Precision and long-term stability of different estradiol immunoassays assessed in a multi-center quality control study.

BACKGROUND: Because of the vast range of physiological relevant estradiol concentrations the requirements to be met by an estradiol assay are high. In the present study the performance of various commercially available estradiol assays was evaluated with regard to imprecision and long-term stability. METHODS: Precision and long-term stability of 7 commercially available estradiol immunoassays were assessed in a multi-centre quality control study based on the repeated measurement of liquid BIOREF estradiol control sera by 18 laboratories during a 14-month study period. RESULTS: The mean estradiol concentrations determined in 594 runs performed for each control level were 71 pg/ml, 349 pg/ml and 676 pg/ml. A high variation was found for the method specific mean values calculated from all results measured with the same method, which ranged between 32 - 90 pg/ml, 187 - 392 pg/ml and 373 - 790 pg/ml, resulting in a similar high inter-laboratory variation with coefficients of variation (CVs) of 25.0%, 16.7% and 17.5%. In contrast, the intra-laboratory variation of estradiol values as well as the variation of values measured with the same method were found to be considerably lower with coefficients of variation < 10% for most laboratories and methods; only the low control level was measured with CV values > 10% by the majority of laboratories and methods. For none of the laboratories a tendency was observed in the results from beginning to end of the 14 month study period indicating a high uniformity in assay production and a good long-term stability of the control material used. CONCLUSIONS: The present data demonstrate that also with the currently available estradiol immunoassays the comparability of results measured with different methods is limited. With most assays very low estradiol concentrations, as observed in postmenopausal women, can be determined only with a precision which is not adequate for clinical assessment.

Prosthetic replacement for the thoracic vena cava: an experimental study.

The superior vena cava (SVC) and thoracic inferior vena cava (IVC) were replaced in 46 dogs with autologous vein, knitted Dacron, glutaraldehyde-fixed porcine pericardium, unsupported polytetrafluorethylene (PTFE), and externally stented PTFE. After 30 days, patency rates were determined by contrast venography and were 100%, 9%, 50%, 75%, and 100%, respectively. The patency rates of Dacron and glutaraldehyde-fixed pericardium are considered unacceptable when compared to autologous vein (p less than 0.05). Stented PTFE exhibited a patency rate equal to that of autologous vein at 30 days, minimal graft reaction, excellent incorporation by host fibroblasts, and a smooth neointima. The external spiral support added to PTFE enchanced the thromboresistance of this graft in the thoracic venous system. Long-term follow-up is required to determine if the stented PTFE prosthesis remains comparable to autologous vein as a venous conduit.

Early experience with homograft aortic root replacement for complex aortic pathology.

BACKGROUND: Complex aortic valve and root pathology presents a serious operative challenge. METHODS: During the last 45 months 21 cryopreserved homograft root replacements have been performed in 19 patients. The ages of the patients ranged from 28 to 77 years; there were 15 men and four women. Six patients had endocarditis, four prosthetic and two native valve endocarditis. One patient underwent homograft aortic root replacement twice; one underwent concomitant homograft right ventricular outflow tract reconstruction for pulmonic endocarditis. Causes of aortic pathology in the other 13 patients included ascending aortic aneurysm with valvular regurgitation in seven, Marfan syndrome in two, and four aortic dissections with aortic regurgitation. Ten of the nineteen patients were undergoing reoperative procedures. RESULTS: There were three hospital deaths and one death at home of unknown cause. Two of the three patients who died in hospital had undergone redo cardiac procedures. Dramatic functional class improvement was seen in all survivors. CONCLUSIONS: Follow-up from 2 to 45 months in the fifteen survivors revealed no clinical or significant echocardiographic evidence of valvular regurgitation or recurrent infection. We believe homograft root replacement provides an excellent method of reconstruction with several advantages unique to human valved conduits, including ease of handling, lack of synthetic nidus for recurrent infection, and absence of thrombogenic materials. Homografts should be considered the approach of choice in complex valvular and root infectious processes.

Intraluminal shunting of operatively severed aortocoronary saphenous vein grafts.

Restoration of myocardial perfusion using plastic shunts in severed aortocoronary bypass grafts is described.

Prevention of pericardial adhesions with dextran 70.

Pericardial adhesions pose a major problem during reoperative cardiac surgical procedures. The purpose of this study was to determine the effect of intrapericardial dextran 70 on the formation of pericardial adhesions in an animal model. The data obtained revealed that intrapericardial dextran 70 reduced the incidence of experimental pericardial adhesions.

Factors contributing to recurrent carotid disease following carotid endarterectomy.

