Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy.

Childhood dilated cardiomyopathy (DCM) is a leading cause of heart failure requiring cardiac transplantation and approximately 5% of cases result in sudden death. Knowledge of the underlying genetic cause can aid prognostication and clinical management and enables accurate recurrence risk counselling for the family. Here we used genomic sequencing to identify the causative genetic variant(s) in families with children affected by severe DCM. In an international collaborative effort facilitated by GeneMatcher, biallelic variants in PPP1R13L were identified in seven children with severe DCM from five unrelated families following exome or genome sequencing and inheritance-based variant filtering. PPP1R13L encodes inhibitor of apoptosis-stimulating protein of p53 protein (iASPP). In addition to roles in apoptosis, iASPP acts as a regulator of desmosomes and has been implicated in inflammatory pathways. DCM presented early (mean: 2 years 10 months; range: 3 months-9 years) and was progressive, resulting in death (n = 3) or transplant (n = 3), with one child currently awaiting transplant. Genomic sequencing technologies are valuable for the identification of novel and emerging candidate genes. Biallelic variants in PPP1R13L were previously reported in a single consanguineous family with paediatric DCM. The identification here of a further five families now provides sufficient evidence to support a robust gene-disease association between PPP1R13L and severe paediatric DCM. The PPP1R13L gene should be included in panel-based genetic testing for paediatric DCM.

Pathologic interpretation of transbronchial biopsy for acute rejection of lung allograft is highly variable.

Despite the standardization of pathologic grading of acute rejection in transbronchial lung biopsies following lung transplantation, the reproducibility of pathologic diagnosis has not been adequately evaluated. To determine the interobserver variability for pathologic grading of acute rejection, 1566 biopsies from 845 subjects in the Lung Allograft Rejection Gene Expression Observational study were regraded by a pathology panel blinded to the original diagnosis and compared to the grade of acute rejection assigned by individual center pathologists. The study panel confirmed 49.1% of center pathologists' A0 grades, but upgraded 5.7% to A1 and 2.7% to grade ≥ A2 rejection; 42.5% were regraded as AX. Of 268 grade A1 samples, 21.2% were confirmed by the pathology panel; 18.7% were upgraded to ≥ A2 and 35.8% were downgraded to A0 with 24.3% being regraded as AX. Lastly, 53.5% of ≥ A2 cases were confirmed, but 15.7% were downgraded to grade A0 and 18.4% cases to A1, while 12.4% were regraded as AX. The kappa value for interobserver agreement was 0.183 (95%CI 0.147-0.220, p < 0.001). The results for B grade interpretation were similar. Suboptimal sampling is common and a high degree of variability exists in the pathologic interpretation of acute rejection in transbronchial biopsies.

Characterization of anti-HLA class II monoclonal antibody LGII-612.14 reacting with formalin fixed tissues.

mAb LGII-612.14 derived from a BALB/c mouse immunized with interferon-gamma (IFN-gamma) treated cultured human B lymphoid cells LG-2 has been shown with serological and immunochemical assays to recognize a monomorphic determinant expressed on the beta chain of HLA-DR, -DQ and -DP antigens. The linear nature of the determinant, which is likely to be formed by residues 19-25, is indicated by the reactivity of mAb LGII-612.14 with HLA-DR, -DQ and -DP beta chains purified by electrophoresis in presence of SDS. An unusual characteristic of mAb LGII-612.14 is its reactivity with fixed tissue sections. The intensity of staining is affected by the incubation temperature, the incubation time and the fixative used. Maximal intensity of staining of formalin fixed, paraffin embedded tissue sections required an incubation time of 16 h. The intensity of staining of paraffin embedded tissues initially fixed with Bouin's solution, formalin or ethanol was similar to that of frozen tissue sections and stronger than that of tissues fixed with B5 solution. No staining was detected of paraffin embedded tissues fixed with glutaraldehyde or Zenker's solution. Comparison of the staining patterns with mAb LGII-612.14 of frozen and fixed tissue sections showed that the latter substrates provide a superior detail of tissue architecture and cellular morphology without significant loss of sensitivity. Furthermore, comparison of the characteristics of mAb LGII-612.14 with the few previously published anti-HLA class II mAb reacting with fixed tissues indicates that mAb LGII-612.14 stains formalin fixed, paraffin embedded tissues, while mAb 910D7 and TAL-1B5 stain tissues fixed with less commonly used fixatives. Furthermore, mAb LGII-612.14 is likely to yield more sensitive staining results than anti-HLA-DR, -DQ and -DP mAb KUL/05. The present results indicate that mAb LGII-612.14 represents a useful probe to apply immunohistochemical techniques to the analysis of the distribution of HLA class II antigens in fixed tissues. This will greatly facilitate the use of readily available collections of fixed tissue specimens in retrospective studies to assess the clinical significance of changes in HLA class II antigen expression which occur in various disease states.

