The branching angles in computer-generated optimized models of arterial trees.

The structure of a complex arterial tree model is generated on the computer using the newly developed method of "constrained constructive optimization." The model tree is grown step by step, at each stage of development fulfilling invariant boundary conditions for pressures and flows. The development of structure is governed by adopting minimum volume inside the vessels as target function. The resulting model tree is analyzed regarding the relations between branching angles and segment radii. Results show good agreement with morphometric measurements on corrosion casts of human coronary arteries reported in the literature.

Action of endogenous atrial natriuretic peptide in calves with experimental acute central venous congestion and low cardiac output.

STUDY OBJECTIVE: The aim of the study was to investigate plasma concentrations of atrial natriuretic peptide, aldosterone, and renin during experimentally induced acute central venous congestion. DESIGN: Two experimental calf models were used: (1) right heart failure due to pulmonary artery obstruction; (2) inferior vena cava syndrome produced by inferior vena caval obstruction. Hormonal responses and haemodynamic variables were measured over 6 h. SUBJECTS: Experiments were performed on three female "Schwarzbund" calves, age 3 months, weight 92 +/- 8 kg. MEASUREMENTS AND MAIN RESULTS: In the pulmonary artery obstructed group there was an increase of plasma aldosterone from 6.5(SEM 1.6) to 22.1(3.2) ng.dl-1 (p less than 0.05), of renin from 0.7(0.1) to 2.5(0.3) Goldblatt units x 10(-4).ml-1 (p less than 0.05), and of atrial natriuretic peptide from 22.1(4.5) to 141.4(27.8) pmol.litre-1 (p less than 0.05). During inferior vena caval obstruction, aldosterone increased from 2.4(0.4) to 20.9(2.0) ng.dl-1 (p less than 0.05), and renin increased from 0.4(0.05) to 2.0(0.20) Goldblatt units x 10(-4).ml-1 (p less than 0.05). In this experiment, atrial natriuretic peptide remained unchanged. Cardiac output decreased in both groups. There was significant fluid and electrolyte retention during both experiments, with urine volume decreasing from 87.7(11.6) to 35.0(1.2) ml-h-1 in experiment (1), and from 185(14) to 95.7(8.6) ml.h-1 in experiment (2). CONCLUSIONS: The study suggests (1) that in an experimental acute state of reduced cardiac output due to pulmonary artery stenosis with constantly increased right heart pressures, raised endogenous atrial natriuretic peptide failed to induce diuresis and natriuresis; (2) that in acute right heart failure, renin and aldosterone secretion could not be suppressed by raised atrial natriuretic peptide concentrations; and (3) atrial natriuretic peptide secretion seemed to be exhausted after 6 h continuous atrial distension.

The progression of mild acute cardiac rejection evaluated by risk factor analysis. The impact of maintenance steroids and serum creatinine.

The natural course of mild acute cardiac allograft rejection (MAR) under cyclosporine-based therapy is generally considered benign, and usually antirejection therapy is not instituted. The present study was undertaken to determine the frequency of and the risk factors for progression of MAR into a clinically significant (moderate or severe) rejection on subsequent endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from 3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs. Depending upon the outcome on the subsequent EMB, MAR was categorized as progressive or nonprogressive. This served as the dependent variable for a stepwise logistic regression analysis evaluating 11 covariates as potential risk factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy, underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P less than 0.0001). Stepwise logistic regression yielded the type of maintenance therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615) as independent predictors of progression of MAR. After adjustment for influence of maintenance therapy and serum creatinine none of the cyclosporine variables provided any additional information. MARs without maintenance steroids and low serum creatinine levels had the highest risk (37.2% observed incidence) to develop moderate or severe rejection on subsequent EMB. This analysis supports evidence that diagnosis of MAR on EMB is associated with a considerable high progression rate into clinically significant rejection when compared to negative EMBs. Progression particularly occurs in MAR under steroid-free maintenance therapy and suggests early augmentation of immunosuppression. In terms of progression of MAR serum creatinine values, obviously indicating cyclosporine nephrotoxicity, appear to reflect the extent of cyclosporine-mediated immunosuppressive activity more properly than parameters of its bioavailability by measuring cyclosporine HPLC blood levels.

Independent risk factors predicting acute graft rejection in cardiac transplant recipients treated by triple drug immunosuppression.

