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A R Buckley

Publications and source records attributed to A R Buckley.

88 records · Page 5Linked to original sources

The distinction between acute renal transplant rejection and cyclosporine nephrotoxicity: value of duplex sonography.

Although sonography is useful in the evaluation of renal transplants, there are no objective sonographic findings for reliably differentiating acute rejection from cyclosporine nephrotoxicity. This study was undertaken to determine the role of pulsed Doppler flow analysis (duplex sonography) in making this distinction. Duplex Doppler sonography was performed in 106 patients with normally functioning transplanted kidneys and in 34 patients with renal transplant dysfunction who underwent percutaneous biopsy. Renal vascular impedance was estimated in the segmental, interlobar, and arcuate arteries by calculating the ratio of end-diastolic minimum velocity to systolic peak velocity (diastolic/systolic ratio). In the healthy control subject, the diastolic/systolic velocity ratios varied in the different arterial segments, ranging from a mean of 0.23 in the segmental arteries to a mean of 0.32 in the arcuate arteries. Seventeen patients experienced acute rejection: eight of the nine with acute vascular rejection had abnormal Doppler ratios; eight patients with acute cellular rejection had normal ratios. Nine patients with cyclosporine nephrotoxicity all had normal duplex scans. Seven patients with chronic rejection had normal ratios. One patient with hemolytic-uremic syndrome had an abnormal flow pattern. These findings indicate that duplex sonography may be useful in differentiating acute vascular rejection from cyclosporine nephrotoxicity in the transplanted kidney.

Adult↗

Intraoperative imaging of the biliary tree. Sonography vs. operative cholangiography.

The accepted technique for diagnosing choledocholithiasis at the time of cholecystectomy is operative cholangiography. Reports in the surgical literature suggest that intraoperative ultrasound can replace operative cholangiography in the accurate detection of common duct stones. This prospective study was performed jointly by radiologists and surgeons together in the operating room. Twenty-one patients underwent intraoperative ultrasonography and operative cholangiography at the time of cholecystectomy. In the 16 cases in which both studies were adequate, there were 11 in which no stones were seen on either; three in which stones were seen on both; and two in which stones were diagnosed by sonography alone. In one of these latter cases, the stones were confirmed, making the cholangiogram falsely negative. In the other case, no stones were found so we presume that sonography was falsely positive. Although this technique can be accurate and useful, it is technically demanding, even for an experienced sonologist. We feel that this technique is likely to be of benefit only to the surgeon with considerable ultrasound training, expertise, and motivation.

Adult↗

Predicting failure in polytetrafluoroethylene vascular access grafts for hemodialysis: a pilot study.

In order to determine if serial, noninvasive evaluation of polytetrafluoroethylene (PTFE) vascular access grafts could identify a subgroup of patients at risk for thrombosis, the authors studied flow characteristics, using duplex ultrasonic scanning, in 18 hemodialysis patients with forearm loop grafts. On average, five examinations were performed per patient over the 10-month study period. Seven episodes of thrombosis occurred in six patients. The mean Doppler flow in grafts that subsequently thrombosed was significantly lower than in those that did not (544 +/- 218 ml/min versus 843 +/- 391 ml/min, p less than 0.001). The interval from last examination to thrombosis ranged from 13 to 58 days. At a defined cut-off flow of 450 ml/min, this test yielded a sensitivity of 83% and a specificity of 75% for episodes of thrombosis occurring within 2 to 6 weeks. The authors conclude that episodes of thrombosis in PTFE arm loop grafts are usually preceded by significantly lower Doppler-measured flow than grafts that do not thrombose and that it may be possible, by this means, to identify grafts at risk.

Blood Vessel Prosthesis↗

Prolactin administration stimulates rat hepatic DNA synthesis.

Prolactin is an important growth modulatory hormone in fetal and adult tissues. Its administration stimulates enzymatic markers of the G1 phase of cell cycle in rat liver and other tissues. To determine the effects of prolactin administration on hepatic DNA synthesis (S phase), rats received prolactin at 12 hour intervals for 48 hours and DNA synthesis was assessed by [3H]-thymidine incorporation. Prolactin administration stimulated DNA synthesis 2-4 fold above controls in the livers of adult and weanling animals. Increased incorporation of radiolabel was associated with the nucleus of hepatoparenchymal cells. These data support the hypothesis that prolactin may be a physiological regulator of hepatic DNA synthesis. Further, since stress stimulates prolactin secretion, we suggest that prolactin may participate in the hepatic compensatory hyperplasia elicited by the stress associated with partial hepatectomy.

Age Factors↗

Prolactin stimulation of ornithine decarboxylase and mitogenesis in Nb2 node lymphoma cells: the role of protein kinase C and calcium mobilization.