Prolongation of primate cardiac xenograft survival with cyclosporine.

Cardiac xenotransplantation in nonprimates using traditional immunosuppression (azathioprine and prednisone) or cyclosporine has been unsuccessful or has required doses of immunosuppressants not tolerated by man. This study sought to determine if primate hearts could be transplanted successfully across genus boundaries using a dose of cyclosporine applicable to human transplantation. The hearts of outbred cynomolgus monkeys (Macaca fascicularis) were heterotopically transplanted into the necks of outbred baboons (Papio anubis). Hyperacute rejection did not occur and there were no cyclosporine-induced malignancies or nephrotoxicity. A 12-fold prolongation of mean cardiac xenograft survival to 77 days was accomplished using parenteral cyclosporine and steroids. The histology of rejection was notable for the appearance of reversible rejection on the 30-day biopsies. The histopathologic and immunologic data support the role of both cell-mediated and humoral mechanisms in primate cardiac xenograft rejection. Neither mixed lymphocyte cultures or cytotoxic antibody assays were predictive of graft loss, but there was a significant increase in their respective levels at the time of cessation of graft function. Thus, significant prolongation of primate cardiac graft survival across a genus boundary was accomplished using a dose of cyclosporine similar to that used in human transplantation.

Short course single agent therapy with an LFA-3-IgG1 fusion protein prolongs primate cardiac allograft survival.

The interaction of T cell costimulatory molecules with their ligands is required for optimal T cell activation. Interference with such interactions can induce antigen unresponsiveness and delay xeno- and allograft rejection. We have previously shown that LFA3TIP, a soluble human lymphocyte function-associated antigen (LFA)-3 construct, binds CD2 and inhibits responses of human T cells in vitro. This study reports the first use of a human fusion protein, LFA3TIP, to significantly prolong primate cardiac allograft survival. Based on our observations that LFA3TIP inhibits baboon allogeneic mixed lymphocyte reactions, we gave baboon recipients of heterotopic cardiac allografts injections of LFA3TIP, 3 mg/kg i.v., for 12 consecutive days, starting 2 days before transplantation. This regimen delayed graft rejection from an average of 10.6 +/- 2.3 days for human IgG-treated controls (n = 5) to an average of 18.0 +/- 5.3 days for LFA3TIP-injected animals (n = 7; P < or = 0.01). Grafts from LFA3TIP-treated animals showed markedly diminished coronary endothelialitis as compared with control animals. LFA3TIP reached peak serum levels of approximately 100 micrograms/ml after 7-9 injections and persisted in the 10-micrograms/ml range for 1 to 2 weeks after the final injection. Despite these blood levels, circulating antibodies to LFA3TIP were not detected in the serum. No renal or hepatic toxicity was noted. The possible mechanism by which LFA3TIP acts to inhibit graft rejection is discussed; success in prolonging graft survival when LFA3TIP is used as a single-agent therapy suggests great potential for this novel therapeutic agent.

Monoclonal antibody identification of mononuclear cells in endomyocardial biopsy specimens from a patient with rheumatic carditis.

A 17-year-old woman with rheumatic carditis underwent endomyocardial biopsy both prior to and following treatment with prednisone and aspirin. Frozen sections from the endomyocardial biopsy specimens were studied with monoclonal antibodies by an indirect immunofluorescence technique to define the composition of the inflammatory infiltrate in the myocardium and to determine whether the composition of the infiltrate is distinctive and diagnostically useful. The specimen from the initial biopsy contained a heterogeneous infiltrate composed of T lymphocytes, macrophages, B lymphocytes, and mast cells. T lymphocytes predominated, and the ratio of T-helper to T-cytotoxic/suppressor cells was 2.0. Following treatment the overall cellularity of the infiltrate was diminished, but the infiltrate remained heterogeneous; T cells predominated, and the T-helper to T-cytotoxic/suppressor ratio was reversed, to 0.59. The composition of the inflammatory infiltrate in this case of rheumatic carditis distinguishes it immunologically from other "idiopathic," presumably virus-associated, forms of myocarditis.

Adhesion molecules (E-selectin and ICAM-1) in pulmonary allograft rejection.

