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Biomedical subjects

J B Atkinson

Publications and source records attributed to J B Atkinson.

At least 73 records · Page 4Linked to original sources

Growth hormone effects on wound healing in malnourished animals: a histological study.

Systemic growth hormone (GH) markedly improves celiotomy wound strength in protein malnourished (PM) animals. This study was undertaken to analyze the effect of GH as a basis for anatomically understanding. Adult female Spraque-Dawley rats were divided into normally nourished controls, PM and GH-treated PM groups. Protein malnutrition was achieved by feeding 5.5% protein restricted chow every other day for eight weeks before surgery. Controls were fed 23.4% protein chow. All animals were fed 23.4% protein chow postoperatively. Rat-GH was injected subcutaneously twice daily (1.0 mg/day) for three days prior to and five days after 5 cm midline celiotomy. Bursting strength of the wound was measured at 3, 6 and 14 days postoperatively. Histologic wound specimens (hematoxylin and eosin) were obtained from each group. Wound strength of malnourished rats was significantly less than that of normal controls at six days after operation (p < 0.001). With administration of growth hormone, the wound strength was significantly improved. Histologically, there was no difference between groups on day 3. On day 6 the normal control group showed a decrease in the early inflammatory cell infiltrate with concurrent development of granulation tissue and a dense proliferation of fibroblasts. The PM wound showed fatty infiltration, a very narrow band of poorly formed granulation tissue and a sparse fibroblastic proliferation. The GH-treated PM group showed a combination of histologic findings. Fatty infiltration, similar to that in malnourished non-treated animals, was still evident but there was also a dense proliferation of capillary channels and fibroblasts comparable to normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term histologic patency after percutaneous transluminal coronary angioplasty is predicted by the creation of a greater lumen area.

OBJECTIVES: This study assessed the relation between histologic acute and long-term lumen size after coronary angioplasty. BACKGROUND: Angiographic studies suggest that the creation of a larger acute lumen is associated with a reduced incidence of restenosis. Histologic evaluation of the influence of the acute lumen on late outcome has not been previously reported. METHODS: Detailed histologic examination and planimetry were performed in 28 postmortem coronary arteries subjected to angioplasty at an average of 71 weeks antemortem. The lumen area on each histologic segment was defined as the final lumen area. The lumen area immediately after angioplasty, the acute lumen area, was defined by the sum of the neointimal area plus final lumen. A final lumen area > or = 25% of the arterial area was considered a long-term success; a final lumen area < 25% was considered a long-term failure. RESULTS: Arterial size and neointimal area were similar in long-term successes and failures. In successes, the mean (+/- SD) acute lumen area was greater than in failures (4.1 +/- 1.9 vs. 2.7 +/- 1.4 mm2, respectively, p < 0.001). The acute lumen area as a percent of arterial area was 46 +/- 10% in successes versus 27 +/- 11% in failures (p < 0.0001). The corresponding estimated mean acute lumen diameter stenosis was 24 +/- 8% in successes versus 42 +/- 12% in failures (p < 0.0001). Plaque area was greater in failures (7.1 +/- 3.2 mm2) than in successes (4.8 +/- 2.4 mm2, p < 0.002). CONCLUSIONS: Neointimal proliferation after angioplasty occurs in all dilated coronary arteries, and the amount of neointimal growth is independent of vessel size. The creation of a larger lumen and a larger lumen as a percent of vessel size were associated with an improved long-term histologic patency.

Angioplasty, Balloon, Coronary↗

Reperfusion enhances the local release of endothelin after regional myocardial ischemia.

