood flows (reference organ technique) were measured. Animals were then resuscitated with shed blood (20 cc/kg), crystalloid (60 cc/kg), or colloid (dextran 40, 20 cc/kg) with study parameters obtained 30 min later (statistical analysis by ANOVA). Significant decreases in blood pressure (BP) and cardiac output (CO) occurred after hemorrhage. BP and CO were reestablished to near control levels following resuscitation with blood and crystalloid. Dextran failed to return BP to baseline; however, it resulted in CO 1.7 x control. Heart and CNS blood flow were not significantly influenced by hemorrhage; however, dextran increased flows to these organs significantly above control levels. In the kidney and small bowel, flows decreased significantly following hemorrhage; blood and crystalloid restored flows to near baseline, while dextran resulted in flows significantly greater. In summary, the preterm piglet responds to hemorrhage with maintenance of blood flow to the heart and brain and significantly decreased flows to the kidney and small intestine. Flows following resuscitation with blood and crystalloid are comparable to those in control. Dextran resuscitation resulted in flows significantly greater than baseline; this response might be detrimental with ongoing hemorrhage and/or prolonged ischemia.

Animals↗

Effects of dopamine and dobutamine on regional blood flow distribution in the neonatal piglet.

OBJECTIVE: The authors determined the effects of dopamine and dobutamine on organ blood flow in newborn piglets. SUMMARY BACKGROUND DATA: Although the hemodynamic effects of dopamine and dobutamine are well described in adults, little is known of their consequences in neonates, and their impact on organ perfusion in premature infants is unclear. METHODS: Cannulae were placed in the femoral vessels and left atrium of term (1-14 days old) and prematurely delivered (Ceasarean section at 90% of term gestation) piglets. After stabilization, radiolabeled microspheres were injected. A continuous infusion of dopamine or dobutamine was started, and other microspheres were injected at 5, 10, and 15-micrograms/kg/minute drug doses (allowing a 20-minute equilibration period at and between each dose). Blood flows (mL/minute/g tissue) to organs were determined using reference organ techniques. RESULTS: In term animals only, dobutamine and dopamine increased systemic mean arterial pressure at the 15-micrograms dose. In term piglets, dobutamine produced dose-dependent increases (p < 0.05, analysis of variance) in heart and brain blood flow, although small intestinal blood flow decreased (1.47 +/- 0.13 mL/minute/g baseline to 1.31 +/- 0.11 mL/minute/g at 15-micrograms dose). There were no significant changes in blood flow to these organs in preterm animals. Dopamine significantly (p < 0.05) increased heart blood flow in both groups. Dopamine also increased small intestinal blood flow in term (1.63 +/- 0.22 mL/minute/g baseline to 3.13 +/- 0.34 mL/minute/g at 15-micrograms dose) and premature (0.31 +/- 0.10 mL/minute/g baseline to 1.11 +/- 0.29 at 15 micrograms dose) piglets. CONCLUSIONS: Dopamine may prove a valuable adjunct when a premature infant is at risk for conditions that reduce alimentary tract blood flow.

Animals↗

Effects of graded thermal injury on microvascular permeability at the site of injury.

To define whether capillary permeability traits at the site of a burn differ according to injury severity, a canine hind leg lymphatic was cannulated to measure macromolecular permeability in response to three different scalding solutions. Leg venous pressure was raised to approximately 40 mm Hg and maintained until a minimal lymph-to-plasma total protein ratio (CL/CP)min and steady-state lymph flow (QL; microliter/min/100 g) was attained. The protein reflection coefficient (1-CL/CP), fluid filtration coefficient (Kf; microliter/min/mm Hg/100 g), and QL were determined before and for 6 hr after a 5-sec hind paw immersion in either 100 degrees C (n = 7), 80 degrees C (n = 7), or 70 degrees C (n = 7) water. A group of five animals served as controls. In the absence of any systemic hemodynamic alterations, the 100 and 80 degrees C scald groups experienced significant (P < 0.05, ANOVA) increases in QL, CL/CP, and Kf as compared to respective preburn values and time-matched unburned control values. Most monitored parameters were significantly higher following 100 degrees C injury vs 80 degrees C injury. Parameters in the 70 degrees C group did change after scald, but were not significantly different from preburn values or from the control group. Alterations in capillary permeability to protein and fluid flux measured at the burn site are graded, not all or none phenomena, being dependent upon the severity of injury.

