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Biomedical subjects

A Senning

Publications and source records attributed to A Senning.

At least 19 recordsLinked to original sources
PubMed1991

Enzymatic and nonenzymatic in vitro hydrolysis of 2-methyl-2-[2-(methoxy)phenoxy]-4H-1,3-benzodioxin-4-one and 2-methoxyphenyl O-acetylsalicylate.

This paper is concerned with the synthesis and physical properties as well as the enzymatic and nonenzymatic in vitro hydrolysis of the potential aspirin prodrug MR 693 (5) and the salicylic acid prodrug guacetisalum (6). The half-lives of both prodrugs and the amount of aspirin regenerated in each hydrolytic run for 5 have been estimated over a wide range of pH values.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Atrial repair for transposition of the great arteries: current approach in Zürich based on 24 years of follow-up.

Long-term survival after atrial repair of a transposition of the great arteries between 1964 and 1988 is analyzed in 254 thirty-day survivors. For the complete series, overall survival is 99.6% after one year, 94.9% after 6 years, 89.6% after 12 years, 84.9% after 18 years, and 64.0% after 24 years. Broken down for simple (154/254) versus complex (95/254) transposition survival, it is 99.4% versus 100.0% for one year, 94.7% versus 99.5% for 6 years, 90.8% versus 88.3% for 12 years, 85.1% versus 85.8% for 18 years and 77.7% versus 46.8% at 24 years. Survival for patients without or with VSD is 95.3% versus 96.2% after 6 years, 91.2% versus 87.9% after 12 years, 87.5% versus 84.0% after 18 years, and 83.7% versus 52.5% after 24 years. Cumulative survival as a function of the surgical approach for VSD closure is 94.3% for transatrial versus 92.3% for transventricular at 6 years, 82.2% versus 92.3% after 12 years, 82.2% versus 83.0% after 18 years and 82.2% versus 41.5% after 24 years. Survival for patients operated upon before 1978 is 94.3% versus 96.0% thereafter at 6 years, and 90.7% versus 89.2% at 12 years (NS). Linearized mortality rates are 1.49% per patient year for the complete series, 0.93 for simple transpositions, 2.21% for complex transpositions (including VSD, obstruction of the left ventricular outflow tract, or both), 0.68% for transpositions without VSD, 1.98% for transpositions with VSD, 2.43% for transposition with transventricular repair of a VSD, 1.74% for transposition with transatrial closure of a VSD, and 0.90% for all cases operated upon after 1978.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1990

Aspirin prodrugs: synthesis of 2-substituted 2-methyl-4H-1,3-benzodioxin-4-ones and their screening for prodrug potential.

A series of new 2-substituted 2-methyl-4H-1,3-benzodioxin-4-ones 1 have been synthesized and fully characterized. This study involves fifteen compounds of which fourteen are orthoesters, containing tertiary aliphatic alkoxy groups. One compound contains a tert-butylperoxy group and one a 3 beta-cholesteryloxy group in the 2-position. The hydrolysis of these compounds 1 was followed in enzymatic and non-enzymatic media to clarify whether they are true prodrugs of aspirin. Two compounds 1 were additionally tested in vivo as potential topical keratolytics.

Animals↗
PubMed1989

[Long-term course of hypertrophic cardiomyopathy: drug versus surgical therapy].

139 patients with hypertrophic cardiomyopathy (HCM) have been followed up for 1-28 years (mean 8.9 years). Group 1 consisted of 60 patients (mean age 38 years) without indication for septal myectomy (SM) (no pressure gradient at rest in 8, pressure gradient less than 50 mm Hg in 52 cases); group 2 consisted of 79 patients (mean age 36 years) who had SM (pressure gradient at rest 70 mm Hg). Management in group 1 was the following: (1a) propranolol (n = 20) (160 mg/d), (1b) verapamil (n = 18) (360 mg/d) and (1c) no therapy (n = 22). 19 patients died in group 1 (mortality 3.6% year); 17 died in group 2 (mortality 2.4%/year). 10 year survival in group 1b was 80% and in groups 1a und 1c 67% and 65% respectively. Patients of group 1b had a higher survival rate (p less than 0.05) than the other subgroups. Surgery patients treated with verapamil (120-360 mg/d) (n = 17) had a 10-year survival rate of 100% compared to 78% for surgery patients (n = 34) without such treatment (p less than 0.05). In summary, it can be said that the overall survival rate after SM is better than that with medical treatment. Under verapamil, however, survival is not different from that after surgery. The most favorable outcome was observed in surgery patients under long-term therapy with verapamil, probably due to the reduction of systolic pressure overload (SM) and improvement in diastolic function (verapamil).