The role of endothelin, a potent long-acting vasoconstrictor peptide, in the pathogenesis of the "no-reflow" phenomenon was investigated in nine closed-chest mongrel dogs undergoing 90 minutes of proximal left anterior descending artery occlusion and 3.5 hours of reperfusion. Endothelin levels were measured serially from the coronary sinus (CS) and aorta (Ao) by radioimmunoassay and correlated with regional myocardial blood perfusion. Prolonged anesthesia, surgery, and vascular instrumentation did not change endothelin levels in four sham animals. A progressive and parallel increase in CS and Ao endothelin levels occurred during coronary occlusion. A further increase in CS levels was observed during the reperfusion period, resulting in significantly higher values of the peptide at 30 and 60 minutes (30 minutes: CS 22.1 +/- 3.5 vs Ao 15.1 +/- 5.1 pg/ml; 60 minutes: CS 21.1 +/- 4.5 vs Ao 15.0 +/- 3.6 pg/ml; p < 0.05 by analysis of variance). Microvascular perfusion determined semiquantitatively with fluorescent beads was significantly reduced in the central ischemic zone (CIZ) compared with that in the nonischemic zone (NIZ) (CIZ endocardium 1.14 +/- 0.4 beads/m2, CIZ midmyocardium 1.19 +/- 0.3 beads/m2, NIZ 3.8 +/- 0.6 beads/m2; p < 0.05). A significant correlation was noted between mean reperfusion levels of endothelin in the CS and endocardial flow in the CIZ (r = -0.88; p = 0.009). This study demonstrates that reperfusion per se enhanced the spillover of endothelin from the cardiac interstitium. Local release of endothelin may contribute to the progressive decrease in microvascular flow in the reperfused bed.

Animals↗

Maintaining long-term central venous access by repetitive hepatic vein cannulation.

Long-term central venous access has become a critical issue in the treatment of pediatric patients. Exhaustion of access sites can lead to superior and inferior vena cava thrombosis, limiting the choices for central line placement. Under such circumstances, hepatic vein cannulation is a viable option. We present the cases of two patients who, combined, have undergone five hepatic vein catheterizations. One patient has received four consecutive central lines via a hepatic vein. This experience suggests that the hepatic vein is a reusable site of cannulation in patients with no other alternative for venous access.

Catheterization, Central Venous↗

Overcoming a kinked peel-away sheath during central line implantation.

In pediatric patients, central line implantation via the subclavian vein can be complicated by the presence of a kink in the peel-away sheath. A technique is described, which has been used on 62 occasions to overcome this problem. Reinserting the catheter through the kinked peel-away sheath in concert with a guidewire that extends 3 to 4 cm beyond the catheter tip can ensure successful placement.

Catheterization, Central Venous↗

A prospective randomized trial of delayed versus immediate repair of congenital diaphragmatic hernia.

From March 1990 to January 1993, a randomized prospective study was performed to determine the optimal timing of surgery for infants with high-risk congenital diaphragmatic hernia (CDH). Thirty-two CDH patients who presented with respiratory distress within 12 hours after birth were randomly divided into two groups: Group A had early repair (within 6 hours), and group B had delayed repair (at 96+ hours). Extracorporeal membrane oxygenation (ECMO) was initiated in both groups as necessary. Fourteen patients were assigned to group A, and 18 were assigned to group B. Two patients initially assigned to group A had acute deterioration, and their operations had to be postponed. Data were collected, but these patients were eliminated from the study. The two groups were comparable based on gestational age, birth weight, Bohn's criteria, and oxygenation and ventilatory index. Nine of 12 group A patients (75%) survived, and 13 of 18 group B patients (72%) survived (P > .05, not significant). The ECMO requirements for the two groups were not significantly different (8 of 12 (67%) v 16 of 18 (89%); P > .05). Surgical intervention for bleeding complications related to ECMO was required in three of eight (38%) with immediate repair and seven of 16 (44%) with delayed repair (P > .05). There was no difference in survival nor incidence of ECMO between the two groups. This is the first prospective study of timing of hernia repair that supports the conclusions of earlier reports of retrospective studies.

Extracorporeal Membrane Oxygenation↗

The association of mast cells and atherosclerosis: a morphologic study of early atherosclerotic lesions in young people.

Mast cell products, such as histamine, may contribute to the initiation and progression of the atherosclerotic plaque. To determine the relationship that may exist between early atherosclerotic plaques and mast cells we studied the aortas and coronary arteries of 115 young subjects aged 15 to 34 years who had traumatic deaths. Lesions were classified as normal intima, fatty streaks, fibro-fatty plaques, and fibrous plaques. Aortic and coronary artery segments with raised lesions had significantly greater numbers of mast cells in the adventitia (and occasionally intima and outer media) compared with those with a normal intima. In the aortic segments greater numbers of mast cells were located in the dorsal portion (lesion "prone") compared with the ventral half (lesion "resistant") (P < .05). These data support the concept that increased numbers of mast cells are associated with atherosclerosis and suggest a role for mast cell products in the evolution of the atherosclerotic plaque.

Adolescent↗

Allogeneic versus autologous purged bone marrow transplantation for neuroblastoma: a report from the Childrens Cancer Group.

