Big and tall: protective against colorectal cancer?
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Adult↗
Biomedical subjects
T A Miller
Publications and source records attributed to T A Miller.
Differing effects of anesthetics on splanchnic arterial blood flow during hemorrhagic shock.
The effect of anesthesia on splanchnic blood flow was examined during hemorrhagic shock and resuscitation. Sprague-Dawley rats were anesthetized with the inhalation anesthetic, methoxyflurane, or pentobarbital (65 mg/kg). Transonic Doppler flow probes were placed around the superior mesenteric artery (SMA) and the abdominal aorta, and the animals were subjected to acute hemorrhage (or sham) to 30 mmHg for 90 min followed by 30 min of resuscitation with shed blood (n = 6/group). At 90, 105, and 120 min, sham animals in both anesthetic groups showed comparable blood pressures with a 50% decrease in SMA and aortic blood flow. Acute hemorrhage decreased SMA blood flow by 94.5 +/- 0.01 and 86.0 +/- 2.8%, respectively, in the pentobarbital and methoxyflurane groups, with similar changes occurring in aortic blood flow. During resuscitation, arterial pressure remained significantly depressed and SMA blood flow decreased by 65% in the pentobarbital group, whereas blood pressure returned to control levels and SMA blood flow increased to 56% of control values (P < 0.001) in the methoxyflurane group. The findings indicate that the choice of anesthetic agent may significantly impact splanchnic blood flow and needs to be taken into account when designing experiments examining effects of hemorrhagic shock.
Anesthetics↗
Esophageal, gastric, and small intestine.
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Esophageal Neoplasms↗
Lipedema: a clinical entity distinct from lymphedema.
In a review of 250 cases of lymphedema of the lower extremity, 9 patients were noted to share unique similarities in their history and physical findings. Although these patients had mild swelling in their pretibial areas and were all referred with a diagnosis of lymphedema of the legs, their findings differed significantly from the usual patient with either congenital or acquired lymphedema. Notably, the lower extremity swelling was always bilateral and symmetrical in nature and never involved the feet. Skin changes characteristic of lymphedema were not found, and consistent fat pads were present anterior to the lateral malleoli in each patient. These findings are representative of a clinical entity known as lipedema, which is distinct from lymphedema and for which treatment may be different.
Adipose Tissue↗
In vitro translation of diapause mRNA from the fat body of active and diapause larvae of the pink bollworm, Pectinophora gossypiella (Saunders).
A diapause associated protein (DAP) (M(r) 103,000) was isolated from the hemolymph and fat body of diapausing fourth instar larvae of the pink bollworm Pectinophora gossypiella. The protein has been named Pectinophora diapause protein (PDP). The in vitro translation peptide patterns of total RNA from the fat body of actively feeding fourth instar, wandering, prediapause, early diapause, mid-diapause, and late diapause larvae in rabbit reticulocyte lysates showed the presence of poly (A)+ RNA sequence of PDP. The antigen was immunoprecipitated by polyclonal antiserum. It was concluded that the transcription of the PDP gene in the fat body cells started in the late fourth instar larva and that the expression of this gene was regulated at the level of transcription in the fat body of diapausing larvae. Northern hybridization analysis revealed that wandering fourth instar larvae (diapause individuals) maintain a relatively low level of diapause message (mRNA/2.4 kb) in their fat body cells which may be necessary for the induction of diapause.
Animals↗
Adverse effects of vagotomy on ethanol-induced gastric injury in the rat. Absence of a role for glutathione redox cycle.
Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6-8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Alterations in rat intestinal transit by morphine promote bacterial translocation.
Translocation of enteric microorganisms from the intestinal tract to extraintestinal sites has been proposed as an early step in the development of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial translocation using morphine as a pharmacologic inhibitor of such transit. In the first experiment, either normal saline (N = 8) or morphine sulfate (20 mg/kg; N = 8) was injected subcutaneously. Two hours later, morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this regimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) were injected intraduodenally in each group. The bowel was removed 25 min later, divided into 5-cm segments, and the content of dextrans measured. Small bowel propulsion was expressed as the geometric center of the distribution of dextrans throughout the intestine (in percentage length of small bowel). Gut propulsion was significantly reduced after morphine treatment as compared to controls (32.8 +/- 8.2% vs. 55.8 +/- 4.0%; P < 0.01). In 16 additional rats, saline or morphine was again administered as described. After 24 hr, samples were obtained from the mesenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, jejunum, ileum, and cecum for standard bacteriology. The bacterial counts increased significantly in each intestinal segment following morphine treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Dietary risk factors and colorectal polyps: apparently gender does make a difference.
