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Biomedical subjects

G J Berry

Publications and source records attributed to G J Berry.

At least 37 records · Page 2Linked to original sources
PubMed2000

Combined immunosuppression with cyclosporine (neoral) and SDZ RAD in non-human primate lung transplantation: systematic pharmacokinetic-based trials to improve efficacy and tolerability.

BACKGROUND: We studied the efficacy and tolerability of combined immunosuppressive therapy with cyclosporine A microemulsion (Neoral) plus the macrolide SDZ RAD 40-0 (2-hydroxyethyl) rapamycin (RAD) in a stringent cynomolgus monkey lung graft model in comparison with cyclosporine or SDZ RAD monotherapy. METHODS: Thirty-nine cynomolgus monkeys received mixed lymphocyte reaction (MLR) mismatched unilateral lung transplants. Immunosuppressants were administered orally as single daily doses. The observation period was 28 days and follow-up included serial trough blood drug concentrations measured by high performance liquid chromatography/mass spectrometry, blood analyses, chest radiographs, open lung biopsies, as well as tissue drug concentrations and graft histology at necropsy. RESULTS: Graft biopsies in monkeys treated with vehicle (n=4), Neoral (day 1-7: 150 mg/kg/day; day 8-28: 100 mg/kg/day; n=6; mean +/- SE trough level (MTL): 292+/-17 ng/ml) or SDZ RAD monotherapy (1.5 mg/kg/day; n=6; MTL: 15+/-1 ng/ml) showed severe rejection. Coadministration in two transplant monkeys of Neoral (150/100 mg/kg/day) and SDZ RAD (1.5 mg/kg/day) caused their early death. In both animals, SDZ RAD blood levels were more than 5-fold higher than under monotherapy (MTL: 82+/-18 ng/ml). Simultaneous administration (n=6) of Neoral (150/100 mg/kg/day; MTL: 217+/-16 ng/ml) and SDZ RAD (0.3 mg/kg/day; MTL: 24+/-2 ng/ml) improved graft outcome (mild rejection). Side effects included renal failure (n=2) and seizures (n=1). Three monkeys survived to day 28. In this group the MTL for cyclosporin was 143+/-13 and for RAD 38+/-3. Staggered treatment completely prevented rejection in four of six grafts. However, five of six monkeys had moderate to severe diarrhea. In a concentration-controlled trial of simultaneously administered Neoral and SDZ RAD in transplant monkeys (target SDZ RAD MTL: 20-40 ng/ml; cyclosporine MTL: 100-200 ng/ml) all six monkeys survived with improved drug tolerability and an average biopsy score of mild rejection. CONCLUSION: Combination of orally administered SDZ RAD and Neoral showed excellent immunosuppressive efficacy in a stringent lung transplant model. The drug interaction and the narrow therapeutic index of this drug combination required careful dose adjustments to optimize tolerability and efficacy.

Animals↗
PubMed2000

Influenza pneumonia in a paediatric lung transplant recipient.

Although a common cause of morbidity and mortality in the general population, influenza infections are uncommon in lung transplant recipients and, to date, have only been associated with transient declines in pulmonary function and a relatively benign clinical course. This paper describes severe influenza pneumonia in a 13-year-old paediatric lung transplant recipient (5 months after double lung transplantation). Influenza pneumonia was diagnosed by direct fluorescent antibody testing and viral culture of bronchoalveolar lavage fluid. The patient required mechanical ventilation for 2 days due to respiratory failure and fatigue. Since his recovery from this pneumonia, he has developed obliterative bronchiolitis and currently awaits re-transplantation.

Adolescent↗
PubMed2000

Successful treatment of acute, ongoing rat lung allograft rejection with the novel immunosuppressant SDZ-RAD.

