Disposition of a flow-limited drug (lidocaine) and a metabolic capacity-limited drug (theophylline) in liver cirrhosis.

The plasma clearance after oral administration of a completely absorbed drug that is metabolized by the liver depends on its intrinsic clearance. In cirrhosis the bioavailability of a flow-dependent drug increases because of both portosystemic shunting and hepatocyte dysfunction. A drug with a high extraction ratio, lidocaine, and a drug with a low extraction ratio, theophylline, were administered to 27 patients with cirrhosis and 16 control subjects. We found a significant impairment of both theophylline clearance (p less than 0.001) and lidocaine clearance (p less than 0.001) and an increase in the lidocaine peak concentration (p less than 0.001). The three parameters were significantly correlated with each other. The impairment of theophylline metabolism did not correlate with other indexes of disease severity, whereas lidocaine clearance was lower and lidocaine peak level higher in patients with decompensated cirrhosis and evidence of portal hypertension. Thus impairment in lidocaine disposition, which reflects both hepatocyte dysfunction and portosystemic shunting, correlated closer with the severity of liver disease than did theophylline metabolism.

Ticlopidine-theophylline interaction.

Ticlopidine, a new antithrombotic agent, and theophylline, a widely used bronchodilator drug, are both almost completely metabolized in the liver. To evaluate an interaction between these two drugs, we studied theophylline pharmacokinetics before, after 10 days of ticlopidine administration, and 1 month later in 10 healthy volunteers. We found a highly significant increase in the theophylline elimination half-life (P less than 0.001) and a comparable reduction in its total plasma clearance (P less than 0.001) after ticlopidine treatment. Pharmacokinetic parameters returned to initial values within 30 days after ticlopidine withdrawal. Moreover, no changes in theophylline pharmacokinetic parameters were observed 3 months later, before and after 10 days of placebo administration. Our results seem to exclude direct liver toxicity and may suggest a reversible inhibition of the liver metabolic capacity of theophylline.

The reliability of urinary albumin assay by immunonephelometry in the clinical practice. The critical role of medical surveillance on laboratory routine.

Measurement of the urinary albumin excretion rate (UAER) is essential for the early diagnosis and monitoring of diabetic nephropathy; immunonephelometry is a procedure used worldwide for routine screening of diabetic patients. Since we have met with occasional inconsistent values of UAER in serial urine collections, we searched for possible sources of analytic error. To assess the best working conditions of the instrument in use, the stability of urine samples during storage and the need for previous urine centrifugation, we assayed repeatedly the six automatically diluted points of the standard curve (55.6 to 1.7 mg/l), four control samples of human albumin in saline (100 to 1 mg/l) and 24-h urine collections from outpatient diabetic subjects. The last were also assayed with and without previous centrifugation, and both immediately after collection as well as after storage at -20 degrees C for 7, 42, 79, 97, 128 and 161 days. We concluded that: (1) pre-analytic centrifugation of urine samples in unnecessary; (2) the intra-assay coefficient of variation (CV) of the standard curve changed from 2.4% to 9.3% when moving from the highest to the lowest concentration; the inter-assay CV changed from 4.1% to 14.4%, respectively; (3) the intra-assay CV of the control samples (manually prepared) changed from 5.7% to 10.2% and the inter-assay CV from 7.7% to 22.9%; there was a constant and significant (P < 0.01) underestimation (from -9% to -30%) of the obtained values compared with the expected concentrations; (4) a progressive decrease in recovered albumin by multiple freezing and thawing of urine samples did occur, which became significant after 161 days of storage. In the BNA workbook (menu 7.1, assay protocols), a 7-day validity of the reference curve is reported. Moreover, to economize, pre-dilution cuvettes were often recycled in our hospital central laboratory. We observed that: the intra-assay CV for urine samples was 79.4% with recycled cuvettes and stored standard curve, 11.3% with new cuvettes and stored standard curve, 4.9% with both new cuvettes and newly performed standard curve; the inter-assay CV was 32.6%, 10.5% and 6.4%, respectively. These data emphasize, from the laboratory viewpoint, the need for both accurate calibration of BNA and use of native urines; in addition, they stress the importance of careful supervision of laboratory routine and interpreting analytic results in the clinical setting.

Cardiac metastasis of rectal adenocarcinoma. Surgical treatment.

The authors report a case of cardiac metastasis of a rectal adenocarcinoma that infiltrated the right ventricle and partially obstructed its outflow tract. Surgical treatment was performed because of syncopal attacks. The differential diagnosis between organized thrombi and intracardiac tumor is considered.

Coronary artery revascularization without cardiopulmonary bypass.

At the Texas Heart Institute between October 1969 and August 1983, there were 191 single bypass procedures performed without pump oxygenator support. These cases have been divided into two groups: Group I (160 patients) represents the time period from October 1969 through December 1981 and includes our experience with single vessel left anterior descending (LAD) coronary artery bypass without pump oxygenator support; Group II (31 patients) represents the period between January 1982 and August 1983 and includes our initial operative experience in patients with failed percutaneous transluminal coronary angioplasty (PTCA). Of 145 primary operations in Group I patients, 113 were single bypasses to the right coronary artery with a postoperative infarction rate of 3.5% (4/113). Single bypass to the left anterior descending (LAD) coronary artery in 32 patients who underwent operation early in the series was associated with a postoperative infarction rate of 18.7% (6/32) and is no longer performed without pump oxygenator support. Fifteen patients had previous coronary bypass operations and underwent single bypass without pump as a second procedure. Postoperative infarction rate in this redo group was 6.6% (1/15). Long-term follow-up data was obtained on all patients from 1 to 11 years after surgery (mean follow-up, 4 years). Four late cardiac deaths occurred at 2,3,4 and 7 years in the primary operation group (3.5%) 4/113. One late death occurred at 7 years in the redo group (6.6%) 1/15. In Group II, failed PTCA accounted for 39% of the 31 patients who underwent single right bypass without pump support; there were no perioperative infarctions and one death. Coronary bypass can be safely and effectively employed without pump oxygenator support if performed expeditiously and limited to right coronary lesions which have an adequate distal vessel. This technique has become more useful with the advent of attempted PTCA for single coronary lesions.

