Grade IA Research Articles

Assessment of the myocardial changes in heart transplant recipients without evident acute myocardial rejection by integrated backscatter: comparison with simultaneous dobutamine stress echocardiography and 201thallium spect

Cardiomyocyte hypertrophy and interstitial fibrin deposition develop in cardiac allografts and contribute to the functional changes of transplanted hearts. We hypothesized that integrated backscatter (IBS) can detect these myocardial changes. A total of 32 heart transplant recipients with either no or mild acute rejection (International Society of Heart and Lung Transplantation grade IA) were enrolled in this study. IBS data of myocardium were collected immediately before simultaneous dobutamine stress echocardiography (DSE) and 201thallium imaging. Coronary angiography and endomyocardial biopsy were also performed. Coronary angiography showed diffuse narrowing in 1 patient who also had abnormal results of IBS, DSE, and thallium results. In the other 31 patients with patent coronary arteries, there were 3 patients (10%) with abnormal DSE results, 19 patients (61%) with abnormal IBS patterns, and 16 patients (52%) with reversible thallium perfusion defects. Of the patients, 44% had cardiomyocyte hypertrophy and 56% interstitial fibrin deposition. There were significant differences in the prevalence of 201thallium perfusion defects and serum cyclosporine levels between patients with and without abnormal IBS patterns. Pathologic changes were also associated with abnormal IBS patterns ( p = 0.01). However, there was no association between abnormal IBS and DSE results. By multiple logistic regression analysis, the abnormal IBS patterns were associated inversely with serum cyclosporine level ( p = 0.028). In conclusion, abnormal IBS patterns are associated significantly with perfusion heterogeneity and pathologic changes in heart transplant recipients without evident acute myocardial rejection. There is no association between abnormal IBS patterns and dobutamine-induced dyssynergy in these patients. IBS provides a noninvasive approach for detection of myocardial changes in transplanted hearts without evident acute rejection. (E-mail: porjau@ha.mc.ntu.edu.tw)

Parenchymal liver injury in orthotopic liver transplantation.

A 35-year period of clinical development resulted in orthotopic liver transplantation (OLT) becoming a standardized surgical procedure. Despite this progress, the rate of technical complications is still high. Although the main problem in most analyses is vascular or bile duct failure, we observed a remarkable number of parenchymal liver injuries that led to intraoperative problems. Our aim, therefore, is to present an overall report on the incidence, treatment, and clinical course of parenchymal liver injuries in OLT. Five hundred seventy-two consecutive OLT procedures performed between 1988 and 1998 were analyzed in a retrospective study. Parenchymal liver injury was diagnosed by means of examination of the surgical reports. Donor- and recipient-related data followed the medical report. The lesions were classified according to the Organ Injury Scale. Parenchymal liver injury was diagnosed in 23 patients (4%). The lesions were classified as grade Ia (13.1%), grade Ib (13.1%), grade IIb (52.1%), grade IIIa (17.1%), and grade IIIb (4.3%). In 19 patients (82.6%), the lesion was detected during OLT, and in four patients (17.4%), during relaparotomy. The latter group showed significantly higher-grade injuries. Treatment was suture or fibringlue alone, 17.4%; fibringlue and hemostyptics, 26.1%, mesh wrapping 30.4%, and mesh packing 26.1%. Seven patients (30.4%) underwent relaparotomy. Further active bleeding was not found in any of them. Statistical analysis found a correlation between injury grade and relaparotomy rate. No patients died as a result of parenchymal liver injury. Parenchymal liver injuries can be treated well, with no adverse effect on patient or graft survival. An early decision concerning the surgical procedure for controlling hemorrhage is required. A basically aggressive therapeutic approach might avoid further complications relating to reperfusion edema.