BACKGROUND: Retrospective analysis was performed to assess the effect of gender, age, hypertension, diabetes, and smoking upon residual disease, recurrent disease, and progression of disease following carotid endarterectomy (CE). The effect of patch versus primary closure was also studied. METHODS: Postoperative duplex studies were performed following 323 CEs at months 1, 6, 12, and 24. Residual disease was defined as luminal stenosis >59% at 1 month. Progression of disease was defined as stenosis at any month that was greater than stenosis at month 1. Recurrent disease was nonresidual stenosis >79%. RESULTS: Correlation was found between age at operation <65 years and cigarette smoking; both also correlated with progression of disease on serial studies, as well as recurrent stenosis <79%. Primary closure of the arteriotomy correlated with residual disease. CONCLUSION: Primary closure of the arteriotomy following CE increases the likelihood of residual disease. Smokers and those aged <65 years are predisposed to progression of postoperative disease, and to development of recurrent stenosis.

Acute repair of a full-thickness right ventricular defect with a composite myofascial pedicle flap.

A full-thickness defect of the right ventricle presented acutely after mediastinitis and sternal dehiscence. This developed 29 days after bilateral internal mammary artery harvest for coronary artery bypass grafting. The defect was managed successfully with a pedicled left rectus abdominis muscle flap using an attached island of the anterior rectus sheath for endocardial lining. The vascular anatomic basis for viability of the rectus abdominis muscle flap after internal mammary artery harvest is derived primarily from musculophrenic, lumbar, lower sixth intercostal, and subcostal artery communications. In addition, the advantages of a myofascial pedicle flap for reconstruction of full-thickness cardiac defects are its ready availability and a strong anterior fascial sheath that can be used as a neoendocardial lining. The patient did well and remains asymptomatic after 3 years.

Allograft replacement of the aortic valve for active endocarditis.

PURPOSE: In the 50 months preceding March 1995, 35 adult patients underwent aortic valve replacement with a cryopreserved human aortic valve allograft. Nine of these patients had active endocarditis. The remaining 26 patients had aortic valve pathology without active infection. This study consists of a comparison of these two groups. METHODS: One of the patients with active infection underwent inclusion technique replacement of the infected valve. The other eight valves were replaced with root-replacement technique. Of the 26 non-infected patients, 4 valves were replaced with the inclusion technique, and the remaining 22 were replaced with the root-replacement technique. None of the patients are maintained on long-term anti-coagulation. RESULTS: We have followed the infected group an average of 32 months and the group without active infection has been followed an average of 27 months. There were two perioperative deaths in the nine patients with infected valves and no deaths in the group without active infection (Pearson's chi2 p<0.05). There have been no thromboembolic complications and no recurrent infections.

Prophylaxis of heart transplant rejection with either antithymocyte globulin-, Minnesota antilymphocyte globulin-, or an OKT3-based protocol.

We compared an equine antithymocyte globulin (ATGAM)-based protocol with a Minnesota antilymphocyte globulin (MALG)-based protocol and a murine monoclonal CD-3 (OKT-)-based protocol in 3 groups of heart transplant (HT) recipients. Thirty-four recipients received a four-day course of ATGAM. Thirty HT recipients received a 14-day course of OKT3. Fifteen HT recipients received MALG for an average of 10 days. The ATGAM group received cyclosporine beginning preoperatively, while the OKT3 and MALG groups received CyA beginning on post-transplant day 4. All three groups received identical azathioprine and similar steroid therapy. The 3 groups were similar in age, donor/recipient HLA mismatches, and donor/recipient gender mismatches. The MALG and OKT3 groups had 20% and 17% females, respectively, while the ATG group had 41% (p < 0.05). Average follow-up exceeded 14 months for each group. The ATGAM group received a higher dose of CyA during "induction" therapy than the OKT3 and MALG groups, and experienced a greater rise in post-transplant serum creatinine levels. We found no difference between the 3 groups in: preoperative creatinine levels, one-year post-transplant creatinine levels, number of patients who could be successfully "weaned" from steroids, or one-year survival. Other data are tabulated as episodes/patient: [table: see text] We conclude that ATG plus preoperative CyA is superior for rejection prophylaxis following heart transplantation when compared with either MALG plus postoperative CyA or OKT3 plus postoperative CyA.

Clinical heparin coated cardiopulmonary bypass: reduction of systemic heparin requirements for redo cardiac surgery.