[Technical variants of median sternotomy]. / Varianti tecniche alla sternotomia mediana

Various modifications of the technique of median sternotomy are described. Advantages thus obtained with respective to saving time and better haemostasis are explained.

[A case of simulation of ovarian cyst in volvulus of an ectopic spleen]. / Un caso di simulazione di cisti ovarica nel volvolo di milza ectopica

A case of volvulus of ectopic spleen mistaken for twisted ovarian cyst is described. Attention is drawn to six points: 1) the rarity of the condition; 2) the persistent uncertainty concerning its aetiopathogenesis, even though over a century has passed since the first case was reported; 3) the mechanism leading to twisting of the spleen stalk; 4) the absence of specific symptoms and the consequent impossibility of preoperative diagnosis in most cases; 5) the ready confusion with ovarian cyst; 6) the reasons for supposing that the reported case was the result of congenital factors.

[Left atrial thrombosis in patients with antiphospholipid antibody syndrome and mesenchymal abnormal septum]. / Trombosi atriale destra in paziente con sindrome da anticorpi antifosfolipidi e setto anomalo mesenchimale.

Antiphospholipid antibodies are a heterogeneous family of immunoglobulins that includes lupus anticoagulant and anticardiolipin antibodies. They are strongly associated with a clinical syndrome characterized by venous and arterial thrombosis and spontaneous fetal losses. This syndrome may be primary or else secondary to autoimmune or neoplastic diseases. The cardiovascular system is frequently involved with mitral or aortic insufficiency, juvenile myocardial infarction, and primitive pulmonary hypertension. However, the occurrence of intracardiac thrombi is rare. We describe a case of an intracardiac right atrial thrombus in a 19-year-old asymptomatic woman who was admitted in December 1998 to the Thrombosis Center owing to the finding, during routine work-up, of a prolonged activated partial thromboplastin time (71 s) and thrombocytopenia (71 x 1000/mm3), a positive antinuclear antibody test (1/320), positivity for lupus anticoagulant, and increased IgG (92 GPL-U/ml) and IgM (27 MPL-U/ml) anticardiolipin antibodies. Six months later, the patient presented with headache, edema and cyanosis of the face and jugular swelling. Transthoracic and transesophageal echocardiography revealed a right atrial mass which was clearly distinguishable from the tricuspid valve and extended to the superior vena cava. The patient was successfully submitted to surgical excision of the thrombus. Histology revealed that the mass was adherent to an abnormal septum consisting of mesenchymal tissue. Although the American Rheumatology Association criteria for the diagnosis of systemic lupus erythematosus were not fulfilled, the positivity of antinuclear antibody test is in favor of a lupus-like syndrome. The decision to opt for surgical excision of the thrombus was determined by the unclear nature of the atrial mass. It may be necessary that such patients be submitted to anticoagulant therapy for the rest of their lives or temporarily (6-12 months). This underscores the importance of the anatomical abnormality as a promoting factor. Transthoracic echocardiography (as well as transesophageal echocardiography in selected cases) must be considered as an essential component of the initial diagnostic work-up in patients presenting with antiphospholipid antibodies.

[Interatrial communications of the ostium secundum type in the adult (author's transl)]. / Le comunicazioni inter-atriali tipo ostium secundum nell'adulto.

On the basis of personal observations made during their first year of activity in cardiac surgery, the authors review the existing literature concerning surgical indications for interatrial communications in the adult. While they recognize that there is a strong correlation between patient age and mortality, they argue that corrective surgery for such defects can be done also in the older patients, with due regard to limiting criteria relative to pulmonary arterial pressure, pulmonary arteriolar resistance, and cardiac failure.

[Cerebral protection in surgery of the carotid arteries]. / La protezione cerebrale in corso di chirurgia della carotide.

The authors, starting from the larger and larger spreading of the carotid surgery, consider the risks of cerebral ischemia involved and the measures suitable to reduce its incidence. So, they analyse the measures, both pharmacologic and mechanical, which, before, during and after operation, may contribute in reducing the possibility of incidence of such a deprecable complication.

[Myocardial protection during open heart operations]. / La protezione miocardica nel corso di interventi a cuore aperto.

The need for adequate protection of the myocardial tissue during open heart operations has proved to be of considerable importance in view of the conditioning value of the functional anatomical state of the myocardial fibre on the outcome of the surgery itself. After a review and description of the most widely used methods of protection, the Authors draw on the data in literature in order to trace a critical profile of each method, outlining its merits and defects in the light of present experience.

[Technical variations in abdominal heterotransplants of the heart]. / Varianti tecniche all'eterotrapianto addominale di cuore.

The Authors describe the innovations by them introduced in a series of 15 experiments of abdominal heart heterotopic transplantation done in the Institute of Veterinary Physiology and Biochemistry University of Milano. Particularly they recommend the use of cardioplegia and the prolene as suture's material to reduce the ischemic time. Also they signal the importance of a new position of the transplanted heart with the apex looking at the head of the recipient. They think this position should be the best to preserve the anatomical connections between the great vessels of the guest heart.