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Adenoma↗
Leiomyosarcoma: not all gastric malignancies have a dismal prognosis.
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Humans↗
Effect of total parenteral nutrition plus morphine on bacterial translocation in rats.
OBJECTIVE: This study tested the hypothesis that gut stasis induced by parenteral morphine sulfate (MS) leads to enhanced bacterial translocation in rats on total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: TPN and MS are common adjuncts in the care of critically ill patients. TPN is known to provoke a variable degree of translocation. MS induces gut stasis with an accompanying bacterial overgrowth. The effect of these two treatments in combination on translocation is not known. METHODS: Rats were provided with central and subcutaneous lines for the continuous infusion of nutrients and drugs, respectively. Intestinal transit was assessed by the caudal movement of a fluorescent marker intubated into the proximal duodenum. Quantitative bacteriology was carried out from various segments of the gut and from ileocecal mesenteric lymph nodes (MLN), spleen, liver, and systemic blood obtained by cardia puncture on sacrifice at 96 hours. RESULTS: Transit was unchanged by TPN alone but prolonged when given in combination with MS. Bacterial overgrowth was also enhanced by MS and increased the bacterial translocation to MLN from 50% of animals with TPN, to 100% in those receiving both TPN and MS; the colony-forming units per MLN increased from 33 +/- 14 with TPN alone to 2079 +/- 811 (STD) with TPN plus MS. Furthermore, no bacteria were found at systemic sites with TPN alone, but in 93.3% of animals receiving TPN and MS. In a subgroup of rates provided with glutamine in TPN, the TPN plus MS effects on translocation were not reversed. CONCLUSIONS: These observations demonstrate the important role that morphine plays in promoting translocation, presumably by disrupting fasting motility and enhancing bacterial overgrowth.
Animals↗
Protective action of oral N-acetylcysteine against gastric injury: role of hypertonic sodium.
N-acetylcysteine (NAC), when administered orally as a 20% solution, is a potent protective agent against gastric injury in the rat stomach induced by absolute ethanol. The present study was undertaken to define the means by which this protection is mediated. The notion that NAC acts as a glutathione precursor was excluded when N-acetylserine (NAS) was noted to be equally protective against alcohol injury. The NAS molecule contains a hydroxyl moiety at the site where NAC contains a sulfhydryl. To orally administer 20% NAC at a neutral pH, NaOH is added to the free acid form to keep NAC in solution. We determined by titration that a sodium concentration of 1.2 M results. Thus it became apparent that the protective effect of NAC might be mediated through the sodium employed to titrate NAC. Accordingly, we examined various sodium salts and assessed their relative protective effects against alcohol injury. Both sodium acetate and sodium chloride in 1 M solutions were found to be equally effective in preventing alcohol injury with the same efficiency as 1 M sodium solutions of NAC and NAS, excluding the acetate portion of NAC and NAS as being of primary importance for protection to occur. Further study, using different concentrations of sodium chloride (i.e., 150-1,000 mM) revealed that the 1 M solution was most optimal in preventing alcohol injury. One molar sodium by itself and when administered as part of the NAC solution also prevented gastric injury by concentrated acid and base.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcysteine↗
Gastric damage caused by acidified ethanol: role of molecular HCl.
This study was undertaken to test the hypothesis that an increase in the concentration of molecular HCl in ethanolic solutions is at least partly responsible for the severity of damage seen with acidified ethanol. To accomplish this goal, we studied the synergistic relationship of HCl and ethanol by holding ethanol constant at 50% (vol/vol) and varying the acid concentration. In another experiment, acid concentration was held constant at 150 mM HCl, and the percentage of ethanol was varied. Our hypothesis was also tested by substituting sulfate for chloride to form H2SO4, a nonpermeant molecular acid. Results of our studies clearly showed that substitution of sulfate for chloride greatly reduced gastric damage, supporting the hypothesis that diffusion of molecular HCl is contributing to the damage by acidifying cells. In all cases, acidified ethanol solutions using HCl were more damaging than the individual components alone, and the severity of the damage caused by 50% ethanol was noted to be dependent on the concentration of HCl. We therefore conclude that the severity of acidified ethanol damage is dependent on cellular acidification caused by diffusion of molecular HCl.