NITRIC OXIDE PRODUCTION IN RENAL TRANSPLANT RECIPIENTS AND iNOS EXPRESSION IN RENAL ALLOGRAFTS

11 Purpose: Nitric oxide (NO) has been reported to be involved in acute allograft rejection process in animal models, and previously also in human. The present study is to investigate kinetics of NO metabolites, as an index of NO production, in recipients after renal transplantation. Furthermore, expression of inducible NO synthase (iNOS) in allografts was examined to investigate a site of NO production. Methods: Serum and urine samples at various points from 21 renal transplant recipients were retrospectively evaluated. The recipients were consisted with 3 groups as follows; Control group: recipients with uneventful clinical course (n=12), AR group: recipients with biopsyproven acute rejection episodes (Grade Ia∼IIa : n=6), ATN group: recipients with ATN episodes (n=3). All patients received cyclosporine or tacrolimus-based immunosuppression. Stable metabolites of NO (NO2− + NO3− = NOx) were measured by Griess method using HPLC. Furthermore, immunohistochemical staining was performed to evaluate expression of iNOS in allograft core-biopsy specimens. Results: In control group, serum levels of NOx significantly decreased after renal transplantation from 50.1±23.7 μmol/L at pre-transplantation to 9.0±4.6 μmol/L at 2 days after transplantation (p<0.05). Thereafter, serum levels of NOx was stabilized at baseline levels between 16 and 20 μmol/L. In AR group, serum levels of NOx significantly increased from 20.4±4.0 μmol/L to 52.8±31.7 μmol/L at 2.1±1.5 (0∼4 days, p<0.05) days prior to the increase of serum levels of creatinine (Cr), and increase up to 82.2±56.4 μmol/L, respectively. Successful anti-rejection therapy showed the significant decrease in serum levels of NOx at 3 to 5 days after anti-rejection therapy was started, while the significant decrease in serum levels of Cr was observed at 6 days or thereafter. Interestingly, in a case of steroid resistant rejection, serum NOx continued to increase until OKT-3 treatment diminished the acute rejection. Serum levels of NOx in ATN group and urinary NOx/Cr ratio in any groups did not reveal a significant change. Immunohistochemical staining of iNOS was observed in large graft-infiltrating cells during severe acute rejection (Grade IIa), which is morphologically consistent with macrophages. Conclusion: These results indicate serum levels of NOx may serve as a sensitive marker to diagnose acute rejection and to judge the response to anti-rejection therapy.

REJECTION PATTERN OF SIMULTANEOUSLY TRANSPLANTED CARDIAC AND SKELETAL MUSCLE IN A RAT MODEL.

408 Purpose: We sought to correlate cardiac and skeletal muscle allograft rejection in a heterotopic heart transplant rat model for the following purposes: 1) to quantitate the degree and severity of skeletal muscle rejection based on the grading system for cardiac muscle rejection, and 2) to assess the feasibility of use of biopsies from simultaneously transplanted skeletal muscle for surveillance of cardiac rejection.Methods: 34 Lewis (RT11) rats underwent simultaneous heterotopic cardiac and cutaneous maximus skeletal muscle transplants. Of those, 7 rats (Group I) received syngenic grafts from Lewis donors with no immunosuppression and served as control. The remaining 25 rats received allografts from Brown Norway (RT1n) donors in two groups: Group II(n=22) received no immunosuppression, and Group III (n=5) received one week of cyclosporine. Non-immunosuppressed rats (Groups I & II) were sacrificed at days 1 through 7 after the transplant whereas immunosuppressed rats (Group III) were sacrificed at 4 weeks. Tissue sections from the grafts were graded for cellular rejection based on the grading system of the Heart Rejection Study Group (International Society for Heart and Lung Transplantation, ISHLT).Results: All group I and III grafts were functional at 7 days post-transplant with no evidence of rejection. Of group II, 2 rats showed no signs of cardiac or skeletal muscle rejection when sacrificed on day 1. All the other rats (n=20) developed graft rejection within one week after the transplant. Cellular rejection correlated grade for grade in 17/20 (85%). Of the three rats that did not show grade to grade correlation, the cardiac biopsy was interpreted as Grade IA in one case when the skeletal muscle showed no rejection. In each of the other two cases, the heart showed focal solitary lymphocytic infiltrate with myocyte replacement (Grade II), and the muscle flap showed diffuse perivascular and interstitial lymphocytic infiltrates without myocyte necrosis (Grade IB). The severity of rejection correlated in 19/20 (95%) rats: mild rejection (Grades IA, IB, II): 9/10 rats (90%); moderate (IIIA, IIIB): 6/6 (100%) and severe (IV): 4/4 (100%).Conclusion: Skeletal muscle rejection may be quantitated using the ISHLT grading system for cardiac muscle rejection. Cardiac and skeletal muscle allografts had similar pattern and severity of rejection with little grade to grade variability. The clinical implications of this correlation for surveillance of cardiac rejection warrants further investigation.