PURPOSE: We have compared the toxicity, relapse rate, and progression-free survival (PFS) of high-risk neuroblastoma patients receiving identical induction therapy and myeloablative chemotherapy plus total-body irradiation (TBI) followed by allogeneic or autologous purged bone marrow transplantation (BMT). PATIENTS AND METHODS: Fifty-six patients with high-risk neuroblastoma underwent BMT at investigator and parent option if they did not have progressive disease after induction chemotherapy with cisplatin, cyclophosphamide, doxorubicin, and etoposide. After surgery and local radiation to residual tumor, myeloablative therapy consisting of etoposide, melphalan, cisplatin, and TBI was given followed by BMT. Patients with human leukocyte antigen (HLA)-compatible siblings received allogeneic bone marrow (n = 20). The remaining patients (n = 36) received autologous bone marrow that had undergone multimodality purging and had no remaining detectable tumor cells by immunocytology. RESULTS: Four of 20 allogeneic patients had a treatment-related death, compared with three of 36 autologous patients (P = .21). The relapse rate among allogeneic BMT patients was 69%, compared with 46% for autologous BMT patients (P = .14). The estimated PFS rates 4 years after BMT were 25% for allogeneic BMT patients and 49% for autologous BMT patients (P = .051). CONCLUSION: Overall outcome for patients with neuroblastoma given this same induction therapy followed by autologous purged marrow was similar to that with allogeneic marrow, although bias in patients selection cannot be excluded in a nonrandomized comparison.

Adolescent↗

Urokinase versus recombinant tissue plasminogen activator in thrombosed central venous catheters: a double-blinded, randomized trial.

Fifty dysfunctional central venous catheters proven radiographically to be occluded by thrombus were blindly randomized to be injected with either 2 mg recombinant tissue plasminogen activator (t-PA) or 10,000 units of urokinase (UK) and allowed to incubate for 2 h. A second dose was allowed if catheter function was not restored with the first injection. Repeat radiograph contrast injection was done when catheter function was restored or after 2 doses of study drug were administered, whichever occurred first. Thirteen of 22 catheters randomized to UK had full function restored compared to 25 of 28 randomized to t-PA (p = 0.013). Radiographic contrast injection showed 7 catheters randomized to UK had complete resolution of the thrombus compared to 17 randomized to t-PA (p = 0.042). Four catheters randomized to UK had complete resolution of the thrombus after a single dose compared to 13 randomized to t-PA (p = 0.036). A novel dose of 2 mg of t-PA restored catheter function more reliably and dissolved thrombi faster than twice the standard, FDA-approved dose of UK.

Adult↗

Noninvasive detection of acute rejection in a new experimental model of heart transplantation.

We have shown that positron emission scintigraphy detects changes in the uptake of 18-F 2-deoxyglucose and 13-N ammonia by the acutely rejecting myocardium in a nonworking model of heterotopic heart transplantation in the rat. We developed a new working model of heterotopic heart transplantation to determine the possible relevance of these changes to clinical transplantation. Moderate aortic valvular regurgitation was produced allowing the heterotopic left ventricle to fill and eject. Rejecting allografts and nonrejecting isografts (controls) were studied 4 days after transplantation. Histologically, isografts were normal and all allografts showed mild acute rejection. Decay-corrected uptakes of 18-F 2-deoxyglucose and 13-N ammonia reflect glucose metabolism and blood flow, respectively. Values are presented as percent of injected dose per gram of tissue. Uptake of 18-F 2-deoxyglucose was higher in rejecting allografts compared with nonrejecting isografts (3.0 +/- 1.8 versus 1.1 +/- 0.4; p = 0.024). Ammonia uptake was elevated in allografts compared with isografts (2.2 +/- 0.5 versus 1.3 +/- 0.5; p = 0.023). Uptakes of 18-F 2-deoxyglucose and 13-N ammonia are higher in mildly rejecting allografts, implying increased glucose utilization and blood flow during acute rejection. These data support our earlier findings of changes in myocardial metabolism in the absence of diminishing blood flow in acutely rejecting hearts. This model may lead to a better understanding of the physiology and metabolism of acute rejection.

Animals↗

Management of splenic abscess in immunocompromised children.