Animals↗
Reevaluation of the linkage between acute hemorrhagic shock and bacterial translocation in the rat.
The present study was undertaken to determine the conditions under which acute periods of hemorrhagic shock induce bacterial translocation. Rats (at least six per group) were anesthetized intraperitoneally with the barbiturate, pentobarbital (50 or 65 mg/kg), or the inhalation anesthetic methoxyflurane. Following anesthesia, the femoral artery was catheterized, from which blood was withdrawn to maintain a mean arterial blood pressure of 30 mmHg for 30, 60, or 90 min, followed by reinfusion of shed blood. Instrumented, but nonshocked animals served as controls. Rats were sacrificed at 0, 2, or 24 hr postshock, and quantitative bacterial cultures of the mesenteric lymph node complex (MLN), liver, and spleen were made. Within groups, the effects of heparinization were also determined. In pentobarbital-treated animals, regardless of the extent of heparinization, consistent translocation to both MLN and distant organs occurred when shock was prolonged for 90 min, and assessment of translocation was made 24 hr after reinfusion of shed blood. Furthermore, a mortality rate of approximately 30% was found in rats subjected to this protocol. The magnitude of translocation was less consistent, and did not differ from that in sham shock controls, under other conditions of shock and evaluation. In rats anesthetized with methoxyflurane, no mortality occurred, and no statistical significance between the incidence or degree of translocation in shocked animals vs. sham shock controls could be demonstrated, regardless of the shock protocol. In additional studies, effects of these anesthetics on intestinal morphology and superior mesenteric arterial (SMA) flow in the context of hemorrhagic shock were assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia↗
Enhanced healing of large cranial defects by an osteoinductive protein in rabbits.
Two experimental bone-graft substitutes, one composed of a porous hydroxyapatite plus an osteoinductive protein and the other composed of lactomer beads (copolymers of polylactic acid and polyglycolic acid) plus an osteoinductive protein, were evaluated as a means of reconstructing a large cranial defect model created in the rabbit. Twenty-five rabbits underwent a 16 x 20 x 1.5 mm full-thickness (extradural) excision of the parietal bone, were divided into different groups of five rabbits each, and were reconstructed by (1) hydroxyapatite, (2) hydroxyapatite plus protein, (3) lactomer beads, and (4) lactomer beads plus protein, and (5) one group consisted of nonreconstructed controls. The implants were harvested at 12 weeks and analyzed for percentage of bone ingrowth by histologic examination of decalcified mid-coronal sections stained with hematoxylin and eosin. The groups reconstructed with protein-treated implants demonstrated significantly greater amounts of ingrowth than those with untreated implants. Both protein-treated hydroxyapatite and lactomer bead groups had more than twice the amount of bone ingrowth than their respective untreated groups (29.0 versus 12.8 percent, p < 0.005, and 27.0 versus 10.0 percent, p < 0.001, respectively). The new bone found in the protein-treated and untreated implants was quite different: lamellar and woven, respectively. The results strongly suggest a clinical role for the combination of the mechanisms of osteoconduction and osteoinduction in the treatment of bone defects.
Animals↗
A diapause associated protein of the pink bollworm Pectinophora gossypiella Saunders.
A diapause associated protein was electrophoretically isolated from the hemolymph of diapausing last instar larvae of the pink bollworm Pectinophora gossypiella. This protein (M(r) approximately 490,000, glycolipoprotein) was given the name Pectinophora diapause protein (PDP). It is composed of one subunit (M(r) 103,000). The concentration of PDP increased dramatically in the hemolymph of diapausing larvae from 17.4% in prediapause (PD) phase to 29.2% in early diapause (ED) phase reaching a level of 38.6% in larval hemolymph of middiapause (MD) phase. The concentrations of total proteins in the hemolymph of active feeding (A), PD, ED, and MD larvae were 69.8, 106,6, 113.3, and 118 mg/ml, respectively, while those in the fat body of the same larvae were 7.1, 7.4, 8.8, and 4.5 mg/g, respectively. In Pectinophora a drop in the concentration of fat body proteins coincided with a corresponding increase in hemolymph proteins, which suggests an active release of protein from the fat body into the hemolymph during the development of diapause. A partial amino acid sequence of pectinophorin showed the first 15 amino acids starting from the amino terminus of the peptide chain: N-ALA-LYS-THR-ILEU-VAL-GLU-ASN-MET-PRO-PRO-THR-PRO-LEU-ASN-ALA-C.
