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Biomedical subjects

R H Shikes

Publications and source records attributed to R H Shikes.

At least 19 recordsLinked to original sources
PubMed2000

Histologic inflammation in the maternal and fetal compartments in a rabbit model of acute intra-amniotic infection.

OBJECTIVE: This study was undertaken to determine the course of acute inflammation in the maternal and fetal compartments during experimentally induced ascending intra-amniotic infection. STUDY DESIGN: Forty pregnant rabbits at 70% gestation were inoculated endocervically with 10(5) colony-forming units of Escherichia coli. Does were killed at 0, 4, 8, 16, 24, and 30 hours after inoculation. At necropsy, blood, peritoneal fluid, amniotic fluid, and uterine tissue were cultured. Fetal brain, lung, heart, gut, and kidney were collected for histologic examination. Necrosis, infiltrates, congestion, and edema were each assessed semiquantitatively, and mean composite histologic-inflammation scores were compared with analysis of variance. Inflammation, mitotic activity, and apoptosis were evaluated in the fetal brain, and groups were compared with analysis of variance. RESULTS: Twenty-six animals were evaluated after 14 were excluded (lack of fever or positive culture results). A significant increase in histologic inflammation score was seen in the uterus (P<.001), placenta(P = .011), and fetal lung (P = .001) but not in other fetal tissues. These changes were seen earlier in the uterus and placenta and later in the fetal lung. Mitotic activity in the fetal brain decreased significantly by 8 hours after cervical inoculation. There was no inflammation in the fetal brain, and apoptosis in the fetal brain did not increase with time. CONCLUSIONS: Histologic inflammation occurs early in both the uterus and the placenta and later in the fetal lung in the rabbit model of acute intra-amniotic infection. This contrasts with the previously reported chronic model of intra-amniotic infection in the rabbit.

Acute Disease↗
PubMed1996

Hepatic oxidant injury and glutathione depletion during total parenteral nutrition in weanling rats.

Hepatobiliary dysfunction occurs commonly in infants on prolonged parenteral nutrition alimentation; however, the underlying mechanisms causing liver injury are poorly understood. We postulated that oxidant stress played a significant role in parenteral nutrition-induced liver abnormalities and tested this hypothesis in a rat model. Weanling male rats received 8 days of total parenteral nutrition (TPN) through a central venous catheter (TPN group), pair feeding of rat chow and placement of a central venous catheter (sham group), or ad libitum feedings of rat chow (control group). After 8 days of TPN, serum alanine aminotransferase and cholylglycine levels were elevated, hepatocellular steatosis was present, hepatic mitochondria had dilated intracristal spaces, and lipid peroxidation of mitochondria was increased compared with sham and control groups. Hepatic glutathione levels decreased to 16% of control values after 5 days of TPN; this was followed by mitochondrial lipid peroxidation and elevated serum cholylglycine levels after 8 days of TPN. Sham and control rats showed no evidence of mitochondrial lipid peroxidation or liver injury after 8 days. Removal of metabisulfate from TPN solutions and addition of cysteine HCl or choline had no major effect on these findings. Bacterial translocation was not increased in TPN rats. These data suggest that glutathione depletion and oxidant stress are important factors in the pathogenesis of TPN-induced liver abnormalities in the weanling rats.

Animals↗
PubMed1994

Marked reduction in myocardial infarct size due to prolonged infusion of an antioxidant during reperfusion.