The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with calcium ionophores has been shown to bypass the requisite antigen- or lectin-induced signal for lymphocyte mitogenesis. This suggests that protein kinase C activation and calcium mobilization may be early events required for lymphocyte proliferation. Therefore, the relationship(s) of protein kinase C activation and calcium mobilization to ornithine decarboxylase induction and cellular proliferation were examined in a rat node lymphoma cell line (Nb2) which is dependent upon prolactin (PRL) for mitogenesis. TPA enhanced PRL-stimulated Nb2 node lymphoma cell ornithine decarboxylase induction and [3H]thymidine incorporation. Addition of a calcium ionophore (A23187) to cultures containing TPA plus PRL increased ornithine decarboxylase above PRL alone or PRL plus TPA but inhibited proliferation compared to the PRL plus TPA regimen. Exposure of cells to TPA or TPA plus A23187 increased [3H]thymidine incorporation in a similar manner to that demonstrated for low-dose PRL. However, optimal concentrations were only 20-25% as effective as mitogens as was optimal PRL. Protein kinase C and calmodulin antagonists inhibited PRL-stimulated ornithine decarboxylase induction and proliferation. Ca2+ chelation or cation channel antagonism inhibited both PRL-stimulated responses. The cyclic AMP analogue, 8Br-cAMP, inhibited PRL-stimulated ornithine decarboxylase activity as well as cellular proliferation processes assessed by [3H]thymidine incorporation. Finally, tumor-promoting phorbol esters inhibited 125I-rPRL binding. These data strongly suggest that protein kinase C activation and calcium mobilization are requisite events for PRL-stimulated ornithine decarboxylase induction and cellular proliferation in Nb2 node lymphoma cells. An additional component that is linked to alterations in K+ channeling is also implicated. These data support a role for protein kinase C in PRL-coupled mitogenesis. However, other critical Ca2+ and/or ion-induced events are also required.

Animals↗

Prolactin is a tumor promoter in rat liver.

Since prolactin, like the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate, induces ornithine decarboxylase and plasminogen activator activities, biochemical markers of a trophic response, this hormone might likewise promote neoplasia. To test this theory, rats were initiated with a hepatocarcinogen followed by six weeks of ovine prolactin. This regimen caused hepatomegaly and the development of enzyme-altered foci. Promotion with prolactin for 23 weeks further increased the numbers of enzyme-altered foci. We suggest that prolactin is an endogenous tumor promoter for chemically initiated cells.

Animals↗

In vivo induction of rat hepatic ornithine decarboxylase and plasminogen activator by 12-O-tetradecanoylphorbol 13-acetate.

Rapid and substantial elevations in ornithine decarboxylase and plasminogen activator have been linked to tumor promotion in mouse epidermis and in vitro. Systemic administration of 12-O-tetradecanoylphorbol 13-acetate (TPA) rapidly increased both enzymic activities in rat liver. Pretreatment with either cycloheximide or actinomycin D attenuated both enzyme inductions. It is concluded that: (1) systemic TPA rapidly induces plasminogen activator and ornithine decarboxylase activities in rat liver; and (2) both inductions reflect de novo enzyme synthesis.

Animals↗

Rapid elevation of plasminogen activator activity in rat tissues by prolactin.

Administration of ovine prolactin resulted in a rapid and significant induction of plasminogen activator activity within two hours in the rat adrenal gland, heart, aorta and liver. Prolactin exposure reduced baseline proteolytic activity in lung and skeletal muscle at 6-8 hours following hormonal challenge. This was coincident with a return toward baseline levels in enzyme activity demonstrated in other tissues. Pretreatment with actinomycin D or cycloheximide ameliorated the enzymic induction in the liver and adrenal and partially inhibited the aortic response. These data suggest that prolactin exposure leads to increased proteolytic activity through de novo biosynthesis in a variety of solid organs. In addition, pro-enzyme activation may also occur in vascular tissue.

Animals↗

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Carbon Monoxide Poisoning↗

The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine.

Hepatic neutral serine proteases (including plasminogen activator) and ornithine decarboxylase (ODC) are induced by the hepatotoxin galactosamine (GALN). We examined the hepatoprotection conferred by epsilon-aminocaproic acid (EACA), a fibrinolytic inhibitor, putrescine (PUTR), the polyamine generated from ornithine by ODC, and alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. GALN, 450 mg/kg, was administered intraperitoneally to Wistar-Lewis rats (group I). Groups II, III, and IV were also given EACA (80 mg/kg), PUTR (0.3 mmol/kg), or DFMO (0.3 mmol/kg), respectively, 1 hour before and 3, 7, and 12 hours after GALN. Rats were killed 2 hours after an intraperitoneal dose of 3H-thymidine was administered, 30 or 45 hours after GALN. EACA and PUTR were effective protectants against necrosis as judged by enzymes and histologic findings. Neither increased thymidine incorporation above the levels seen with GALN only. DFMO offered no protection even though thymidine incorporation at 45 hours was increased. Both EACA and PUTR, which have similar chemical structures, possessed significant antiprotease activity in vitro, suggesting that they act by inhibiting toxin-induced neutral serine protease activity and not by accelerating regeneration.

Aminocaproates↗

Rapid fibrin D-dimer tests for deep venous thrombosis: factors affecting diagnostic utility.

Measurement of fibrin D-dimer may be a useful diagnostic test to exclude a diagnosis of deep venous thrombosis (DVT) in the emergency department setting. However, the specific assay format may influence its sensitivity and ultimate clinical utility. We tested samples from 200 patients under evaluation for DVT using three fibrin D-dimer assays: the SimpliRED whole blood agglutination assay, a latex agglutination assay, and the Dimertest EIA. Latex agglutination assays were performed in both a specialized laboratory and a routine laboratory. The negative predictive value for all tests was > 90%. The sensitivity of the SimpliRED assay was similar to that of the latex assay. The sensitivity of the latex assay was significantly lower when performed by generalist laboratory technologists. Thus, while D-dimer may be a useful test for the exclusion of DVT, subjective endpoint latex agglutination assays should be performed only by appropriately trained personnel.

Adolescent↗