Splenic abscess is an infrequent complication in the immunocompromised patient. Six patients underwent splenectomy for presumed splenic abscess from 1987 to 1991. Chemotherapy altered the immune system of four patients; the human immunodeficiency virus (HIV) rendered the other two vulnerable to infection. Five presented with fever but none had leukocytosis; only one exhibited palpable splenomegaly; three had abdominal pain. Cultures documented systemic infection in all but one, an HIV-positive individual. Respiratory embarrassment was the indication for surgery in one patient. In five cases the decision for surgical intervention was made after computed tomography (CT) indicated the presence of multiple splenic lesions and systemic antibiotics failed to resolve the fevers. CT additionally showed hepatic and/or renal microabscesses in four patients. Signs and symptoms experienced preoperatively resolved with splenectomy in all six patients. No additional surgery was required for the patients with extrasplenic abscesses. Surgical pathology determined that three spleens had fungal and two had mycobacterial abscesses. The other was shown to be a spindle cell sarcoma; no abscess was present. This patient had preoperative blood cultures positive for mycobacteria, and the same organism was recovered from retroperitoneal nodes sampled at the time of splenectomy for the sarcoma. Follow-up indicates that no patients experienced surgical complications or sequelae related to their splenic pathology. Splenectomy is necessary and effective in treating splenic abscesses in immunocompromised patients and is appropriate for diagnosis as well as therapy.

Abscess↗

Ventricular defibrillation in canines with chronic infarction, and effects of lidocaine and procainamide.

Prior studies in dogs with normal hearts have demonstrated that lidocaine increases but procainamide does not change the energy required for successful defibrillation. Because many postinfarct patients receiving implantable cardioverter defibrillator devices require adjunctive antiarrhythmic therapy, we have studied the effects of lidocaine and procainamide on the relationship between delivered voltage and defibrillation success in mongrel dogs 21 +/- 3 days following ligation of the left anterior descending and first diagonal coronary arteries. Internal defibrillation testing using a patch-patch electrode configuration was performed before and during the administration of saline controls (n = 10), lidocaine (n = 10) and procainamide (n = 10). The mean infarct size as determined by staining with tetrazolium was 13.4% +/- 8.3% of right and left ventricles, and did not differ significantly between groups. The 50% effective defibrillation (ED50) voltage increased with infusions of saline (16% +/- 15%), lidocaine (40% +/- 22%), and procainamide (13% +/- 15%) and the ED50 energy increased 41% +/- 44%, 104% +/- 62%, and 35% +/- 36%, respectively. However, the increase in ED50 voltages and energies were significantly greater in animals receiving lidocaine compared to those receiving either saline control or procainamide (P < 0.01). There were trends toward change of hemodynamic parameters in all animals following baseline defibrillation testing; stroke volume declined 21% +/- 16%; and mean pulmonary artery and aortic pressure increased by 22% +/- 25% and 11% +/- 15%, respectively. In conclusion, unlike our previous studies in dogs with normal hearts, in this model hemodynamic deterioration occurred with repeated fibrillation and defibrillation, and defibrillation voltage requirements increased in the control series. Taking into consideration the increase in defibrillation voltage requirements over the duration of the experiments, lidocaine increases and procainamide does not change ED50; thus, their effects are similar in normal and infarcted canine hearts.

Animals↗

Molecular forms of atrial natriuretic factor in normal and failing human myocardium.

BACKGROUND: Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart. METHODS AND RESULTS: We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF. CONCLUSIONS: These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.

Adolescent↗

Doxorubicin cardiomyopathy is associated with a decrease in calcium release channel of the sarcoplasmic reticulum in a chronic rabbit model.