Drying Of Vanilla Pods Using A Greenhouse Effect Solar Dryer

ABSTRACT This paper describes the basic design of the GHE solar dryer and evaluates the performance of the dryer when used to dry vanilla pods. From laboratory test results it was indicated that the average drying time for vanilla pods was between 49 to 53, 5 hrs, for the case of heating augmentation using coal briquette stoves. The total amount of coal briquettes used to produce drying air temperature between 33 C to 65 C and RH of about 34% during day time was 61 kg equivalent to 6.1 kW heating rate and the average electric energy usage of 36.5 kWh, respectively. Quality test results indicated that the dried products were of grade IA of the export quality standard with vaniline content of 2.36%.

Tumoröse Raumforderungen des Beckenskeletts. Eine radiologische Analyse von 234 Fällen

From the material of a bone tumour record file, an attempt was made to determine criteria enabling radiographic prediction of malignancy and tumour entity of lesions of the pelvis. Patients' age, location and radiographic morphology of 234 space-occupying lesions of the pelvis were analysed retrospectively. 62.8% of all lesions were malignant, and the portion of malignant tumours increased with increasing age. While 68.0% of the lesions were found in the ilium, 18.8% in the pubis and 13.2% in ischium, the proportion of benign and malignant lesions did not vary in the different bones. Lesions showing a growth rate according to Lodwick grade IA and to IB were benign in 100% and in 82.0%, respectively. In contrast, tumours of grade II or III were malignant in 89.1% and 88.0% of cases, respectively. By the construction of subgroups by combining the patients' age and growth rate, the prediction of the malignant potential of a lesion increased significantly. The younger the patient, the more aggressively a benign lesion may grow, while the older the patient the slower a malignant tumour may grow. Prediction of the tumour entity is rarely possible.

Scintigraphic detection of early cardiac rejection by iodine 123-labeled monoclonal antibody directed against monomorphic determinant of major histocompatibility complex class II antigens

Although it has been shown that early cardiac rejection can be visualized by radioimmunoscintigraphy targeting major histocompatibility complex class II antigen, the use of antibodies that bind to a polymorphic determinant of class II antigen has certain disadvantages for clinical application. This investigation was designed to examine the feasibility of scintigraphic detection of cardiac allograft rejection by using a monoclonal antibody that reacts with a monomorphic determinant of rat IA antigens. Twenty PVG rats (RT1 c) and five DA rats (RT1 a) underwent heterotopic transplantation with DA hearts. Two of the 20 allografted rats were treated with FK506 (2 mg/kg/day). Seventeen rats were injected intravenously with 80 μCi of iodine 123-labeled monoclonal antibody reactive with a monomorphic determinant of rat major histocompatibility complex class II antigens (Ox6) 16 hours before scintigraphy, and images were compared with those obtained by injection of 123I-labeled monoclonal antibody against a polymorphic determinant of class II antigens (F17-23-6, anti-RT1 a) (n = 8). Background activity was higher in rats injected with Ox6 than in rats injected with F17-23-6. Uptake of labeled Ox6 in the grafts reflected the severity of rejection as determined by histopathologic criteria. Rejecting allografts with lymphocyte infiltration but without myocyte necrosis could be identified by the scintigraphy with use of labeled Ox6. The ratios of radioactivity in the graft to radioactivity in the blood (percent injected dose per gram of tissue) in rats with grade IA and IB rejection (0.56 ± 0.12, n = 4, p < 0.001) and in rats with grade IIIA and IIIB rejection (0.60 ± 0.09, n = 4, p < 0.001) were significantly greater than in rats with nonrejecting grafts (0.24 ± 0.08, n = 9). In conclusion, radioimmune scintigraphy with use of 123I-labeled monoclonal antibody directed against a monomorphic determinant of major histocompatibility complex class II antigen appears to be a sensitive and noninvasive method for detecting cardiac allograft rejection.

Working formulation nomenclature of heart transplant pathology: A retrospective evaluation of 1037 endomyocardial biopsies

Working Formulation (WF) was recently introduced by the International Society for Heart Transplantation to grade acute cellular rejection, as well as additional lesions observed in endomyocardial biopsies (EMBs). The aim of this study was to evaluate the actual advantages of this grading system in terms of feasibility and predictive value. To this purpose, we reclassified 1037 EMBs performed in our heart transplantation units according to the WF. Our results show that multifocal mild rejection (grade IA), when worsening, tends to progress to multifocal moderate (3A), whereas diffuse mild (1B) generally worsens to diffuse moderate (3B), thus following the same focal or diffuse pattern. Unifocal moderate rejection (grade 2) has a peculiar behavior, in that it almost always resolves, though in our units it is treated the same way as is grade 113. Finally, we found a significant relationship between Quilty B effect and chronic rejection. In conclusion, this retrospective study shows that WF is effective in using both qualitative and quantitative criteria and, particularly, in separating focal and diffuse forms of rejection and devoting a distinct grade to unifocal moderate rejection.