BACKGROUND: There has been controversy about whether early reperfusion of myocardial infarcts causes further necrosis mediated by reactive oxygen species or other mechanisms. Unequivocal evidence that therapeutic agents given only during reperfusion can prevent, rather than delay or modify, injury has been sparse. Failure to account for variables, such as collateral blood flow, that influence infarct size independently and attempts to measure infarct size too early in reperfusion may have limited the sensitivity and specificity of some previous studies. METHODS AND RESULTS: After 90 minutes of coronary occlusion and 48 hours of reperfusion in a canine model, we examined the effect on infarct size of intravenous infusion of N-(2-mercaptopropionyl)-glycine (MPG), a diffusible antioxidant. Infarct size and region at risk were measured by post-mortem dual perfusion with triphenyl tetrazolium chloride and Evans blue dyes, and regional myocardial blood flow was measured with radioactive microspheres. Infusion of MPG 100 mg.kg-1.h-1, beginning either 15 minutes before the onset of reperfusion or 30 minutes after the onset of reperfusion and continued until 4 hours of reperfusion and followed by an intramuscular dose, reduced infarct size, normalized for both region at risk and the level of collateral blood flow, by 60% and 45%, respectively. When infusion of MPG was limited to the last 15 minutes of ischemia and the first hour of reperfusion only, the normalized infarct size was reduced by 26%. Heart rate, blood pressure, and their product did not differ among the four groups studied. The plasma half-time of MPG was < 10 minutes. In in vitro experiments MPG was a scavenger of hydrogen peroxide but not of superoxide radical. CONCLUSIONS: After 90 minutes of coronary ligation, infusion of the diffusible hydrogen peroxide scavenger, MPG, for several hours, beginning as late as 30 minutes after the onset of reperfusion, substantially reduced infarct size measured 48 hours later. In this model, necrosis caused by processes during reperfusion may be more extensive than necrosis caused by ischemia alone. Since infusion of this agent for only the first hour of reperfusion was considerably less effective, it appears that most of the oxidant injury leading to necrosis occurred after the first 60 minutes but within the first 4 hours of reperfusion.

Animals↗
PubMed1991

A rabbit model for bacterially induced preterm pregnancy loss: intervention studies with ampicillin-sulbactam.

We conducted experiments with a previously described rabbit model of Escherichia coli-induced preterm pregnancy loss. Does at 70% gestation were inoculated hysteroscopically with 0.2 ml of Escherichia coli (10(5) colony-forming units per milliliter) or saline solution. Animals were randomly assigned to either receive treatment with ampicillin-sulbactam (begun 1 to 2 hours before inoculation and continued for up to 7 days) or to receive no therapy. Animals were killed after delivery or after 7 days. Saline solution-inoculated animals had no pregnancy loss. Of the Escherichia coli-inoculated animals, those treated with ampicillin-sulbactam had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the untreated animals (p less than or equal to 0.001). Cultures from multiple sites, amniotic fluid prostaglandin levels, and maternal progesterone levels were obtained, and the placenta, uterus, and fetal lung were histologically evaluated. In the second phase of the study, the Escherichia coli-inoculated animals were treated with ampicillin-sulbactam at one of three times: at inoculation or 2 or 4 hours after inoculation. The Escherichia coli-inoculated does treated with ampicillin-sulbactam at or before inoculation had significantly fewer deliveries, fewer positive cultures, and more live fetuses than the Escherichia coli-inoculated does in which treatment was delayed 4 hours (p less than or equal to 0.01).

Ampicillin↗
PubMed1991

Reduction of canine myocardial infarct size by a diffusible reactive oxygen metabolite scavenger. Efficacy of dimethylthiourea given at the onset of reperfusion.

A number of scavengers of reactive oxygen metabolites reduce myocardial injury when given before ischemia and reperfusion, but few, if any, have proven to be effective when given near the onset of reperfusion. This is particularly true when infarct size is measured after at least 48 hours of reperfusion, when the full extent of myocardial damage has become apparent. Dimethylthiourea (DMTU) is an extremely diffusible, potent scavenger of hydroxyl radical, hydrogen peroxide, and hypochlorous acid, with a long half-life of 43 hours. Sixteen chloralose-anesthetized dogs underwent 90 minutes of left anterior descending coronary artery (LAD) occlusion followed by 48 hours of reperfusion. Collateral flow was measured by radioactive microspheres. Infarct size and risk area were measured by a postmortem dual-perfusion technique using triphenyl tetrazolium chloride and Evan's blue dye. In eight dogs, therapy with DMTU (500 mg/kg i.v.) was given during the last 15 minutes of ischemia and the first 15 minutes of reperfusion. In eight control dogs, the same volume of 0.9% saline was given during the last 15 minutes of ischemia through the first 15 minutes of reperfusion. Infarct size as a percent of risk area was reduced in the DMTU-treated group compared with the saline-treated controls (DMTU = 42 +/- 4% versus saline = 59 +/- 4%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload. Modification by vitamin E deficiency.