To assess independent risk factors predicting the occurrence of clinically significant acute rejection episodes in the first 6 months after cardiac transplantation, we performed a multivariate stepwise logistic regression analysis. Forty-three recipients, undergoing transplantation between September 1986 and May 1988, were eligible for analysis and received standardized, low-dose triple drug maintenance immunosuppression with cyclosporine, azathioprine, and prednisolone. Immunoprophylaxis was supplemented perioperatively with either a polyclonal (antithymocyte globulin, N = 26) or a monoclonal (OKT3, N = 17) anti-T-cell antibody. Investigated, conceivable risk factors comprised recipient and donor age, ischemic time, perioperative anti-T-cell antibody prophylaxis, recipient preoperative status, underlying disease, previous cardiac operation, and histocompatibility parameter (mismatches for HLA-A, HLA-B, HLA-DR, HLA-B+DR, HLA-A+B+DR, and Rh0[D] antigen, HLA-DRw6 positive recipient, and identify for ABO system). Univariate analysis suggested significant influence of the type of antibody used perioperatively (p = 0.0024) and the number of mismatches for HLA-A+B+DR (p = 0.0037) and for HLA-B+DR (p = 0.0043). Stepwise logistic regression yielded the number of mismatches for HLA-B+DR (p = 0.0029) and the type of antibody used perioperatively (p = 0.0031) as being highly significant predictors of acute cardiac rejection. Six-month freedom from rejection was 100%, 41%, and 27% for recipients with two, three, and four mismatches for HLA-B+DR and 59% versus 22% for recipients with polyclonal versus monoclonal antibody prophylaxis. Similar to results with kidney transplantation, these results indicate that a poor donor/recipient match for combined HLA-B+DR loci constitutes an independent risk factor for acute graft rejection in low-dose triple drug immunosuppressed cardiac recipients, which stimulates the potential concept of prospective HLA matching. In our experience OKT3 prophylaxis provides significantly less effective prevention of acute rejection than a comparable course of antithymocyte globulin.

Inducible atrial flutter and fibrillation after orthotopic heart transplantation.

Inducible atrial flutter (two patients) and fibrillation (two patients) were observed in a series of 35 heart transplant patients who underwent evaluation of sinus node function including premature atrial stimulation. The sinus node function was entirely normal in both patients with inducible atrial flutter. In contrast it was profoundly abnormal in the patients with inducible atrial fibrillation. Atrial fibrillation was no longer inducible as the sinus node function became borderline normal. These observations suggest extensive electrical atrial abnormality, including the sinus node, in patients with atrial fibrillation, and temporary pacing should be available when considering cardioversion in patients with atrial fibrillation early after heart transplantation. Atrial flutter, in contrast, may be inducible in the absence of any sinus node abnormality and without any evidence of rejection.

Pseudopericardial effusions in heart transplant recipients.

BACKGROUND: The objective of this study was to determine the nature of sonographically observed band-shaped, homogeneous, almost echo-free structures located ventral to the right ventricle of the heart in heart transplant recipients. METHODS: A total of 212 consecutive heart transplant recipients was evaluated sonographically. RESULTS: In 18 of the 212 patients (8.5%) band-shaped structures were detected, and these structures were proved with computed tomography or magnetic resonance imaging to be caused by mediastinal fat. CONCLUSIONS: A sonographically demonstrable, almost echo-free band-shaped structure located ventral to the heart should not be misinterpreted as localized pericardial effusion.

TATI (tumor associated trypsin inhibitor) and cancer antigen 125 (CA 125) in patients with early-stage endometrial cancer.

BACKGROUND: In patients with gynecologic malignancies, a 6 kD polypeptide known as the tumor-associated trypsin inhibitor (TATI) is present in high concentrations, both in the urine and the serum. This study attempts to evaluate the usefulness of pretreatment serum levels of TATI (cutoff level 21 ng ml-1) and CA 125 (cutoff levels 35 U ml-1 and 65 U ml-1) in the prediction of early endometrial cancer. PATIENTS AND METHODS: One hundred twenty-seven patients with stage I and II endometrial carcinomas, 110 healthy women and 258 women with benign pelvic pathologies were evaluated. The data obtained were correlated with the tumor stage and tumor grade. RESULTS: Overall, TATI showed a sensitivity of 31% and a specificity of 81%. The sensitivity and specificity of CA 125 > 35 U ml-1 was 25% and 86%, respectively. When both serum tumor markers were combined the sensitivity increased to 48% (CA 125 > 35 U ml-1), with a specificity of 71%. A correlation with the depth of myometrial infiltration was found for neither of the tumor markers under investigation. In addition, neither TATI nor CA 125 correlated well with tumor grade. The combination of TATI and CA 125 had a high positive predictive value (84%) when no other gynecologic pathologies were present. Furthermore, if TATI and CA 125 levels are within normal ranges and gynecological examination does not show other abnormalities besides vaginal bleeding, endometrial carcinoma appears to be very unlikely. CONCLUSION: We concluded that, while TATI and CA 125 may not be recommended as a screening method for the detection of endometrial cancer, the combination of TATI and CA 125 is a valuable additional tool for further evaluation of women with suspected uterine cancer.

