Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.     

Total-body protein turnover in parenterally fed neonates: effects of energy source studied by using [15N]glycine and [1-13C]leucine

The effects of nonprotein energy source (ie, glucose only vs glucose and lipid) on nitrogen retention and total-body protein turnover were studied in 20 parenterally fed newborn infants. All infants received approximately 3 g amino acids and 80-90 kcal.kg body wt.d. Total-body protein synthesis was estimated by using three constant-infusion, end-product methods: enrichment of urinary urea and ammonia in response to a [15N]glycine label and exhaled carbon dioxide enrichment in response to a [1-13C]leucine label. No differences were seen in nitrogen retention between the two energy sources. The estimate of total-body protein turnover obtained from the 13C label was similar to that obtained with the [15N]urea label. No differences in turnover rates were observed between the two diet groups. Use of the glucose-plus-lipid fuel system enhanced energy storage and the reutilization of amino acid for protein synthesis.     

Retained pacemaker leads

Increasingly, functionless pacemaker leads are being abandoned in place because they cannot be safely removed. One hundred eighty-nine intact or partially removed pacemaker leads were abandoned in situ in 152 patients between Jan. 1, 1965, and Dec. 31, 1985. The leads, sometimes several leads in a single patient, were deemed uninfected at the time of abandonment in 137 patients and contaminated with Staphylococcus epidermidis in 15 patients. All of the contaminated leads have remained clinically uninfected during follow-up. One clean lead became infected early after implantation and the patient died after an open cardiac operation to remove that lead and an adjacent abandoned lead that was adherent to the subclavian vein. No other patient has had a late complication during follow-up to 256 months (mean 47.6). Properly managed abandonment of an uninfected lead can carry a very low complication rate.     

Studies of the induction and maintenance of long-term graft acceptance by treatment with FK506 in heterotopic cardiac allotransplantation in rats

Immunosuppressive activities of the newly discovered FK506, isolated from Streptomyces tsukubaensis, were examined by using cardiac allotransplantation in the rat, and the mechanisms underlying induction and maintenance of FK506-induced long-term allograft survival were studied. Male rats of WKA (RT1k) and F344 (RT1lvl) strains were used as recipients and donors, respectively, and those of BN (RT1n) strain were used as third-party donors. Treatment with FK506, beginning from the day of allografting for 14, 10, or as few as 4 days, prolonged allograft survival significantly across the major histocompatibility barrier. The minimum doses for prolonging graft survival were 0.1 mg/kg/day by intramuscular treatment and 1.0 mg/kg/day by oral treatment. Treatment with FK506 at a dose of 0.32 mg/kg/day from day 4 until day 10 resulted in all the grafts surviving indefinitely and from days 5 to 10, half the grafts survived indefinitely, suggesting that the agent inhibited ongoing rejection. On the other hand, cyclosporine treatment at a dose of 20 mg/kg/day from day 2 did not prolong graft survival time statistically significantly. Induction of prolonged graft survival was not obtained by pretreatment of the prospective donor or recipient; prolonging effects were observed only when the agent was administered after allografting. Thus, the primary effect of the agent is exerted on responder lymphocytes reacting to the donor antigens in the induction phase of long-term graft acceptance. The mechanisms underlying the maintenance of long-term grafts were analyzed by testing the capacity of lymphocytes or serum of long-term graft-bearing rats to inhibit graft rejection in irradiated grafted hosts. Transfer of 2 x 10(8) lymphocytes from FK506-induced long-term F344 graft-bearing WKA rats resulted in indefinite survival of F344 heart allografts, but it did not prolong survival of third-party BN hearts. Transfer of 2.5 ml serum from long-term graft-bearing rats also prolonged graft survival of F344 hearts, but not BN hearts. These results suggest that donor strain-specific suppressor cells and humoral factor(s) are induced by treatment with FK506 in the presence of allografts, and that they play at least partial roles in the maintenance of long-term allograft acceptance.     