To examine the role of oxidant damage to subcellular membranes in the pathogenesis of copper hepatotoxicity, the effects of dietary copper overload and varying states of vitamin E on biochemical, histological, and ultrastructural features of rat liver were investigated. Weanling male rats were pair-fed for 8 weeks on diets containing normal or high levels of copper in combination with either deficient, sufficient, or excessive vitamin E. Hepatic microsomes and mitochondria, isolated by differential centrifugation, showed similar enrichment and recovery among all experimental groups. Evidence of in vivo peroxidation of membrane lipids (generation of conjugated dienes and thiobarbituric acid reacting substances) was present in mitochondrial but not microsomal preparations from copper-overloaded rats. Serum aspartate aminotransferase, alanine aminotransferase, and cholylglycine (which were increased in all copper-overloaded rats), as well as mitochondrial thiobarbituric acid-reacting substances, were more elevated in vitamin E-deficient rats. In copper-overloaded rats, liver histology showed changes of acute and chronic hepatocyte injury with mild periportal fibrosis; electron microscopy showed abundant copper-containing lysosomes and dilated cristae of hepatocyte mitochondria, findings similar to those in the liver of humans with copper-overload disorders. These findings suggest that an oxidant injury to hepatocyte mitochondria may be one of the initiating factors in hepatocellular damage that leads to hepatic lesions in copper-overload states in humans.

Animals↗
PubMed1989

Biliary atresia: early determination of prognosis.

Analyses of bile bilirubin during the first month after Kasai operations, and of the liver biopsies obtained at the time of initial surgery, were done in 67 patients with biliary atresia. Bilirubin excretion (milligrams per day) was determined as the product of the bile volume and its concentration. Operative liver biopsies were evaluated for fibrosis, bile duct proliferation, bile stasis, giant cell transformation, and parenchymal degeneration; the severity of each abnormality was graded on a scale of 0 to 4. A forward stepwise regression procedure using the Cox proportional hazards model identified the relationship between survival and covariants. Thirty-nine of 67 patients died. Of these, 38 excreted less than 6 mg of bilirubin per day during the first postoperative month. The other patient died of a coexisting anomaly. Nine other patients who excreted less than 6 mg of bilirubin per day are alive but are either jaundiced or awaiting transplantation. Nineteen patients who excreted greater than or equal to 6 mg of bilirubin per day are alive (mean follow-up, 61 months) with normal or near-normal liver function. The severity of liver fibrosis, bile duct proliferation, and bile stasis did not correlate with survival, whereas giant cell transformation and parenchymal degeneration were highly significant (P less than or equal to .000 and P less than or equal to .0003, respectively). Twenty-six infants with grade 1-4 giant cell transformation or grade 2-4 parenchymal degeneration had a mean survival of 11 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1989

Lidocaine reduces canine infarct size and decreases release of a lipid peroxidation product.

Whether and how lidocaine reduced infarct size in a canine model of ischemia and reperfusion was investigated. Twenty dogs underwent a 90-min left anterior descending artery ligation and 300 min of reperfusion. Infarct size was measured by triphenyl tetrazolium chloride and the region at risk by 99Tc-labeled albumin microspheres injected during ischemia. In 10 dogs, lidocaine (70 micrograms/kg/min i.v.) was infused 90 min prior to and during ischemia and reperfusion, while 10 dogs were untreated. The ratio of infarct to risk area was 35.2 +/- 3.4% (SEM) in lidocaine dogs vs. 48.5 +/- 5.3% in untreated dogs (p less than 0.05). Lidocaine did not reduce neutrophil accumulation in ischemic and reperfused myocardium at 5 h of reperfusion, inhibit stimulated neutrophil superoxide production, or scavenge superoxide in vitro. However, during early reperfusion, lidocaine reduced coronary sinus levels of a lipid peroxidation product (conjugated dienes). Thus, clinically relevant lidocaine infusion rates reduced myocardial infarct size when given prior to and during ischemia and reperfusion. This protective effect may be due to lidocaine's membrane stabilizing effects, which could have protected the myocardial cell membrane from lipid peroxidation.