Imaging the rejecting heart. In vivo detection of major histocompatibility complex class II antigen induction.

Mice with abdominal heterotopic heart transplants were studied to determine whether scintigraphic detection of an increase in major histocompatibility complex (MHC) class II antigen expression could be used as a noninvasive method for diagnosing early rejection. Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients (n = 18). Two of the 18 allografted mice were treated with cyclosporine (15 mg/kg/day), and two isografted mice served as controls. Each mouse was injected intravenously with 100 microCi of 111In-labeled anti-MHC class II monoclonal antibodies (10-2-16 and 14-4-4S) 24 hours before scintigraphy. After imaging, the mice were killed for tissue counting and histopathology. Radiotracer uptake in the grafts reflected the severity of rejection as determined by histopathological criteria. The percent injected dose per gram of tissue in excised grafts was 4.8 +/- 1.8 (mean +/- SD) for normal grafts (n = 8), 11.1 +/- 9.7 for grafts with grade IA rejection (n = 3, NS), 18.0 +/- 3.8 for grafts with grade IIIA rejection (n = 4, p less than 0.001 versus normal), 18.7 +/- 3.2 for grafts with grade IIIB rejection (n = 3, p less than 0.001 versus normal), and 22.6 +/- 5.4 for grafts with severe rejection (grade IV) (n = 3, p less than 0.001 versus normal). Rejecting allografts with lymphocyte infiltration but without significant myocyte necrosis could be identified by this scintigraphic method. In the BALB/c donor-C57BL/6 (H2b, IE-) recipient combination, rejecting allografts were visualized by 14-4-4S (anti-IEk,d,p,r) antibody but not by 10-2-16 (anti-IAk,r,s,f) antibody. This difference shows that class II antigens induced on donor hearts are solely responsible for the antibody uptake in positive scintigrams of rejecting allografts. We conclude that 111In-labeled anti-MHC class II antigen antibody imaging is a sensitive and noninvasive method for detecting cardiac allograft rejection.

Assessment of the late proliferative phase endometrium by ultrasonography in patients undergoing in-vitro fertilization and embryo transfer (IVF/ET)

This study reports on 330 women aged 29 to 45 years, who underwent 411 cycles of in-vitro fertilization and embryo transfer (IVF/ET). Vaginal sonograms were performed during the late proliferative phase of natural cycles and cycles of controlled ovarian hyperstimulation (COH) with gonadotrophins, to evaluate both the thickness and echogenicity of the endometrium. Findings classified as Grade I; characterized by homogeneous echogenicity of the endometrium, and Grade II; characterized by an outer peripheral layer of dense echogenicity surrounding a central sonolucent area (i.e. a 'halo pattern'). Grades I and II were subclassified on the basis of thickness into A (greater than or equal to 9 mm) and B (less than 9 mm). Grade IIA ('optimal') was associated with a clinical pregnancy rate per embryo transfer of 33% while Grades IA, IB and IIB ('poor') were associated with a rate of only 7%. Women aged 41-45 years experienced a 25% incidence of 'poor' sonographic grades while the incidence in women less than or equal to 40 years of age was 5%. The presence of various uterine pathologies was associated with 'poor' endometrial grades in 86% of cases while only 11% of normal uteri manifested 'poor' grades. 'Optimal' endometrial grades in natural cycles were consistently associated with 'optimal' grades in ensuing cycles of COH (96%). Women with 'poor' endometrial grades in natural cycles improved in 55% of cases during subsequent COH. The results of this study indicate that sonographic assessment of the endometrial lining in the late proliferative phase during both natural and COH cycles is a valuable method for screening and managing IVF/ET candidates.