BACKGROUND: Recent experimental data have shown that coadministration of microemulsion cyclosporine and the novel immunosuppressant SDZ-RAD potentiates the immunosuppressive efficacies of both drugs to suppress allograft rejection. Our study was designed to assess the potential of delayed SDZ-RAD administration, in addition to cyclosporine maintenance therapy, to reverse acute rejection in an allogeneic rat lung transplant model. METHODS: Unilateral left lung transplantation was performed using Brown-Norway donors implanted into Lewis recipients. An untreated control group and a cyclosporine monotherapy group (7.5 mg/kg) were followed for 7 days. An additional cyclosporine monotherapy group (7.5 mg/kg), and a combined therapy group treated with cyclosporine (7.5 mg/kg) plus SDZ-RAD (2.5 mg/kg), were followed for 21 days. For treatment of ongoing rejection, 7.5 mg/kg cyclosporine was given as maintenance therapy, and SDZ-RAD (2.5 mg/kg) was added on postoperative day 7. Drugs were given orally, and in the combined therapy regimens, administered 6 hours apart. Outcome variables included daily weight, radiographs, and histology. RESULTS: Radiographs on postoperative day 7 showed mild and moderate opacification of the left chest in the cyclosporine monotherapy groups and the untreated control group. Addition of SDZ-RAD to cyclosporine treatment on postoperative day 7 reversed opacification by postoperative days 14 and 21. Monotherapy with microemulsion CsA resulted in mild histological rejection by day 7, which progressed to moderate rejection by day 21. Addition of SDZ-RAD on postoperative day 7 reversed acute rejection, resulting in none or minimal rejection at day 21. CONCLUSIONS: SDZ RAD reverses acute rejection under cyclosporine maintenance therapy in a stringent lung allotransplant model.

Acute Disease↗
PubMed2000

Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries.

BACKGROUND: Conventional gray-scale images of intravascular ultrasound (IVUS) cannot accurately differentiate histologic subtypes of sonolucent coronary plaques with or without a lipid core. METHODS: We analyzed radiofrequency signals obtained in vitro from 24 regions of interest (ROI) of noncalcified (sonolucent) plaques in 10 atherosclerotic coronary artery specimens pressure-fixed by formalin. Radiofrequency signals were sampled with a 30-MHz IVUS catheter and digitized at 500 MHz in 8-bit resolution. The ROIs were histologically categorized into 12 plaques with a lipid core and 12 plaques without it. Integrated backscatter and statistical parameters of the radiofrequency envelope (mean/SD ratio [MSR], skewness, and kurtosis) within the ROI were calculated offline, and their ability to detect a lipid core was compared with visual analysis of the IVUS video images. In the group with lipid cores, percent area of a lipid core in each ROI was measured in a digitized histologic image by a computerized planimeter. RESULTS: Sensitivity and specificity of MSR, skewness, and kurtosis for lipid core detection were substantially greater than visual video image analysis (83.3% and 91.7%, 100% and 91.7%, 100% and 91.7% vs 53.3% and 71.7%). Furthermore, the parameters of integrated backscatter, MSR, skewness, and kurtosis were significantly correlated to percent of core area (r = -0.64, -0.73, 0.78, and 0.63, respectively; P<.05). CONCLUSIONS: Compared with IVUS video images, the parameters of radiofrequency signal analysis may be used to aid in more accurate detection and quantitative evaluation of a lipid core, which is one of the major factors of a vulnerable coronary plaque.

Coronary Artery Disease↗
PubMed2000

Electrophysiological correlates of transmural linear ablation.