Cervico-arthrotic myelopathies. Treatment and prognosis

The authors present 50 cases of cervical spondylotic myelopathy treated by anterior or posterior approach. To assess the severity of the pre- and postoperative neurological symptoms, they define an original ten-point classification scale taking into account gait and urinary disturbance, ability to manipulate objects and pain. With C2-C7 laminectomy, 60% of the patients are improved, essentially for walk. A few cases only (14%) are upgraded for upper limbs function. The authors conclude that this surgical treatment should be applied only when there is a multi-level narrowed canal and predominant lower limbs deficits. The efficacy of the anterior approach depends on complete removal of osteophytes. In cases with complete osteophytectomy, this surgical treatment can improve both the upper and lower limbs function and 77.8% good results are obtained. In a few cases it may be necessary to use both approach successively. Discriminant analysis applied to 12 factors shows that pre-operative scores of upper and lower limbs and sagittal diameter of spinal canal are the most important factors for neurological prognosis.     

Cardiocirculatory disturbances after surgery of carcinoma of the thoracic esophagus

From 1976 to 1985, 277 cases of carcinoma of the esophagus were resected in the Second Department of Surgery, Tohoku University School of Medicine. Postoperative cardiocirculatory disturbances occurred in 114 cases (41.2%), arrhythmia being the disturbance most frequently observed (86.8%). Low cardiac output syndrome occurred in 8 cases and myocardial infarction occurred in 3 cases. The majority of the cases were treated successfully, but 5 patients died within one month after operation. Causes of death were as follows: myocardial infarction, constrictive pericarditis, cardiac tamponade, non-occlusive mesenteric ischemia and acute cardiac failure. Postoperative arrhythmia occurred mainly up to the third postoperative day. Low cardiac output syndrome occurred just after operation or on the first postoperative day. All cases of myocardial infarction occurred on the first postoperative day. The rate of occurrence of cardiocirculatory disturbances in aged patients (greater than or equal to 70) was significantly higher than other group (less than or equal to 69), (56.7%:38.1%, p less than 0.05). The rate of occurrence of cardiocirculatory disturbances in patients who had a history of hypertension or in patients with abnormal preoperative electrocardiographic findings were relatively higher than those in patients who had no history of hypertension or in patients with no abnormal preoperative electrocardiographic findings. The rate of occurrence of cardiocirculatory disturbances in patients who had undergone total resection of the thoracic esophagus was significantly higher than that in patients who had undergone partial resection of the thoracic esophagus (42.8%:23.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous positive airway pressure in the treatment of postoperative hypoxia

The physiopathology of postoperative hypoxia has been analysed, the cause being identified in the worsening of the V/Q ratio consequent on the reduction in CFR. By increasing CFR, CPAP reduces the superimposition of Tidal Volume and Closing Volume, thus reducing dysventilated zones and thereby improving the V/Q ratio and oxyaemia. With these premises, 18 patients undergoing cholecystectomy were examined; 8 of them were treated in the postoperative period with CPAP at pre-established intervals. The results confirm its effectiveness in terms of PaO2 improvement and the need for constant administration, considering that the benefits are lost when the patient is disconnected from the mask.     

Quantitative immunocytology as a marker for indications and follow-up of recurrence prevention of superficial urinary bladder cancers

In 1985, we initiated a prospective clinical trial to evaluate the risk of recurrence for superficial bladder cancer. Up to now, 41 patients subjected to TUR have subsequently been monitored by immunocytology with a monoclonal antibody (mab 486 p) recently developed in our laboratory. Of these patients, 15 (36.6%) remained marker-negative and received no prophylactic therapy. There was only one recurrence (6.7%) in this subset of patients, whereas 10 out of 26 (38.5%) marker-positive patients have so far developed recurrent malignancies. In all cases, the conversion of immunocytological characteristics preceded visible recurrence by 2-5 months. These preliminary results indicate that immunocytology might make it possible to identify patients at low risk of recurrence more accurately than has so far been feasible with standard cytology or flow-cytometry.     

The hepatotropic properties of nonsteroidal anti-inflammatory agents

The hepatotropic effect of nonsteroidal anti-inflammatory drugs (NSAID) such as indomethacin, voltaren, piroxicam, phenylbutazon, mefenamic acid was studied. It was found that according to their level of the pharmacological protection of the liver against tetrachlormethan these agents may be arranged in the following sequence: mefenamic acid, phenylbutazon, voltaren, piroxicam. The hepatoprotective effect of NSAID correlates with the antioxidant properties and fails to correlate with the antioxidant ones. The hepatotoxic effect of NSAID was determined by their ability to suppress synthesis of prostaglandins.