Animals↗
PubMed1989

Copper toxicity and lipid peroxidation in isolated rat hepatocytes: effect of vitamin E.

We investigated the role of lipid peroxidation as the mechanism mediating copper toxicity in isolated rat hepatocytes and the modulating effect of vitamin E. Hepatocytes, isolated from rats fed diets containing deficient (E-), sufficient (E+), and excess (E++) amounts of vitamin E, were incubated with CuCl2 (0-2400 microM) for 150 min. Dose and time-dependent decreases in hepatocyte viability (determined by trypan blue exclusion and lactate dehydrogenase release) due to copper toxicity correlated with production of malonyldialdehyde in E- and E+ hepatocytes. However, malonyldialdehyde generation did not accompany copper toxicity in E++ cells. Copper toxicity was enhanced in E- compared to E+ and E++ hepatocytes as assessed by cell viability studies and ultrastructural plasma membrane bleb formation. In vitro vitamin E repletion of E- hepatocytes restored resistance to copper and decreased malonyldialdehyde production proportionately. Thus vitamin E deficiency appeared to increase the susceptibility of hepatocytes to copper toxicity. We conclude that lipid peroxidation may not be the mechanism by which copper is toxic to isolated hepatocytes but that the site of injury may be thiol-rich cellular proteins.

Animals↗
PubMed1987

The surgery of "correctable" biliary atresia.

Seven of 114 (6%) patients treated in Denver for biliary atresia had a variant of the disease in which only microscopic bile ducts or ductules were identified at the porta hepatis, hepatic lesions were present, even in the neonatal example, and intrahepatic biliary hypoplasia was uniformly present. The excised bile duct cysts consisted of fibrosis or scar tissue and with little or no epithelial lining. Six patients had corrective surgery. The first patient was treated by choledochoenterostomy and became totally obstructed. Definitive operation in this patient and all subsequent patients consisted of excision of all extrahepatic duct structures and Roux-en-Y portoenterostomy. Two patients died, the one who did not have surgical correction and a second who had correction at age 35 weeks. The other five patients have been followed for 18 to 158 months and are anicteric but have some degree of residual liver damage. We conclude that so-called correctable biliary atresia occurs in less than 10% of cases, that because of coincident biliary hypoplasia, "cure" is not a possible outcome, and that the treatment of choice is complete surgical excision of the extrahepatic bile ducts and Roux-en-Y portoenterostomy.

Bile Ducts↗
PubMed1987

Surgical implications of bronchopulmonary dysplasia.

Twenty of 30 patients with bronchopulmonary dysplasia (BPD) had major tracheobronchial abnormalities, which in 18 could be incriminated as contributing to their symptoms. There were 15 examples of tracheobronchial stenosis, 13 of tracheomalacia, nine of bronchomalacia, and one of tracheal web. Sixteen patients had operations. Tracheostomy was successful as a temporizing measure in ten patients although there was significant morbidity. Balloon dilatation of tracheobronchial stenosis produced temporary (2) or long-term (2) improvement in four patients. Electroresection of tracheobronchial stenosis was successful in the three instances it was employed. Lobectomy for lobar emphysema was curative in both patients. Aortopexy for tracheomalacia improved all three patients. We conclude that (1) symptomatic major airway lesions are not uncommon manifestations of BPD, (2) many of the lesions are amenable to surgical therapy, and (3) bronchoscopic evaluation should be considered early in the course of infants with BPD.

Bronchopulmonary Dysplasia↗
PubMed1986

Biliary atresia in the newborn.