Vascular endothelial cells act as antigen-presenting cells in the lung allograft and stimulate alloreactive host lymphocytes. Activated lymphocytes and cytokines can induce expression of leukocyte-endothelial adhesion molecules that facilitate invasion of the allograft by circulating leukocytes. To define the role of endothelial HLA class II antigen and adhesion molecule expression in lung allograft rejection, we prospectively analyzed endothelial expression of HLA class II, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) antigens in 52 transbronchial biopsy specimens from 24 lung allograft recipients as compared to normal control subjects. Thirty-one of 52 specimens showed histologic rejection and 8 of 24 patients developed histologic obliterative bronchiolitis (OB) by the end of the study period. Increased expression of HLA class II antigen was seen in 32 of 52 (62%) lung allograft specimens, but increased expression did not correlate with acute rejection or OB. In contrast, E-selectin expression was seen in 30 of 52 (58%) biopsy specimens and was associated with acute rejection (p < 0.005) and with the development of OB (p < 0.05). Increased expression of ICAM-1 was seen in only 18 of 52 (35%) biopsy specimens and did not correlate with acute rejection or OB. These data suggest that E-selectin expression may be a tissue marker of acute and chronic lung rejection possibly by promoting leukocyte adhesion to the allograft endothelium. The high levels of endothelial HLA class II expression may reflect long-term antigenic stimulation of the allograft even in the absence of rejection.

Long-term function of human cardiac allografts assessed by two-dimensional echocardiography.

Previous studies from our laboratory demonstrated increasing left ventricular mass in cyclosporine-treated cardiac allograft recipients over 30 days after transplantation, but the long-term evolution of this process and possible effects on allograft function are unknown. Accordingly, quantitative two-dimensional echocardiography was performed 2 and 23 days and 15 months postoperatively in 14 recipients treated with cyclosporine and prednisone. Changes in left ventricular ejection fraction, end-diastolic volume, mass, and end-systolic wall stress were analyzed. Comparison of studies at 2 and 23 days revealed significant (p less than 0.01) increases in ejection fraction (54% +/- 8% [standard deviation] to 62% +/- 4%), end-diastolic volume (84% +/- 32 ml to 96 +/- 31 ml), and left ventricular mass (118 +/- 45 gm to 136 +/- 41 gm). Comparison of studies at 23 days and 15 months revealed no significant change in end-diastolic volume or left ventricular mass, whereas ejection fraction decreased slightly (62% +/- 4% to 57% +/- 4%, p less than 0.01). End-systolic wall stress decreased when data at 2 days and 15 months were compared (83 +/- 24 gm/cm2 versus 66 +/- 18 gm/cm2, p less than 0.05), but no change in contractility was apparent from the ejection fraction/end-systolic stress relation. We conclude that left ventricular mass and end-diastolic volume increase early after transplantation in cyclosporine-treated cardiac allograft recipients, but these changes are not predictive of long-term results, which are characterized by no significant late variation in left ventricular mass, end-diastolic volume, or contractility.

Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection.

BACKGROUND: Cyclosporine-based immunosuppressive regimens (INN: ciclosporin) in human lung transplantation continue to result in a high incidence of acute cellular rejection. We investigated the use of sirolimus, a macrolide with structural similarity to tacrolimus, as monotherapy and in combination with cyclosporine in a rodent lung transplant model. METHODS: Orthotopic left lung transplantation was performed in Lewis recipients from Brown-Norway donor rats with syngeneic Lewis-to-Lewis controls. Open biopsies were performed on postoperative day 7, and the severity of acute lung rejection was graded by a pathologist blinded to the protocol. RESULTS: All recipients survived despite the amount of acute rejection seen on examination of the biopsy tissue. Lewis-to-Lewis isografts demonstrated near normal pulmonary architecture. Allogeneic recipients receiving high-dose cyclosporine (25 mg/kg) monotherapy showed mild to moderate acute rejection with some perivascular focal interstitial infiltrates. Recipients receiving low-dose cyclosporine (5 mg/kg) monotherapy or low- or high-dose sirolimus (0.5 or 2.0 mg/kg, respectively) monotherapy demonstrated massive cellular infiltration leading to necrosis and infarction and could not be graded. However, the addition of low-dose sirolimus (0.5 mg/kg) to low-dose cyclosporine (5 mg/kg) demonstrated a significant potentiating immunosuppressive effect, and the addition of high-dose sirolimus (2.0 mg/kg) to low-dose cyclosporine (5.0 mg/kg) demonstrated an even greater effect, with rejection scores better than those obtained with high-dose cyclosporine monotherapy and similar to those obtained with isografts. CONCLUSIONS: This study demonstrates that low-dose sirolimus has a cyclosporine-sparing effect and that a higher dose of sirolimus in combination with cyclosporine strongly protects lung allografts from acute cellular rejection. These results suggest that sirolimus may be indicated as an adjunct to current cyclosporine-based immunosuppressive regimens in clinical lung transplantation.