The application of fibrin glue after axillary lymphadenectomy in the surgical treatment of human breast cancer.

Experimental studies point out that a reduction of lymph flow can be obtained by the local application of fibrin glue following axillary lymphadenectomy in the surgical treatment of breast cancer. In a prospective study the influence of human fibrin glue on postoperative axillary lymph secretion and the period of drainage of the wound cavity were evaluated. In 40 patients, 5 ml of fibrin glue (Tissucol) was applied to the wound cavity by the use of a spray applicator (Tissumat) immediately after axillary dissection of the lymph nodes. For drainage of the wound area Redon suction-drains were used. The daily amount of postoperative lymph secretion was measured and drains were removed at a lymph secretion of less than 20 ml. 40 patients who underwent surgery and axillary lymphadenectomy without subsequent application of fibrin glue sourced as control group. No significant difference concerning the total amount of lymph secretion, the mean period of drainage or the incidence of lymphatic cysts was observed. In our study, the expected occlusion of the wound cavity by the application of fibrin glue after axillary lymphadenectomy did not lead to any advantage when compared with the control group.

Influence of delayed diagnosis on established prognostic factors in endometrial cancer.

To evaluate the influence of delayed diagnosis on prognostic factors in endometrial cancer, we conducted a retrospective chart analysis based on the data of 116 postmenopausal patients with FIGO stage I-IV endometrial carcinoma. The interval from the first episode of post-menopausal vaginal bleeding to definitive, histological diagnosis (bleeding interval) was compared with tumor stage and various histomorphologic features in endometrial cancer. The mean bleeding interval was 12.7 +/- 17.8 weeks in 74 patients with FIGO stage IA, IB endometrial carcinoma and 35.2 +/- 69.3 weeks in 42 patients with stage IC-IV disease (t-test, p: 0.011). FIGO stage IA, IB disease was diagnosed in 23/26 (88%) patients with a bleeding interval <4 weeks, and in 22/34 (64%) and 29/56 (51%) patients with bleeding intervals of 4-8 weeks and >8 weeks, respectively (Chi-square 10.358, p=0.006). The correlation with histologic grade, lymph-node status, vessel invasion and histologic subtypes did not reach statistical significance. Our data confirm the clinical impression that postmenopausal vaginal bleeding is an early symptom in patients with endometrial cancer, and that advanced disease in the majority of cases might come from delayed diagnosis in women with poor compliance.

Computer-optimization of vascular trees.

Arterial branchings closely fulfill several "bifurcation rules" which are deemed to optimize blood flow. The question is whether these local criteria in conjunction with a general optimization principle can explain the overall structure of an arterial tree. We present a model of an arterial vascular tree which is grown on the computer by successively adding terminal vessel segments. Each new terminal segment is connected to the optimum site within the preexisting tree, and the new bifurcation is optimized geometrically. After each step of adding and optimizing, the whole tree is rescaled to meet invariant boundary conditions of pressure and flow at each terminal site. Thus, local geometric optimization is used to induce simultaneously an optimized global structure. The comparison between the model and real coronary arterial trees shows good agreement regarding structural appearance, morphometric parameters, and pressure profiles.

The histopathologic identification of CMV infected cells in biopsies of human renal allografts. An evaluation of 100 transplant biopsies by in situ hybridization.