The purpose of this study is to describe the characteristics of lesions created using radiofrequency (RF) energy delivered through a saline/foam electrode that is designed to simplify ablation of the isthmus between the tricuspid annulus (TA) and the inferior vena cava (IVC). We compared the changes in the electrophysiological parameters produced by the ablation to histological findings. In search of a more practical and effective atrial flutter ablation method, various energy modifications and catheter designs have been tested. It was shown that the efficiency of RF ablation could be improved using an endocardial cooled catheter; resulting in increased lesion size. Thus, we postulate that a similar advantage of the cooled catheter system would allow efficient RF delivery through specially designed long foam electrodes, therefore improving the practicality of TA-IVC isthmus ablation for atrial flutter. The study was performed in two acute and five subacute sheep under general anesthesia and with adequate heparinization. We used a linear ablation catheter system equipped with two 2-cm saline bipole electrode pockets with 1.5-mm separation, each consisting of two 8-mm electrodes with 1-mm spacing, allowing for bipolar pacing and recording. This saline/foam electrode pair were positioned on a support loop. RF energy was applied to the saline electrodes at 50 watts for 90 seconds with a saline flow rate of 0.4 mL/s. Bipolar atrial signal amplitude and pacing thresholds were measured before and after ablation. If necessary, the catheter was pulled back and additional ablation was applied to any viable tissue. Transisthmus ablations were created with a single catheter positioning in five sheep using both saline electrodes in four and one electrode in the other. Pullback and additional ablation to one saline electrode was required in two sheep; in one after RF was delivered to only one electrode. After ablation, atrial signal amplitude was reduced by an average of 76% (range 51%-92%) and its pacing threshold was increased by an average of 617% (range 150%-400%). Transmural lesions were found in all sheep, measuring 8-20 mm in length, 4-10 mm in width, and 1.5-2.0 mm in depth. No charring, coagulum, or remote structural damage was found in any preparation. Continuous transmural TA-IVC isthmus lesions could be produced with stationary RF linear ablation using a saline/foam electrode catheter system. This system allowed for assessment of electrophysiological parameters that correlated with complete necrosis.

Animals↗
PubMed2000

Dendritic cells and macrophages in lung allografts: A role in chronic rejection?

Antigen presentation by lung macrophages/dendritic cells (DC) is thought to be important in obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS), which severely limits survival post-lung transplantation. However, a recent study found minimal numbers of DC in lung allografts. We looked at numbers and phenotype of macrophages/DC in lung allografts using endobronchial biopsy (EBB) and transbronchial biopsy (TBB) from 22 lung transplant patients. Biopsies were stained with monoclonal markers of DC (CD1a, RFD1, and major histocompatibility complex [MHC] Class II), and "suppressor macrophages" (RFD1 and RFD7). Dendritic cells were also stained for the costimulatory molecules CD80 and CD86. Significantly greater numbers of DC/high-power field (HPF) were seen in biopsies when we defined DC using dendritic morphology and Class II MHC expression instead of CD1a expression. Dendritic cell numbers were significantly higher in eight patients with OB/BOS compared with 14 stable patients. Fifty percent of DC expressed CD86 and 20% expressed CD80. There was no difference in CD80 or CD86 expression between OB/BOS patients and stable patients. There was no correlation between DC numbers and presence or absence of acute rejection (AR), and/or cytomegalovirus (CMV) pneumonitis on current or prior biopsies. There were significantly more MHC Class II DC in EBB compared with TBB. We found minimal staining for lung macrophages capable of suppressing T-cell inflammation. We conclude that studies of lung allografts may underestimate DC numbers if relying on CD1a as the sole marker of DC. DC are increased in patients with OB/BOS compared with stable patients. EBB may be more important than TBB in looking for inflammatory changes of OB. DC expressing costimulatory molecules are present in lung allografts, and costimulatory pathway blockade may be useful in human lung allografts. Also, the absence of "suppressor" macrophages may increase susceptibility of human lung allografts to the rejection process.

Adult↗
PubMed2000

Triptolide attenuates pulmonary arterial hypertension and neointimal formation in rats.