University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial.

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.

Vascular (humoral) rejection in human cardiac allograft biopsies: relation to circulating anti-HLA antibodies.

Vascular or humoral rejection (as defined by linear deposits of immunoglobulin and complement in myocardial capillaries) and the presence of circulating lymphocytotoxic anti-HLA antibodies are each associated with reduced long-term graft or patient survival. The relationship between these two factors has not been determined. We used immunofluorescent techniques to study 46 cardiac biopsy specimens in 16 patients from 15 to 412 days after transplantation. Biopsy specimens were selected from the first 2 months, and at approximately 6 and 12 months after transplantation and did not include episodes of acute cellular rejection. Each specimen studied was compared to a serum sample drawn an average of 1.8 days (range, 0 to 9 days) from the time of biopsy to assay for circulating anti-HLA antibodies. Of the specimens obtained at or near a positive anti-HLA antibody test, 90% (27 of 30) were found to have linear deposits of immunoglobulin (not necessarily with complement) versus 75% (12 of 16) of specimens obtained at the time of a negative test. Twenty-one cases of vascular rejection were documented. Both immunoglobulin M and immunoglobulin G were deposited along with complement in 13 instances; immunoglobulin M and complement were deposited in eight cases; no case had only immunoglobulin G and complement. The presence of circulating anti-HLA antibody in the serum was associated with 14 of the 21 cases of vascular rejection. Linear deposits of immunoglobulin in the capillaries of myocardium were frequently observed when anti-HLA antibodies were present in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Photochemotherapy in human heart transplant recipients at high risk for fatal rejection.

Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk.

Binding of preformed xenoantibodies to porcine bioprosthetic valves.

We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials.

Prevention of acute regional ischemia with endocardial laser channels.

Laser myocardial revascularization has been shown to reduce mortality and infarct size after left anterior descending coronary artery (LAD) ligation in dogs. It has not been shown to improve myocardial contractility in acute ischemia. In this study a holmium-yttrium-aluminum garnet laser (wavelength, 2.14 microns) was used to create nontransmural myocardial channels from the endocardial surface in the ischemic regions of the canine left ventricle. Twelve mongrel dogs (6 controls, 6 laser myocardial revascularizations) underwent 90 minutes of LAD ligation followed by 6 hours of reperfusion. The ischemic region was determined by methylene blue injection during brief LAD occlusion. Laser myocardial revascularization averaged three channels per square centimeter in the ischemic region created using 12 J/channel (600 mJ/pulse, 10 Hz) before LAD ligation. Contractility was assessed from regional preload recruitable stroke work (RPRSW), using pairs of segment length ultrasonic transducers in the ischemic and the nonischemic regions. Two-dimensional echocardiography corroborated with segmental length findings. In control dogs, the ischemic region was dyskinetic during LAD ligation and reperfusion. Dyskinesis of the ischemic region during systole produced negative values for regional stroke work, and RPRSW was considered zero. In 4 of 6 laser-revascularized dogs, RPRSW remained positive in the ischemic region. Two dogs had intermittent dyskinesis. The difference between laser-revascularized and control dogs in ischemic region RPRSW was significant (p < 0.01 by Fischer's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent intravenous leiomyomatosis with cardiac extension.

A case of recurrent intravenous leiomyomatosis with cardiac extension and a temporally extended presentation is described. Complete excision was achieved employing simultaneous sternotomy and laparotomy and deep hypothermia with circulatory arrest. Coronary revascularization was performed concomitantly with complete tumor resection. Diagnostic, operative, and pathologic considerations are reviewed and a preferred surgical approach discussed.

Normal bronchial healing without bronchial wrapping in canine lung transplantation.