In order to determine the incidence and significance of CMV infected cells within human renal allograft biopsies 100 transplant biopsies were examined for the presence of CMV DNA within the renal tissue specimens using the in situ hybridization technique. In 41 cases CMV infected cells were predominantly found within proximal tubular epithelial cells, although typical nuclear inclusion ("owl eyes") were absent. In only one case was CMV detected within a few glomerular cells. The presence of CMV infected cells within allograft biopsies does not correlate with active CMV infection of the patients at the time of biopsy. There are no significant differences in the distribution of primary and secondary CMV infections between patients with positive and negative biopsy findings. No significant differences as to the histological alterations between CMV infected and non-infected biopsies could be found. The data give evidence that the renal allograft is more often affected by CMV than is generally appreciated. The in situ hybridization technique may be useful for the fast detection of latently CMV infected cells in renal transplants and thus may influence the choice of therapeutic steps early after transplantation. Furthermore, it may facilitate the diagnosis of interstitial nephritis due to virus infection if typical nuclear inclusions in routinely stained tissue sections are absent.

Hystero-salpingo scintigraphy: a routine investigation in sterile women?

Based on the spontaneous migration of radioactive tracer from the posterior vaginal fornix to the ovaries and peritoneal cavity, several attempts were made to assess hystero-salpingo scintigraphy (HSS). The low acceptance rate by sterile women of routine investigation of tubal function may be due to a fear of radiation exposure and unpleasant examination procedures. Our protocol for HSS adopts a low dose of radioactive tracer (0.2-0.3 mCi), a defined mode of application (between the external and internal os of the cervical canal) and a short imaging time (60 min). From 1990 to 1992, we investigated 60 fallopian tubes in 32 sterile women by HSS, hystero-salpingography (HSG) and/or chromopertubation during laparoscopy (LPSC). The results of HSG and HSS corresponded in 15 of 49 fallopian tubes, LPSC and HSS in 9 of 24. None of the 32 patients had become pregnant naturally during the average observation period of 17 months. Two patients became pregnant after in-vitro fertilization. HSS, performed according to our protocol, causes less pain and results in a lower dose of radiation than HSG (about 50%). It is well accepted by patients and is easy to perform. As an investigation of tubal function, HSS may serve as an additional examination technique in cases of presumed tubal sterility.

[Heart transplantation in childhood]. / Herztransplantation im Kindesalter.

This report presents 5 children, in whom a heart transplantation was performed at the II. Chirurgische Universitätsklinik of Vienna. At the time of transplantation the age of the children was 2, 3, 6, 10, and 14 years. The preoperative diagnosis was dilative cardiomyopathy in two patients, hypertrophic cardiomyopathy, right ventricular decompensation after atrial repair of TGA and a tumor of the heart in the other patients. Three children are alive and well. One child suffered from severe postoperative complications and 1 child died because of rejection of the heart. Indication, follow-up, complications of the therapy and the position of heart transplantation in children are discussed.

Neuron specific enolase demonstration in the diagnosis of a solid-cystic (papillary cystic) tumour of the pancreas.

Immunoreactivity to neuron specific enolase (NSE) was demonstrated in a solid-cystic (papillary cystic) tumour of the human pancreas, employing immunohistochemical methods. Positive staining for NSE was found with two different antisera. In addition, sodium-dodecyl-sulphate-polyacrylamide-gel-electro-phoresis (SDS-PAGE) of tumour homogenate revealed a distinct band reacting with a NSE antiserum. However, we failed to detect any hormonal products or neuroendocrine granules in the tumour. Therefore the authors advise caution in using the enzyme as a differential diagnostic tool, especially in surgical pathology of epithelial pancreatic neoplasms occurring in young females. In individual cases electron microscopy will be necessary since solid-cystic tumours of the pancreas consistently show large intracytoplasmic zymogen-like granules.

Pathology of renal cancer and its metastases.

The pretherapeutic classification of renal carcinomas includes the assessment of the tumor stage, the histological gross pattern, the cytological features, and the histopathological grading. As to the local tumor extension the perinephric invasion and renal vein involvement are the most important prognostic features. The presence of metastases dramatically alters survival. Histologically, compact, tubular, and papillary growth patterns are differentiated. Furthermore, the verification of the cell types in renal carcinomas is of prognostic significance. The clear cell carcinomas are opposed to the granular cell and spindle-shaped/pleomorphic types with poor prognosis. Rarely tumors consist of so-called "chromophobe" cells with finely reticular cytoplasms. They closely resemble clear cell carcinomas and exhibit a similar biological behaviour. According to the grade of atypia in renal carcinomas three grades of malignancy are distinguished. Conclusively, the tumor grade and the tumor cell type are the most reliable indicators of the malignant potential of renal carcinomas.