This paper reports the effect of triptolide (a diterpenoid triepoxide) on the development of monocrotaline (MCT)-induced pulmonary hypertension in pneumonectomized rats. Male Sprague- Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Rats received therapy from Day 5 to 35 with triptolide (0.25 mg/kg intraperitoneally, every other day, n = 10), or vehicle (0.1 ml of ethanol/cremophor intraperitoneally, every other day, n = 10). By Day 35, triptolide-treated rats demonstrated lower mean pulmonary arterial pressure (mPAP) than vehicle-treated rats (mPAP 21 +/- 3 versus 42 +/- 5 mm Hg, p < 0.001). Triptolide-treated rats also had significantly less right ventricular hypertrophy (RVH) and pulmonary arterial neointimal formation. In a rescue experiment, rats initiated therapy on Day 21. At Day 35, vehicle-treated rats (n = 4) had higher mPAP (40 +/- 9 mm Hg), greater RVH, and more severe pulmonary arterial neointimal formation than rats that received triptolide (0.25 mg/kg every other day, n = 7, mPAP 30 +/- 4 mm Hg) and rats that received triptolide (0.2 mg/kg daily, n = 7, mPAP 25 +/- 5 mm Hg, p < 0.01). In pneumonectomized rats that receive MCT, triptolide attenuates the development of pulmonary hypertension and RVH, and promotes regression of pulmonary arterial neointimal formation.

Analysis of Variance↗
PubMed2000

Radionuclide imaging of acute lung transplant rejection with annexin V.

STUDY OBJECTIVES: Early detection and treatment of lung transplant rejection is critical for preservation of pulmonary graft function. Damage to pulmonary allografts is mediated by apoptotic cell death induced by the alloreactive T lymphocytes that infiltrate lung grafts. Previous studies demonstrate that acute cardiac allograft rejection can be visualized using radiolabeled annexin V. This study was done to determine whether this technique could visualize acute rejection in a rodent model of unilateral orthotopic lung transplantation. DESIGN: Eighteen Sprague-Dawley ACI rats underwent removal of their left lung followed by orthotopic transplant of either an allogeneic (PVG, immunologically mismatched; N = 10) or a syngeneic (ACI, immunologically matched) pulmonary graft (N = 8). Animals were imaged 1 h after IV injection of 1 mCi (37.0 MBq) of (99m)Tc-annexin V 1 to 7 days after transplantation. RESULTS: Lungs receiving the allograft demonstrated moderate to marked mononuclear infiltration of the perivascular, interstitial, and peribronchial tissues. No mononuclear infiltrates were noted in the native right lungs nor in the syngeneic transplants. Region of interest image analysis revealed significant (p < 0.0005) increases of transplant to normal lung activity ratios 3 to 7 days after allograft surgery. The increased annexin V uptake in these lungs was confirmed at biodistribution assay (allograft 151% greater than isograft activity, p < 0.005). CONCLUSIONS: Acute experimental lung transplant rejection can be noninvasively identified using (99m)Tc-annexin V. Radiolabeled annexin V may be a clinically useful noninvasive screening tool for acute rejection.

Acute Disease↗
PubMed2000

Tissue distribution and clinical monitoring of the novel macrolide immunosuppressant SDZ-RAD and its metabolites in monkey lung transplant recipients: interaction with cyclosporine.