Analysis of Variance↗

Redistribution of organ blood flow after hemorrhage and resuscitation in full-term piglets.

Newborn piglets (aged 1 to 2 days and 7 to 14 days) were used to study (1) the redistribution of organ blood flow after a 25% acute blood loss and (2) the response to resuscitation with shed blood (20 mL/kg), crystalloid (normal saline [NS] or lactated Ringer's [LR]; 60 mL/kg), and colloid (Dextran-40, 20 mL/kg). Hemodynamic parameters showed little differences in the response to hemorrhage and resuscitation. The two age groups had no significant differences in parameters or blood flow (results combined). The animals maintained flow to the heart and central nervous system (CNS) and had significantly decreased flow to the kidneys and splanchnic organs. In the gastrointestinal tract, the small intestine was affected most severely, with a significant decrease in blood flow, especially to the mucosa. In all organ systems, Dextran 40 restored blood flow to levels significantly above the baseline. Shed blood and crystalloid restored flow to organs sustaining decreased flow, but crystalloid did not restore flow to the baseline level in the kidney and all segments of the gastrointestinal tract.

Animals↗

The effects of albumin administration on microvascular permeability at the site of burn injury.

In a canine hind leg model, lymph flow (QL), lymph (CL), and plasma (CP) total protein concentrations, the reflection coefficient for total proteins (sigma d), and the filtration coefficient (Kf) were determined before and for 6 hours after a 5-second 100 degrees C hind paw scald (3% total body surface area, TBSA). Before injury, hind leg venous pressure was elevated and maintained by outflow restriction until a minimal, steady-state CL/CP ratio was achieved. Albumin (5%) was infused 30 minutes after the scald at low (0.4 mL/kg/% TBSA) or high (2 mL/kg/% TBSA) doses. Scald uniformly increased QL, CL/CP, Kf, and paw weight gain (PWG). Whereas postburn infusion of low-dose albumin mildly attenuated increases in CL/CP and PWG noted in scald-alone animals, no differences were noted between the scald and scald/high-dose albumin groups.

Albumins↗

Effects of pentafraction administration on microvascular permeability alterations induced by graded thermal injury.

BACKGROUND: Pentafraction is a pentastarch derivative hypothesized to limit burn edema by "sealing" damaged capillaries, restoring a barrier to fluid translocation and macromolecular (protein) flux. METHODS: Canine hind paw lymph flow (QL) and lymph (CL) and plasma (CP) protein concentrations were measured before and for 6 hours after (1) 5-second 100 degrees C (n = 6) or 80 degrees C (n = 6) foot paw scald, (2) 100 degrees C (n = 5) or 80 degrees C (n = 5) foot paw scald followed 30 minutes later by a 4 cc/kg bolus of 6% pentafraction, or (3) pentafraction infusion without scald (n = 5). Before scald or pentafraction infusion, hind paw venous pressure was elevated and maintained by outflow restriction until a steady state, minimal CL/CP was reached. The reflection coefficient, sigma d, was determined as 1-CL/CP, and the (fluid) filtration coefficient (Kf) was calculated. RESULTS: Scalding uniformly produced statistical (p < 0.05, ANOVA) increases in QL, CL/CP, sigma d, Kf, and paw weight gain. Postburn pentafraction infusion produced no enduring alterations in any measured parameter as compared with those of animals who received a matched severity scald without pentafraction. CONCLUSIONS: Pentafraction does not appreciably ameliorate the adverse microcirculatory consequences observed at the site of burn injury.

Animals↗

Indomethacin-induced blood flow distribution in premature and full-term piglets.