The deleterious effect of steroids on bronchial healing in lung transplantation has led to the development of techniques to protect the anastomosis and to the exclusion of steroid-dependent patients from transplantation. The effect of steroids on bronchial healing was tested in a canine single-lung allotransplantation model. Twenty size-matched mongrel dogs (20 to 30 kg) underwent left lung transplantation without anastomotic wrap or direct revascularization. Postoperatively, all received daily doses of cyclosporine (15 mg/kg) and azathioprine (1 mg/kg) and were subdivided into three steroid dosage groups. Group A (n = 10) animals received 1.5 mg/kg of prednisone per day whereas groups B (n = 5) and C (n = 5) received 5.0 mg/kg of prednisone per day for 28 postoperative days. In addition, group C received prednisone (5.0 mg.kg-1.day-1) for 1 month preoperatively. In group A, 8 of 10 dogs survived 28 days without evidence of respiratory compromise, with anastomotic bursting pressure greater than 510 mm Hg. In group B, all 5 dogs survived to 28 days without evidence of respiratory compromise and with intact bronchial anastomoses (bursting pressures greater than 510 mm Hg). In group C, 3 of 5 animals survived to 28 days with intact anastomoses. Histological examination demonstrated normal bronchial healing in all anastomoses. These data suggest that preoperative steroid dependence should not be a contraindication to lung transplantation and that bronchial anastomotic wrapping with vascular tissue may not be essential.

Talc pleurodesis: talc slurry versus thoracoscopic talc insufflation in a porcine model.

BACKGROUND: Pleurodesis using both talc slurry and thoracoscopic talc insufflation has been shown to be clinically effective. This study compares these two modalities of pleural talc instillation in an animal model. METHODS: Eleven immature pigs underwent general endotracheal anesthesia. On one side, a slurry of 5 g sterile United States Pharmacopeia talc in 50 mL of saline solution was instilled through a thoracostomy tube. On the other side, the lung was deflated and 5 g of dry talc was insufflated under thoracoscopic visualization. The animals were sacrificed 30 days later, and the quality of pleural adhesions was graded from 0 to 2 (0 = absent; 1 = light; 2 = dense) in each of six regions of each hemithorax. The distribution of adhesions on each side was graded from 0 to 6, according to the number of areas that contained adhesions. RESULTS: One animal died of anesthetic complications. Among the survivors, adhesions produced by both methods were dense and diffuse in 8 of 10 animals, and light and diffuse in 1 animal. One animal had light or absent adhesions on the talc slurry side, and dense and diffuse adhesions on the thoracoscopic talc insufflation side. There was no difference between the techniques for density of adhesion scores (talc slurry, 9.9 +/- 2.2; thoracoscopic talc insufflation, 10.0 +/- 2.5) or distribution of adhesion scores (talc slurry, 5.5 +/- 1.0; thoracoscopic talc insufflation, 5.8 +/- 0.4) (p > 0.1). CONCLUSIONS: Effective pleurodesis in a porcine model can be obtained with either talc slurry or thoracoscopic talc insufflation.

Testicular biopsy and occult tumor in acute lymphocytic leukemia.

Testicular biopsy has become a routine procedure before discontinuing chemotherapy in male children being treated for acute lymphocytic leukemia (ALL). Before a decision can be made to discontinue multiple drug therapy, all possible sites of occult tumor such as the testis, cerebrospinal fluid, and bone marrow must be sampled. Between December, 1978, and November, 1981, 25 male children underwent testicular biopsies after two or more years of combination chemotherapy at the Babies Hospital, Columbia-Presbyterian Medical Center. Only 3 of the 25 patients (12%) were found to have leukemic infiltrates on histologic sections. Two of 3 patients, however, were noted preoperatively to have either irregular testicular contours or testicular enlargement and induration. Occult testicular infiltration discovered after two or more years of chemotherapy is rare. Most children with a histologically positive biopsy result were at least suspected preoperatively to have testicular involvement.

Intravascular ultrasound imaging of human cerebral arteries.

The aim of this study was to assess the feasibility of imaging cerebral arteries in vitro with intravascular ultrasound and to establish a correlation between echographic images and corresponding histological architecture. Intravascular ultrasound imaging was performed using a 30-MHz, 4.3F ultrasound probe. Twenty-two arterial segments were obtained at autopsy from 6 patients and were imaged fresh. Arteries were then processed for histological examination and comparisons were made between echographic and histological findings. The correlation between luminal area measurements as determined histologically and by intravascular ultrasound was tested by linear regression analysis. Intravascular ultrasound demonstrated a three-layered appearance in normal cerebral arteries but not in those affected by severe atherosclerosis. Overall, ultrasound correctly identified the presence of a plaque in 83% of patients. Intravascular ultrasound sensitivity and specificity, respectively, were 100 and 80% for calcium deposits and 83 and 75% for fibrous tissue. Intravascular ultrasound and histological measurements correlated well for the determination of luminal area (r = 0.89). Intravascular ultrasound provides accurate characterization of the arterial lumen and geometry, as well as the presence and histological features of atherosclerotic plaque. Thus, it appears to have a great potential for an earlier and more accurate diagnosis of atherosclerosis and may serve to guide new interventional techniques being utilized in the treatment of cerebrovascular diseases.