Doxorubicin is a highly effective cancer chemotherapeutic agent that produces a dose-dependent cardiomyopathy that limits its clinical usefulness. Clinical and animal studies of morphological changes during the early stages of doxorubicin-induced cardiomyopathy have suggested that the sarcoplasmic reticulum, the intracellular membrane system responsible for myoplasmic calcium regulation in adult mammalian heart, may be the early target of doxorubicin. To detect changes in the calcium pump protein or the calcium release channel (ryanodine receptor) of the sarcoplasmic reticulum during chronic doxorubicin treatment, rabbits were treated with intravenous doxorubicin (1 mg/kg) twice weekly for 12 to 18 doses. Pair-fed controls received intravenous normal saline. The severity of cardiomyopathy was scored by light and electron microscopy of left ventricular papillary muscles. Developed tension was measured in isolated atrial strips. In subcellular fractions from heart, [3H]ryanodine binding was decreased in doxorubicin-treated rabbits (0.33 +/- 0.03 pmol/mg) compared with control rabbits (0.66 +/- 0.02 pmol/mg; P < 0.0001). The magnitude of the decrease in [3H]ryanodine binding correlated with both the severity of the cardiomyopathy graded by pathology score (light and electron microscopy) and the decrease in developed tension in isolated atrial strips. Bmax for [3H]ryanodine binding and the amount of immunoreactive ryanodine receptor by Western blot analysis using sequence-specific antibody were both decreased, consistent with a decrease in the amount of calcium release channel of sarcoplasmic reticulum in doxorubicin-treated rabbits. In contrast, there was no decrease in the amount or the activity of the calcium pump protein of the sarcoplasmic reticulum in doxorubicin-treated rabbits. Doxorubicin treatment did not decrease [3H]ryanodine binding or the amount of immunoreactive calcium release channel of sarcoplasmic reticulum in skeletal muscle. Since the sarcoplasmic reticulum regulates muscle contraction by the cyclic uptake and release of a large internal calcium pool, altered function of the calcium release channel could lead to the abnormalities of contraction and relaxation observed in the doxorubicin cardiomyopathy.

Animals↗

Patterns of relapse after autologous purged bone marrow transplantation for neuroblastoma: a Childrens Cancer Group pilot study.

PURPOSE: The goal of this investigation was to determine if comparing sites of neuroblastoma at relapse after myeloablative chemoradiotherapy and purged autologous bone marrow transplantation (ABMT) with sites of disease at diagnosis and before ABMT could provide insight to the reasons for treatment failure. PATIENTS AND METHODS: Ninety-nine patients with high-risk neuroblastoma underwent ABMT after induction chemotherapy, surgery +/- local radiation (RT) and then myeloablative therapy with teniposide (or etoposide), melphalan, doxorubicin, cisplatin, and total-body irradiation (TBI). RESULTS: Forty-one of 84 assessable patients (15 toxic deaths) developed progressive disease 1 to 44 months after ABMT. The overall probability of relapse 36 months after ABMT was 49%. Tumor recurred in primary (n = 22), bone (n = 20), bone marrow (n = 18), lung (n = 3), and other sites (n = 9). Eight patients relapsed in the primary site alone, 14 in primary and distant sites, and 19 in distant sites only. Of 41 patients with progressive disease, 33 have died, with a median interval from relapse to death of 4 months. Both bone and bone marrow involvement at diagnosis correlated with specific relapse in that site (P < .05). Bone marrow tumor content at harvest greater than 0.1% also correlated with bone marrow relapse (P = .001). There was an association between incomplete resection of the primary tumor at diagnosis and relapse in that site (P = .06). CONCLUSION: Neuroblastoma normally recurs in multiple sites after ABMT, particularly in areas of previous disease. More intensive treatment to known areas of disease (aggressive early surgery, effective myeloablative consolidation therapy) and post-ABMT therapy for minimal residual disease should be studied for their potential to decrease the frequency of relapse.

Adolescent↗

Management of pulmonary blastoma in children.

Pulmonary blastoma is a rare neoplasm, accounting for 0.5 per cent of all primary malignant pulmonary tumors. The clinical features, radiologic findings, and management of five children with pulmonary blastoma are described. The female/male ratio was 4:1. Mean age at presentation was 34 months, with a mean duration of symptoms of 1.8 months. Fever and cough were the most common symptoms. Opacification of the right lung field with mediastinal shift to the left was the predominant roentgenologic feature. The tumor involved the right chest in all patients. Thoracotomy was performed in all patients to establish the diagnosis. Two patients underwent complete resection at the initial operation, an incomplete resection was performed in one patient. Delayed complete resection was performed in another patient. All the patients received combination chemotherapy and one patient also received radiotherapy for primary disease. Two patients with histologic and immunohistochemical evidence of striated muscle differentiation were treated as rhabdomyosarcomas. Both these patients have survived for 24 and 67 months after diagnosis. The tumor recurred in three patients. Recurrence was treated with a combination of surgery, chemotherapy, and radiotherapy. Overall disease-free survival rate was 40 per cent. Long-term follow-up and additional patients are required to provide prognostic information.

Antineoplastic Combined Chemotherapy Protocols↗