We report the tissue distribution and clinical monitoring of the novel macrolide immunosuppressant SDZ-RAD ¿40-O-(2-hydroxyethyl)-rapamycin and its metabolites in monkey lung transplant recipients as well as its interaction with cyclosporine as the Neoral formulation. After left unilateral lung transplantation, cynomolgus monkeys received by oral administration either 1) 1.5 mg/kg/day SDZ-RAD (n = 4); 2) 100 mg/kg/day cyclosporine (n = 4); 3) 0.3 mg/kg/day SDZ-RAD + 100 mg/kg/day cyclosporine (n = 6); 4) 1.5 mg/kg/day SDZ-RAD + 50 mg/kg/day cyclosporine (n = 5); or 5) SDZ-RAD and cyclosporine doses adjusted according to trough blood concentration measurements (n = 6). At the end of the observation period (usually 29 days after transplantation), and 24 h after the last doses, tissue samples were collected and analyzed with HPLC/mass spectrometry. Gall bladder, pancreas, the transplant lung, cerebellum, kidneys, and spleen had the highest SDZ-RAD concentrations. Coadministration of cyclosporine increased SDZ-RAD concentrations in most tissues as well as tissue-to-blood distribution coefficients. In contrast, SDZ-RAD had only a small effect on cyclosporine blood and tissue concentrations. Rejection in lung grafts in monkeys treated with either of the cyclosporine/SDZ-RAD combinations was significantly less than in the monotherapy groups (P <.002). Histological rejection scores were inversely correlated with SDZ-RAD concentrations in blood (r = -0. 68; P <.001; n = 24), lymph nodes (P = -0.58; P <.003; n = 24), thymus (r = -0.63; P <.001; n = 23) and transplant lung tissue (r = -0.58; P <.003; n = 24). We conclude that, in addition to the synergistic pharmacodynamic interaction, a pharmacokinetic interaction resulting in higher SDZ-RAD tissue concentrations contributed to the significantly better immunosuppressive efficacy when both drugs were combined compared with monotherapy.

Animals↗
PubMed1999

Feasibility of in vivo intravascular ultrasound tissue characterization in the detection of early vascular transplant rejection.

BACKGROUND: Unprocessed ultrasound radiofrequency (RF) signal analysis has been shown to distinguish different tissue structures more reliably than gray-scale interpretation of conventional ultrasound images. METHODS AND RESULTS: The objective of this study was to test the feasibility of in vivo intravascular ultrasound (IVUS) RF signal analysis in an animal model of allograft rejection. Six cynomolgus monkeys underwent transplantation of 3-cm aortic allograft segments distal to the renal arteries from immunologically mismatched donors. IVUS imaging with a 30-MHz system was performed 84 to 105 days after the operation. RF signals were acquired from cross sections of the recipient and the allograft aortas in real time with a digitizer at 500 MHz with 8-bit resolution. Sixty-five cross sections and 68 regions of interest (31 in host aorta and 37 in allograft) were analyzed in the adventitial layer with a total number of 8568 vectors processed. For each region of interest, a weighted-average attenuation was calculated on the basis of the attenuation and length for each individual vector. Histological examination was performed at every cross section imaged by IVUS. When the gray-scale images of conventional IVUS scored by an independent observer were compared, no distinction between adventitia of the native aorta and allograft was possible. Analysis of the average RF backscatter power also showed no significant difference (70.32+/-3.55 versus 70.72+/-3.38 dB). However, the average attenuation of allografts was significantly lower than that of the host aortas (2.64+/-1.38 versus 4.02+/-1.16 dB/mm, P<0.001). Histology demonstrated a marked adventitial inflammatory response in all allografts, with no inflammation observed in the host aortas. CONCLUSIONS: In vivo IVUS tissue characterization can be performed during routine imaging. In this model of transplant vasculopathy, RF attenuation measurements were more sensitive than visual or quantitative gray-scale analysis.

Animals↗
PubMed1999

Mitral annular dilatation and papillary muscle dislocation without mitral regurgitation in sheep.