Indomethacin (IND), widely used in premature infants to effect nonoperative closure of patent ductus arteriosus (PDA), has been implicated in gastrointestinal tract (GI) perforations and necrotizing enterocolitis (NEC). The vasoactive effects of IND could simultaneously affect regional blood flow distribution, specifically a decrease in intestinal blood flow. This study determined blood pressure (BP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and regional blood flows (mL/min/g) at baseline, 15, 60, and 120 minutes after intravenous infusion of IND (0.4 mg/kg) in three groups: preterm piglets delivered 7 to 10 days before term; 1- to 2-day-old piglets; and 7- to 14-day-old piglets. IND did not significantly affect hemodynamic parameters (BP, HR, CO, TPR) or regional blood flows to the heart, central nervous system, kidney or GI tract in the premature animals. In 1- to 2-day-old animals, a significant increase in BP and TPR occurred at 120 minutes, with significant decreases in blood flow to the GI tract in the esophagus, stomach, and rectosigmoid. In the 7- to 14-day group CO significantly decreased while TPR increased. Significant decreases in blood flow occurred throughout the GI tract, most pronounced in the small intestine and colon, essentially due to decreased mucosal blood flow. Our study indicates that indomethacin can cause selective GI tract mucosal ischemia, and that the effect is increased in the more developed animal. This effect on mucosal blood flow suggests the GI tract disturbances seen after IND administration are due to an ischemic injury to mucosa previously affected by ischemia-reperfusion injury from other stresses.

Aging↗

Effects of hypertonic saline and dextran 70 resuscitation on microvascular permeability after burn.

Administration of hyperosmolar fluids to burn patients has been proposed as a means of decreasing resuscitative fluid volume and, subsequently, wound edema accumulation. To test this hypothesis, canine hindpaw lymph flow (QL) and lymph (CL) and plasma (CP) total protein concentrations were measured, and capillary filtration coefficient (Kf) was calculated before and for 6 h after a 5-s 100 degrees C footpaw scald. Scald was followed 30 min later by bolus infusion (4 ml/kg) of 7% saline or 6% Dextran 70 or the two in combination. Before scald, venous pressure was elevated until a minimal CL/CP was reached. The reflection coefficient (sigma d) was calculated by the formula: 1-minimal CL/CP. Scald increased QL, CL/CP, and Kf, but sigma d was decreased (P less than 0.05). Compared with burn alone, 7% saline exacerbated burn-induced increases in QL and Kf. In contrast, infusion of Dextran 70 did not exacerbate these changes in QL or Kf. Perhaps more importantly, Dextran 70 may have attenuated the increase in CL/CP and reduced edema formation in the burned hindpaw. However, the addition of 7% saline to the dextran eliminated these beneficial effects.

Animals↗

Selective nonoperative management of solid breast masses.

A prospective study evaluated the hypothesis that, following consistent clinical and mammographic guidelines, many women with breast masses can be nonoperatively managed. One hundred eighty women with solid breast masses were assigned both a clinical and mammographic diagnosis by each a surgeon and radiologist. Immediate biopsy (n = 78) was recommended when either clinician thought that the mass was malignant (52 cancers). The remainder were offered a trial of observation, with interval biopsy performed upon patient preference or for increased clinical/mammographic concern. Of the 89 who consented to this, 70 received long-term follow-up (X = 22 months) with improvement in the characteristics of the mass. The diagnosis of invasive cancer was delayed in two women initially observed, with no apparent impact on survival. It is concluded that many women with solid breast masses can be safely observed. Biopsy remains warranted for any mass suspicious for malignancy on clinical/mammographic grounds, or if follow-up cannot be assured.

Biopsy↗

Increased hyaluronan flux from skin following burn injury.