Results of multidisciplinary limb salvage in 240 consecutive bone sarcomas

From 1979 to 1989, 240 bone sarcomas of limbs were treated by a multidisciplinary limb salvage protocol. The tumors included 112 osteosarcomas, 71 chondrosarcomas, 3 fibrosarcomas, 10 malignant histiocytofibromas, 40 Ewing's sarcomas and 4 other rarer sarcomas. Patients mean age was 28.6 yr (range 4–91 yr). The average tumor size was 13.5 cm (3–43 cm). There were 2 grade IA, 21 IB, 1 IIA, 188 IIB, and 28 III B according to Enneking's classification. Extratumoral en bloc resection was performed in all cases (large in 113, marginal in 121, intrafocal in 6) by the same surgeon. In poor responders to preoperative chemotherapy with Ewing's sarcomas or osteosarcomas, 35 Grays postoperative radiotherapy was administered. Ewing's sarcomas and osteosarcomas received short preoperative and long postoperative chemotherapy. At last follow-up (median 60 months, range 6–120 months), 150 patients were disease-free; 4 were under treatment and had visible disease; 86 had died. Actuarial disease-free survival rate for patients seen with localized previously untreated disease was 83% at 2 yr and 77% at 3 yr. Fifteen local recurrences were observed (6%). Statistical analysis confirmed the poor prognosis factors of visible metastasis, proximal location and large tumor size, and pointed out the major prognostic value of therapeutic factors: the effectiveness of chemotherapy in Ewing's sarcoma and osteosarcomas, and the adequacy of surgery in all cases. Limb salvage can be performed by a well experienced multidisciplinary team in 96% of limb sarcomas without major risk of local recurrence. However, amputation is safer if the surgeon lacks experience.

Smooth vs. Rough

One-hundred and seventy patients (124 augmentations and 46 reconstructions) were followed for 8 post-operative years. Ninety patients received the "standard" smooth silicone mammary prosthesis, and 80 patients received a polyurethane-covered prosthesis. The longest follow-up was 4 years and the shortest was 1 year, with the average just over 2 years. Six types of complications were registered, with three attributed to implant design (wrinkles, draping, capsules) and three to the operator or surgery (infection, hematoma, extrusion). Firm capsule formation was considered a complication only if another intervention (reoperation, closed capsulotomy, etc.) was recommended by the surgeon or requested by the patient. Ninety-six percent of the patients with polyurethane prostheses had a satisfactory (grade II) or better than satisfactory (grade IA or IB) result, whereas 72 percent of the patients with a standard silicone-gel prosthesis achieved a satisfactory (grade II) or better than satisfactory (grade IA or IB) result. Technical details for use of polyurethane prostheses are given, as well as complications inherent to the polyurethane-covered implant.

Morphologic and cell kinetic studies of prostate cancers. Contribution to grading

The combined histologic and cytologic grading of carcinomas of the prostate is not only important in evaluation of prognosis but determines the choice of therapy with knowledge of staging. Tissue biopsies of 2,200 prostatic carcinomas were classified and graded histologically and cytologically. Furthermore, autoradiographic studies were performed on 69 needle biopsies with 3H-thymidine. The cytologic parameters were correlated with cell-kinetic parameters in classification. Several subgroups of degrees of malignancy were found. Grade Ia corresponds to highly differentiated glandular carcinomas by histology and cytology. Grade Ib carcinomas were histologically well but cytologically moderately differentiated. Grade IIa carcinomas are histologically moderately to poorly but cytologically moderately differentiated. Grade IIb carcinomas correspond to poorly differentiated tumors by histological and cytological criteria. Grade III carcinomas are in most cases undifferentiated. This differentiated grading is particularly important for therapeutic consequences in incidental carcinomas. The therapeutic consequences of grade Ia carcinomas are frequent controls and a wait-and-see attitude. Grade Ib and IIa carcinomas must be treated according to their clinical stage by total prostatectomy. Grade IIb and III carcinomas need a palliative treatment by hormones, castration, irradiation or cytostatic drugs.

Intracranial saccular aneurysms--surgical results of 1,000 consecutive cases.

The results of our surgical treatment of 1,000 patients with intracranial saccular aneurysm were analyzed with special consideration for age, site of aneurysm, preoperative condition and operative timing. The results on discharge were as follows: 543 cases, excellent; 186, good; 117, fair; 93, poor; and 61, dead. About three-fourths of the cases except for 23 cases of vertebrobasilar aneurysm showed either excellent or good result. The mortality rate became worse with aging. The results fairly correlated with the preoperative grades by Hunt and Hess (1968), but the cases of Grade Ia were unexpectedly worse. The timing of operation influenced the mortality rate; especially, the cases operated within 3 to 7 days following the last subarachnoid hemorrhage bore poor results. Follow-up studies revealed that excellent and good cases increased and poor cases decreased. The mortality rate for each year decreased annually to 2% in 1975. This improvement may be attributed to the advancement in the operative management with supplementary procedures and in the treatment for cerebral angiospasms and general condition.