BACKGROUND: Asymmetrical mitral annular (MA) dilatation and papillary muscle dislocation are implicated in the pathogenesis of functional mitral regurgitation (MR). METHODS AND RESULTS: To determine the mechanism by which annular and papillary muscle geometric alterations result in MR, we implanted radiopaque markers in the left ventricle, mitral annulus, anterior and posterior mitral leaflets, and papillary muscle tips and bases in 2 groups of sheep. One group served as controls (CTL, n=7); an experimental group (EXP, n=9) underwent topical phenol application to obliterate anterior annular and leaflet muscle (confirmed histologically ex vivo). After 1 week of recovery, markers were imaged with biplane videofluoroscopy, and hemodynamic data were recorded. MA area (computed from 3-dimensional marker coordinates) was 11% to 13% larger in the EXP group than in the CTL group (P<0.05 by ANOVA). This area increase resulted exclusively from intercommissural axis increase except in 1 heart with large (>1 cm) increases in both the intercommissural and septolateral annular axes. The anterior papillary muscle tip in EXP was displaced from CTL by 2.9+/-0.23 mm toward the anterolateral left ventricle and 2.5+/-0.12 mm toward the mitral annulus at end systole; the posterior papillary muscle geometry was unchanged. Transthoracic echocardiography revealed MR only in the heart exhibiting biaxial annular enlargement. CONCLUSIONS: MA dilatation in the intercommissural dimension with anterior papillary muscle tip displacement toward the annulus is insufficient to produce MR in sheep. Functional MR may require MA dilatation in the septolateral axis, as observed with proximal circumflex coronary occlusion.

Animals↗
PubMed1999

Coadministration of neoral and the novel rapamycin analog, SDZ RAD, to rat lung allograft recipients: potentiation of immunosuppressive efficacy and improvement of tolerability of staggered versus simultaneous treatment.

BACKGROUND: Neoral and rapamycin derivative (RAD) have complementary mechanisms for inhibition of lymphocyte activation and are substrates for the same pathways of drug metabolism. Therefore, we investigated treatment regimens designed to minimize pharmacokinetic interactions and to potentiate immunosuppressive efficacy in a highly stringent rat lung allograft model. METHODS: Lewis recipients of Brown Norway lungs received the following daily oral doses: (A) RAD at 2.5 mg/kg (n=9); (B) Neoral at 7.5 mg/kg (n=8); (C) RAD at 2.5 mg/kg + Neoral at 7.5 mg/kg simultaneously (n=8); or (D) RAD at 2.5 mg/kg + Neoral at 7.5 mg/kg (n=6) staggered 6 hr apart. Rats were assessed by daily weights, chest radiographs, drug trough levels (high-performance liquid chromatography/mass spectrometry), and blinded scoring of graft histology at death (day 21). RESULTS: Radiographs were completely opacified in all grafts of control and RAD monotherapy groups on days 7 and 14, respectively. Grafts were mildly opacified (Neoral monotherapy) and completely clear (both RAD + Neoral groups) on day 21. Simultaneous or staggered combined treatment dramatically reduced histologic rejection compared with treatment with either drug alone. Simultaneous treatment caused poor tolerability (poor grooming, lethargy) and significantly higher day-14 RAD and cyclosporine (CsA) trough levels (49+/-5 and 638+/-106 ng/ml; P<0.04) than in the staggered group (28+/-3 and 318+/-25 ng/ml) in which all animals were clinically normal. RAD and CsA day-14 trough levels in the staggered group were the same or lower than trough levels in animals treated with either drug alone (RAD 27+/-3/Neoral 815+/-67 ng/ml). CONCLUSIONS: (1) Administration of RAD + Neoral suppressed lung rejection more effectively than treatment with either drug alone. (2) Trough levels did not differ between monotherapy and staggered combination therapy for RAD but were lower for CsA. These results suggested that pharmacological, rather than pharmacokinetic, interactions between the parent drugs were responsible for the potentiation of immunosuppression when these drugs were coadministered. 3) Staggered administration of RAD+Neoral avoided the pharmacokinetic interactions that caused the elevated drug blood levels and poor tolerability caused by simultaneous administration. Thus, we could potentiate efficacy and improve tolerability by staggering administration of RAD and Neoral.

Animals↗
PubMed1999

Potentiation of immunosuppressive efficacy by combining the novel leflunomide analog, HMR 279, with microemulsion cyclosporine in a rat lung transplant model.