The authors compared blood loss, transfusion requirements, and heparin doses for reoperative cardiac surgery using either: a) a Duraflow (Baxter Corporation, Irvine, CA) heparin coated cardiopulmonary bypass (CPB) system or b) standard CPB. Twenty patients underwent redo cardiac surgery while supported with heparin coated CPB, and 17 patients underwent redo cardiac surgery with standard CPB. The following data are presented as mean +/- standard deviation. The heparin coated CPB circuit group received significantly less heparin than the standard CPB group (322 +/- 80 IU/kg versus 448 +/- 80 IU/kg, p < 0.01). There was no difference in blood loss in the first 24 postoperative hrs or mean transfusion requirements for the two groups. Despite the reduced dose of heparin, the mean activated clotting time in the heparin coated group was similar to the mean activated clotting time of the standard CPB group (577 +/- 98 sec versus 612 +/- 117 sec, p = ns). In conclusion, heparin coated CPB without reduced activated clotting time does not reduce transfusion requirements or blood loss in reoperative cardiac surgery. The heparin coated CPB system allows maintenance of the activated clotting time level despite reduced heparin doses.

[Modification of the risk profile of obese essential hypertensive patients by the group "hypertension discussion" program]. / Beeinflussung des Risikoprofils von adipösen essentiellen Hypertonikern durch das Gruppenprogramm "Hypertonie im Gespräch".

The programme "Discussions on Hypertension" is a programme for group treatment of obese essential hypertensives in medical practices on the basis of behavioural therapy. A co-operation model was developed between the Department for General Medicine of the "Medizinische Hochschule Hannover", the Institute for Medical Psychology of the "Philipps-Universität Marburg" and the company Galenus Mannheim and was offered to doctors in general practice. The effects of the programme on the modifying of the risk profile for coronary heart disease was investigated in a controlled study in 137 patients by nine general practitioners. 81 patients were enrolled in the experimental group and 56 patients were assigned to a control group that was not using the programme. The experimental and control groups were comparable with respect to sociodemographic, psychological and medical parameters. Three months after completing the programme, the results of the study was shown in specific effect both on the psychological criteria of success (well-being, health knowledge, healthy behaviour, salt use and compliance) and in a reduction of the diastolic blood pressure in spite of a reduction of the antihypertensive drug treatment. The blood lipid levels (cholesterol and triglycerides) and the blood glucose level were also favourably affected. Patients in the experimental group had reduced their weight by an average of 5.6 kg. The patients in the control group only by 0.8 kg. Overall, there was a marked reduction in the proportion of patients with several risk factors in the experimental group, so that the programme can be attributed a preventive effect.

Individual reference ranges of CA 15-3, MCA and CEA in recurrence of breast cancer.

The long-term intra-individual variation of the title tumour markers was studied in the group of 33 patients which developed no relapse. The average biological intra-individual CV was 11.2% for CA 15-3 and 14.9% for MCA whereas those of CEA strongly depended on the concentration. The intra-individual standard deviation of CEA was independent of concentration and amounted to 0.23 g/L. Individual reference ranges the analytes were much smaller than the group reference ranges. Individual reference limits were calculated on the basis of the average intra-individual variation. In 21 of the 22 patients who developed recurrence during the follow-up period, individual reference limits of CA 15-3 and/or CEA were exceeded 1 to 31 months (median 10 months) before clinical evidence (diagnostic sensitivity 95%). Group reference limits were exceeded only in 13 patients (diagnostic sensitivity 60%) and occurring later. The diagnostic specificity was 97%. MCA did not provide additional information. The combination of CA 15-3 and CEA is an excellent for detection and exclusion of recurrence in the follow-up of breast cancer patients if decision-making is based on individual reference limits. Improvement of the long-term analytical quality of the tumour marker assays, particularly in the low concentration range is necessary.

Extraesophageal manifestations of gastroesophageal reflux disease.

Gastroesophageal reflux is frequently viewed as a "nuisance" problem that affects a large number of individuals with variable frequency. When physicians conceptualize the complications of gastrointestinal reflux, they generally consider them a localized esophageal problem resulting in irritation of the esophagus, bleeding esophagitis, occasional stricture formation, and the development of Barrett's esophagus. However, attention has again been focused on the potential relationship between gastroesophageal reflux and pulmonary diseases (cough, asthma, recurrent pneumonia), chest pain, and hypopharyngeal or oral disease. This paper reviews our current understanding of the extraesophageal manifestations of gastroesophageal reflux.

Intra-individual variation of serum thyroxin and triiodothyronine in pregnancy.

The mean concentrations of triiodothyronine (T3) and thyroxin (T4) in serum were increased in pregnancy, the increases for individuals remaining stable for week 16 to week 40 of gestation. For this period biological intra-individual variations of T3 and T4 in serum were estimated and compared with those of non-pregnant women. The average biological intra-individual CVs for T3 and T4 were of the same order for pregnant and non-pregnant women (6.9-8.4%). The ratios of the biological intra-individual CVs to the biological group CVs were 0.5 to 0.6. Individual values were normally distributed. There was no increase of the intra-individual variation with the lapse of time between two consecutively observed values. The estimated average biological intra-individual CVs were used to derive decision-making criteria in monitoring thyroid function during the 2nd and 3rd trimester of gestation.