A prenatal sonographic diagnosis of extrahepatic biliary atresia was made and, 76 hours after birth, operatively confirmed. A standard Kasai operation was performed, with the exception of the use of an ancillary appendiceal conduit to provide biliary drainage of an independent bile duct draining the right anterior hepatic segment. Hepatic and ductal histology were identical to those usually found in biliary atresia in a 6- to 8-week-old infant. The child is well at 16 months.

Biliary Atresia↗
PubMed1986

Perinatal autopsy: its clinical value.

The clinical value of the routine autopsy was studied in 172 sequential cases of perinatal deaths. Of these cases 139 (81%) were autopsied including 52 fetal deaths and 87 neonatal deaths. The clinically assigned cause of death was compared with the cause of death as identified by the autopsy. In 26% (nine fetal and 27 neonatal deaths) the autopsy was the sole means of establishing the cause of death. A need for specific genetic counseling or evaluation was identified in 62 of the 139 perinatal deaths. In 30 (48%) cases the autopsy was the sole source of information highlighting this need. The autopsy is an important clinical tool providing useful information to the perinatal clinician. Besides providing specific causes of death, it can correct clinical impressions and identify genetic factors that require further assessment and counseling.

Autopsy↗
PubMed1984

In biliary atresia duct histology correlates with bile flow.

Three basic types of microscopic biliary structures at the portahepatis were distinguishable in infants with biliary atresia: bile ducts, collecting ductules of biliary glands, and biliary glands. Correlation between the type of biliary structure and the quantity and quality of post-operative bile flow was possible in 23 instances. At 2 weeks after operation, the 11 patients in whom a bile duct was identified had a daily bile flow of 68.0 +/- 11.5 mL. Bilirubin concentration in the bile was 13.6 +/- 3.3 mg/dL and total daily bilirubin excretion was 8.77 +/- 2.74 mg. In contrast, bile flow in 12 patients having only collecting ductules and/or biliary glands in the porta hepatis was 19.1 +/- 3.9 mL and bilirubin concentration in bile was 1.7 +/- 0.3 mg/dL. Thus, total daily bilirubin excretion was 0.34 +/- 0.08 mg (P less than 0.001). Postoperative cholangitis occurred only in patients with ducts. It is concluded that only bile ducts communicate with the intrahepatic biliary system and drain bile after hepatic portoenterostomy.

Bile↗
PubMed1984

Chronic sclerosing tracheobronchitis.

We report a child with wheezing and respiratory distress of 53 months duration which was undiagnosed and unresponsive to treatment. Necropsy examination of trachea and bronchi showed narrowing by chronic inflammation and fibrosis of mucosa and submucosa. Despite intensive investigations, the aetiology and pathogenesis remained undetermined.

Bronchi↗
PubMed1983

Hepatocellular carcinoma in young people.

The clinical and pathologic features of 23 cases of hepatocellular carcinoma occurring in patients younger than age 35 years (mean age, 17.4 years) were analyzed. Ten of these (43%) were the fibrolamellar oncocytic variant (FLO), characterized by large polygonal neoplastic hepatocytes and lamellar bundles of collagen. The remainder (non-FLO) showed the usual wide range of gross and histologic patterns typical of hepatocellular carcinoma in older age groups. Overall, hepatocellular carcinoma was more common in females than in males. The FLO variant was characterized by a longer duration of symptoms prior to diagnosis, increased frequency of resectability of the tumor, and infrequency of mitoses. Of particular importance is the fact that 5 of 10 patients with the FLO variant are alive and clinically free of disease 1 1/2 to 8 years postoperatively, while none of the 13 patients with non-FLO hepatocellular carcinoma is alive and free of disease. There was no significant difference between the two groups in mean age at diagnosis, presence of single versus multiple hepatic tumors, vascular invasion, or tumor necrosis. Although cirrhosis was present in three non-FLO patients and none of the FLO patients, the difference was not statistically significant. The prognosis of hepatocellular carcinoma in young patients does not appear to differ from that in older patients, with the exception of the fibrolamellar oncocytic variant, a variant which is common in younger patients.

Adolescent↗