BACKGROUND: The novel leflunomide (LFM) analog, HMR 279, potentiates the immunosuppressive efficacy of microemulsion cyclosporine (Neoral) in rodent heart transplantation. The present study was designed to evaluate the immunosuppressive efficacy of this combination in comparison to the combination of Neoral and LFM in a stringent allogeneic rodent lung transplant model. METHODS: Donor lungs from Brown Norway rats were implanted into Lewis recipients and were followed for 21 days. Postoperative monitoring included daily weight assessment, chest radiographs, drug trough levels measured by high-performance liquid chromatography (LFM/HMR 279) and high-performance liquid chromatography/mass spectrometry (Neoral), and blinded histology assessment of the transplanted lung on the day of death based on the International Society for Heart and Lung Transplantation working formulation. Untreated lung recipients served as controls (group I, n=5). Rats were assigned to the following treatment groups: II, 7.5 mg/kg/day Neoral (n=6); III, 10 mg/kg/day LFM (n=6); IV, 10 mg/kg/day HMR 279 (n=6); V, 10 mg/kg/day LFM plus 7.5 mg/kg/day Neoral given simultaneously (n=13); and VI, 10 mg/kg/day HMR 279 plus 7.5 mg/kg/day Neoral given simultaneously (n=6). Drugs were given daily by oral gavage. RESULTS: All rats except for one in the HMR 279 monotherapy group survived the follow-up period. The chest radiographs in the control, LFM, and HMR 279 monotherapy groups showed moderate to complete opacification of the left chest by postoperative day 7 (controls) and day 14 (LFM, 279). At postoperative day 21, the Neoral monotherapy and the combination groups showed no signs of opacification in the radiographs. Combination therapies of Neoral plus HMR 279 or Neoral plus LFM were most successful in preventing histologic allograft rejection. Combining Neoral and HMR 279 resulted in a significant decrease in the cyclosporine trough levels. Co-administration of LFM plus Neoral resulted in significantly higher LFM trough levels when compared to LFM monotherapy. Of all treatments studied, the combination of HMR 279 plus Neoral was tolerated best as assessed by percentage of weight change. CONCLUSIONS: This study showed for the first time in a stringent rodent lung transplant model that combined treatment of LFM or HMR 279 plus Neoral potentiates the immunosuppressive efficacies of these drugs and successfully prevents allograft rejection.

Amides↗
PubMed1999

Constrictive pericarditis due to coccidiomycosis.

Coccidiomycosis is a fungal infection that rarely causes cardiac disease. Constrictive pericarditis in the setting of disseminated coccidiomycosis can be fatal, despite antifungal therapy and pericardiectomy. We report on a patient with constrictive pericarditis due to localized infection by Coccidioides immitis. The patient underwent successful surgical pericardiectomy and antifungal chemotherapy, and remains well 1 year later.

Adult↗
PubMed1999

Quality of computer enhanced totally endoscopic coronary bypass graft anastomosis--comparison to conventional technique.