Intraesophageal balloon distention versus drug provocation in the evaluation of noncardiac chest pain.

Intraesophageal balloon distention (IEBD) has been advocated as an effective provocative test for the evaluation of chest pain and dysphagia. The normal esophageal response to intraesophageal balloon distention is to generate a sustained contraction proximal to the balloon while showing a distinctive absence of activity distal to the balloon. We evaluated intraesophageal balloon distention in 62 patients with noncardiac chest pain and compared the diagnostic results to those obtained by using a combination of acid infusion, edrophonium (80 micrograms/kg iv) and bethanechol (80 micrograms/kg sq). These 62 patients were also compared with 10 normal volunteers who underwent intraesophageal balloon distention. Abnormal distal manometric activity consistent with spasm and was seen in 38/62 (61%) patients. Distal manometric activity was not seen in any normal volunteer. Diagnostic results (symptom reproduction with manometric changes but without EKG changes) were seen in 26/62 (42%) patients, but in nine of the 62 (14%) patients with combined drug provocation (p less than 0.05). Intraesophageal balloon distention is superior to a combination of provocative drugs in evaluating noncardiac chest pain symptoms. The presence of abnormal manometric activity distal to the balloon may represent regulation of esophageal motility.

Prospective evaluation of high-dose bethanechol in investigation of esophageal chest pain.

We compared the value of bethanechol 80 micrograms/kg subcutaneously, acid infusion with a 0.1 normal hydrochloric acid, and edrophonium 80 micrograms/kg intravenously as provocative agents to reproduce chest pain and manometric alterations in 72 patients with noncardiac chest pain. No patient developed typical chest pain and manometric alteration with acid infusion, while five (6.9%) patients developed these changes with edrophonium and four (5.6%) with bethanechol. Only one patient developed diagnostic changes exclusively with bethanechol. All patients tested with bethanechol developed some degree of local pain or significant cholinergic symptoms, with two patients requiring atropine for relief. Side effects from edrophonium were infrequent (28% of patients tested) and did not require atropine administration. We conclude that, using the parameters of typical chest pain and the development of manometric alterations as proof of the esophageal origin of chest pain, bethanechol at 80 micrograms/kg adds little information beyond that obtainable with edrophonium. Further, the high incidence of bethanechol-related side effects at 80 micrograms/kg suggests that this dose should not be generally recommended.

Intraesophageal balloon distention in the manometric evaluation of chest pain.

Drug provocation is routinely used during esophageal manometry in the evaluation of chest pain of presumed esophageal origin. As significant side effects have been associated with the use of drugs in provocation, and these provocative tests are inadequately sensitive to exclude esophageal etiology as the cause of chest pain, alternative provocative tests have been sought. Intraesophageal balloon distention (IEBD) has recently been reintroduced as a method of pain provocation in the manometric evaluation of chest pain. IEBD produces pain on distention which resolves immediately on deflation. To evaluate graded IEBD as an effective and safe method of pain provocation, 66 consecutive patients presenting with chest pain and 10 asymptomatic volunteers were studied. We conclude that balloon distention is an effective and safe method of pain provocation and can easily be performed in conjunction with standard esophageal manometry.

Manometric responses to balloon distention in patients with nonobstructive dysphagia.

The manometric responses to graded intraesophageal balloon distention were studied in 30 patients with symptoms of intermittent dysphagia but without evidence of structural narrowing on barium swallow or endoscopy, or both. These studies were compared with those performed in 10 normal volunteers. Using a manometric catheter with a balloon of reproducible dimension, balloon distention produced a sustained pressure proximal to the distended esophageal balloon in 28 of 30 (93%) patients and 9 of 10 (90%) normal volunteers. Patients with dysphagia had the reproduction of their characteristic symptom during balloon distention in 23 of 30 (76%) cases. Atypical symptoms not characteristic of the patients' usual dysphagia developed in the other 4 patients with dysphagia and in all controls. There were no electrocardiographic changes during balloon distention and symptoms were immediately reversible with balloon deflation. Repeated simultaneous contractions consistent with spasm distal to the distending esophageal balloon occurred in 21 of 30 (70%) patients with dysphagia but in no normal volunteers (p less than 0.05). Dysphagia reproduction was associated with the finding of repeated simultaneous contractions distal to the intraesophageal balloon being found in 20 of 30 (66%) patients (p less than 0.05). Distal activity during balloon distention of the esophagus is associated with dysphagia reproduction in a significant number of patients without any other explanation for their symptom. The development of distal spasm in patients with intermittent dysphagia suggests an abnormality of neural control that may be important in the pathophysiology of dysphagia in these patients.