Hyaluronan (formerly hyaluronic acid) is an important constituent of the interstitial matrix in skin. Following major burn injury in animal models, plasma hyaluronan can increase to levels 10-fold greater than normal. The present experiments were designed to determine whether this is a result of the increased lymph flow (QL) accompanying the injury or of an increased release of hyaluronan from the burned skin and subcutaneous tissue. The lateral saphenous vein and a prenodal lymphatic were cannulated in the hindpaw of five anesthetized canines. Hindpaw venous pressure was elevated until the total protein concentration in lymph declined to steady-state levels, and QL and hyaluronan flux (QL X [hyaluronan]) was measured. A minor burn was inflicted by immersion of the paw into 100 degrees C water for five sec, and measurements were repeated at regular intervals for a minimum of 4 hr. Burn injury resulted in significant and persistent increases in QL (154 +/- 61 microliters/min versus 562 +/- 105 microliters/min 4 hr postburn) and lymph total protein concentration (1.34 +/- 0.04 g/dl versus 4.08 +/- 0.18 g/dl 4 hr postburn), while lymph hyaluronan concentration fell (3.01 +/- 0.20 micrograms/ml versus 2.1 +/- 0.16 micrograms/ml 4 hr postburn). The resultant increase in hyaluronan flux (0.42 +/- 0.13 microgram/min versus 1.17 +/- 0.22 microgram/min 4 hr postburn) appears to be a function of lymph flow rather than burn-induced release of skin hyaluronan. Hence, the increased plasma concentration of hyaluronan following major burns is likely a consequence of increased lymph flow from the site of injury.

Animals↗

Intraoperative evaluation of intestinal ischemia: a comparison of methods.

Methods for evaluating intestinal ischemia include standard clinical criteria, Doppler ultrasonography, and intravenous fluorescein injection. Each has disadvantages, and a combination of methods is often used. The purpose of this study was to determine whether surface oximetry could be used to assess perfusion in an animal whose intestinal diameter approximates that of infants. Reversible arterial, venous, and arteriovenous occlusion was studied in rabbit intestines. After 6 to 8 hours of occlusion, intestinal vascularity was evaluated by the four methods listed. Doppler ultrasonography and surface oximetry were found to be unreliable tools for assessing perfusion in this animal model. We conclude that standard clinical criteria and fluorescein remain the standards for intraoperative evaluation of intestinal perfusion.

Animals↗

Necrotizing enterocolitis in multiple-birth infants.

Over a 5-year period, 20 infants of multiple-gestation births (16 twin, 2 triplet) developed necrotizing enterocolitis (NEC) (15 infants) or suspected NEC (5 infants). During the same period, 532 infants of multiple gestations were admitted to our neonatal intensive care unit, yielding a NEC incidence in this population of 3.8%. In two twin sets, both infants developed NEC or suspected NEC, and in three sets only the affected twin was transferred to our nursery. Five infants required surgical intervention (25%) and three infants died (overall mortality, 15%). Fifteen siblings who did not develop NEC served as a control group. Analysis showed that the 1-minute Apgar score was the most significant factor in predicting NEC (P less than .028) and need for surgical intervention (P less than .020). In this series, 82% of the infants with 1-minute Apgar less than 6 developed NEC, whereas 31% with 1-minute Apgar greater than 6 developed NEC.

Apgar Score↗

A new technique for sutureless intestinal anastomosis. A prospective, randomized, clinical trial.

A polyglycolic acid device has been designed for the performance of sutureless colonic anastomoses. The use of this biofragmentable anastomosis ring (BAR) was compared with conventional techniques in a prospective, randomized study of 59 patients (x age, 49 years) undergoing ileocolostomy (n = 23) or colocolostomy (n = 36). The anastomotic technique was determined at surgery by randomization (BAR, 27 patients; suture, 16 patients; staple, 16 patients). Performance of an anastomosis with the BAR required an average of 22 minutes, a stapled anastomosis required 33 minutes, and the suture technique required 37 minutes. Learning curve error contributed to the six intraoperative complications that occurred with performance of the anastomosis (BAR, three; end-to-end anastomosis [EEA] instrument, three). The two postoperative deaths were unrelated to the anastomosis. Length of hospitalization in uncomplicated patients was the same among the three groups. The 17 patients with prolonged hospitalization had complications unrelated to anastomotic technique. All patients were followed for a minimum of 6 weeks; no additional complications were identified. We concluded that 1) the BAR is a rapid, safe method for performance of sutureless anastomoses; 2) perioperative mortality and morbidity rates of the BAR are comparable to conventional techniques of suture and staple; and 3) long-term follow-up of BAR patients is warranted to determine the incidence of complications, such as structure and/or stenosis.

Anastomosis, Surgical↗