OBJECTIVE: Aims of the study were to develop an endoscopic technique to perform robot assisted coronary anastomoses, using a computer enhanced telemanipulator and to compare the quality of the anastomoses with those performed using a standard open technique. METHODS: A surgical telemanipulator with two instrument arms and a central videoscopic arm was used to perform remote endoscopic coronary artery bypass grafting on isolated porcine hearts. The end effectors and the videoscope were placed through three 10 mm port incisions. All anastomoses (Cx to LAD) were performed using a double armed 7-0 Prolene suture of 5 or 7 cm in length. All operations were performed remotely from the master console using ten times magnification, tremor filtering and 3:1 motion scaling. Initially 20 anastomoses were performed to develop and train the technique. Then, 20 robot-assisted anastomoses (group I) were compared with 20 anastomoses using a standard open parachute technique (group II). All anastomoses were checked for patency and leakage. Patency was confirmed by bench angiography. After fixation, all anastomoses were macroscopically evaluated for patency, intactness, alignment, intimal tears and dehiscence. Both angiographic and pathologic evaluations were performed with the examiners blinded to the technique of anastomosis. RESULTS: In the initial feasibility series, time for anastomosis was 18.2 +/- 9.1 min. All anastomoses were patent although minor stenoses were found in two and minor leakage was noted in five anastomoses. In the second series all anastomoses were patent, not leaking and showed a good run-off at angiography. Mean time for anastomosis in group I was 12.8 +/- 2.4 min as compared with 6.3 +/- 0.2 min in group II (P < 0.001), respectively. Macroscopic analysis demonstrated equal quality for both groups. There were no stenoses, no intimal tears and no dehiscences. All anastomoses had a normal alignment and intact suture lines. CONCLUSION: Using the Intuitive surgical telemanipulator, it is possible to remotely perform endoscopic coronary anastomoses with the same quality as with an open standard technique after a brief learning curve. This will enable true endoscopic coronary artery bypass grafting with a precision that has not been achieved with any other previously applied endoscopic technique.

Anastomosis, Surgical↗
PubMed1999

Suppression of acute rejection in allogeneic rat lung transplantation: a study of the efficacy and pharmacokinetics of rapamycin derivative (SDZ RAD) used alone and in combination with a microemulsion formulation of cyclosporine.

BACKGROUND: The novel immunosuppressant SDZ RAD, 40-0 (2-hydroxyethyl)rapamycin, is an orally active rapamycin analogue developed for use in combination with cyclosporine (Neoral). The present study was designed to evaluate the efficacy of SDZ RAD, Neoral, or a combination of both drugs for suppression of acute rejection in an allogeneic, unilateral rat lung transplant model. METHODS: Brown-Norway (RT1n) donor lungs were implanted into Lewis (RT1l) recipients that were observed for 21 days. Postoperative evaluation included daily weights, serial chest radiographs, drug trough levels, and histology scores of the transplanted lung on the day of sacrifice. Treatment groups were comprised of rats treated orally with the RAD vehicle as controls (n = 6); SDZ RAD 2.5 mg/kg/day (n = 9); Neoral 7.5 mg/kg/day (n = 8); Neoral 2.5 mg/kg/day (n = 6); SDZ RAD 2.5 mg/kg/day plus Neoral 7.5 mg/kg/day (n = 7); and Neoral 2.5 mg/kg/day plus SDZ RAD 2.5 mg/kg/day (n = 6). RESULTS: The results of this study showed that neither monotherapy with 2.5 mg/kg/day of Neoral, nor 2.5 mg/kg/day of SDZ RAD prevented severe acute rejection in unilateral lung transplant recipients. Furthermore, despite high dose (7.5 mg/kg/day) Neoral treatment, graft histology showed moderate rejection. However, addition of 2.5 mg/kg/day of SDZ RAD to 7.5 mg/kg/day of Neoral completely prevented histologic rejection in four of seven grafts, although the remaining 3 grafts showed minimal rejection. This combination resulted in significantly higher RAD trough levels when compared to SDZ RAD treatment alone. Combining a lower dose of Neoral (2.5 mg/ kg/day) with 2.5 mg/kg/day of SDZ RAD resulted in less weight loss and improved animal health; however, the histology of lung grafts in these rats showed mild rejection. CONCLUSIONS: This is the first study on the efficacy of the novel rapamycin derivative SDZ RAD for the control of acute lung allograft rejection. Results showed that acute unilateral rat lung allograft rejection is refractory to monotherapy with either high dose Neoral or SDZ RAD. The two regimens of combined treatment with Neoral plus SDZ RAD used in these studies produced either minimal rejection and reduced tolerability or mild rejection and better tolerability and showed potentiation of immunosuppression when both drugs were used together. Additional investigation of these two drugs is needed, however, to devise regimens that produce both high immunosuppressive efficacy and good tolerability.

Acute Disease↗