Amino Acid Sequence↗
Abnormalities in ureter and kidney development in mice given acetazolamide-amiloride or dimethadione (DMO) during embryogenesis.
These experiments more accurately define the effects of the combination acetazolamide-amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide-amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a restricted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown.
Abnormalities, Drug-Induced↗
Protective effect of dimethylthiourea against mucosal injury in rat stomach. Implications for hydroxyl radical mechanism.
The present study was undertaken to determine whether dimethylthiourea (DMTU), a hydroxyl radical scavenger, could prevent gastric injury in the rat stomach induced by various noxious agents. Fasted rats (N = 6-8/group) were given a 1-ml oral bolus of saline or DMTU over the dose range 10-500 mg/kg. After 30 min, animals received 1 ml of 100% ethanol orally and were sacrificed 5 min later. At sacrifice, stomachs were harvested and the degree of macroscopic damage was assessed by planimetry. In selected animals, specimens of gastric mucosa were also processed for histology. Saline pretreatment prior to ethanol exposure resulted in 22.5% injury to the glandular epithelium when assessed macroscopically. DMTU pretreatment prevented such injury in a dose-related fashion with only 2% of the mucosa showing injury with a 500 mg/kg dose (P less than 0.01 vs control). Although the superficial injury involving surface mucous cells induced by ethanol was not altered by DMTU, the deep damage to gastric glands was almost completely prevented. Other experiments in which DMTU was given intraperitoneally demonstrated similar protective effects against ethanol injury. Additional studies showed that indomethacin did not prevent the protective effects of oral or intraperitoneal DMTU, excluding a role for endogenous prostaglandins, and that DMTU was equally protective when administered within minutes or as long as 2 hr prior to ethanol exposure. Furthermore, DMTU was also shown to be protective against gastric injury induced by concentrated acid or base. In in vitro studies in which hydroxyl radicals were actually generated, DMTU was noted to scavenge the hydroxyl radical in a dose-related fashion. The ability of DMTU to prevent gastric injury by three different damaging agents suggests that the hydroxyl radical may play a major role in the pathogenesis of such injury and that DMTU mediated its protective action by scavenging this radical species.
Animals↗
Influence of shock on development of infection during acute pancreatitis in the rat.
This study tested the hypothesis that hypovolemic shock elicits or promotes the development of infection during acute pancreatitis. Pancreatitis was induced in rats by ligation of the common biliopancreatic duct; nonlaparotomized animals served as controls. After 24 hr, the animals were subjected to either sham-shock (instrumented only) or to shock by withdrawal of blood through a femoral artery line by maintaining the mean arterial blood pressure at 30 mm Hg for 1 or 2 hr. After completion of the shock period, the shed blood was returned to the animal. All animals were sacrificed 24 hr later and specimens obtained from portal and systemic blood, liver, spleen, pancreas, and mesenteric lymph nodes for bacteriologic culture using standard techniques. The pancreas was also analyzed by morphometric techniques. The histologic changes of pancreatitis induced by biliopancreatic obstruction were characterized by marked edema with accompanying mild inflammation, hemorrhage, and necrosis. Concomitant with these morphologic findings was an associated translocation of enteric organisms to the mesenteric lymph nodes without spread to distant organs. Shock by itself induced only a mild edema in the pancreas and did not cause bacterial translocation. Furthermore, shock failed to aggravate the morphologic alterations of acute pancreatitis and did not promote bacterial spread to mesenteric nodes over that observed with pancreatitis alone. Thus, we conclude that periods of severe shock lasting up to 2 hr do not play a major role in the pathogenesis of infection in our model of pancreatitis.
Acute Disease↗