Adult↗
PubMed1989

Late failure of systemic ventricle after atrial correction for transposition of great arteries.

The incidence of late systemic ventricular failure (SVF) was determined in 220 early survivors of atrial correction for transposition of great arteries (TGA), operated upon between 1964 and 1985. SVF was defined as either severe heart failure (NYHA class III or IV) or death due to the same cause, in the absence of other haemodynamic disturbances. The actuarial survival rate was 96% after 1, 94% after 5 and 87% after 10 years. SVF occurred in 16/220 patients (7.2%). SVF was more common in complex TGA (TGA + VSD or PS or both) with 11/99 patients (11%) than in simple TGA with 5/121 patients (4.1%), P less than 0.01. Actuarial freedom from SVF was 97% at 5, and 92.5% at 10 years. SVF caused 10/25 (40%) late deaths. SVF occurred from the 1st postoperative year up to 20 years after correction (average interval 6.3 years). In 1 of 2 patients a systemic atrioventricular (AV) valve annuloplasty did not improve SVF. Heart transplantation was performed in 2 patients and 1 is on the waiting list. SVF is a rare late complication of atrial correction for TGA with a constant incidence in the late course. SVF is more common in complex TGA.

Actuarial Analysis↗
PubMed1989

Aspirin prodrugs: synthesis and hydrolysis of 2-benzyloxy-2-methyl-4H-1,3-benzodioxin-4-ones.

Aspirin is widely used for its analgesic, antiinflammatory and antipyretic properties. Among its disadvantages are the relatively narrow therapeutic margin, its irritancy towards the gastric mucosa, and occasionally patient hypersensitivity towards aspirin. As part of our effort to develop prodrugs without these liabilities eleven new title compounds have been isolated and characterized. These 'superaspirin' candidates were subjected to non-enzymatic hydrolysis for a first rapid screening in vitro. Only 2-(2,6-dimethoxybenzyloxy)-2-methyl-4H-1,3-benzodioxin-4-one (4c) was observed to act as an exclusive aspirin prodrug, while 2-(2-methoxybenzyloxy)-2-methyl-4H-1,3-benzodioxin-4-one (4b) and 2-(2-ethoxybenzyloxy)-2-methyl-4H-1,3- benzodioxin-4-one (4d) were shown to release both aspirin 6 and salicylic acid 7. Subsequently, these three candidates were further characterized by investigation of the pH profile of their hydrolysis rates.

Aspirin↗
PubMed1989

Developments in cardiac surgery in Stockholm during the mid and late 1950s.

In 1951 in our laboratory in Stockholm, we successfully used our experimental pump oxygenator: the first dogs survived 40 minutes of total cardiopulmonary bypass with right ventricular cardiotomy. In the same year extracorporeal circulation was combined with hypothermia (26 degrees to 28 degrees C) to allow lower perfusion flows, thus diminishing blood trauma and the risk of perfusion complications. To avoid air emboli during cardiotomies, the heart was "arrested" with electrically induced ventricular fibrillation (1952). Our standard perfusion technique used cooling and rewarming with left ventricular bypass, the oxygenator was used only during intracardiac manipulations and when the right ventricle was unable to maintain a sufficient pulmonary circulation. Left ventricular bypass was continued until normal body temperature was reached and the heart could be weaned off the pump. In July 1954 we successfully extirpated a left atrial myxoma in our first patient undergoing open heart surgery, a 40-year-old woman, who is still alive today. Other successful applications of open heart surgery involved resection of a huge left ventricular aneurysm after infarction in 1955, correction of supracardiac total anomalous venous return in 1956, and the first hemodynamic correction of transposition of the great arteries by atrial switch method in 1958. Also in 1958, the first totally implantable pacemaker was inserted in a patient with total atrioventricular block to eliminate the infections that occurred along the percutaneous pacemaker leads. In October 1958, we also operated on a patient with severe angina pectoris with stenosis of the left anterior descending and circumflexed arteries and occluded right coronary artery. Endarterectomy of the left coronary arteries was performed, and the arteriotomies were repaired with saphenous vein patches.

Animals↗
PubMed1989

Late functional deterioration after atrial correction for transposition of the great arteries.

Late anatomic and functional results were evaluated in 220 consecutive survivors who underwent surgery in 1964-1984 for atrial correction of transposition of the great arteries (TGA). Actuarial survival was 87% at 10 years and 83% at 20 years and was higher in patients with simple than in those with complex TGA (92% vs. 84% at 10 years). Although 83% of simple TGA and 78% of complex TGA survivors belong to the oligosymptomatic or asymptomatic group, failure of the systemic ventricle occurred in 17 (7.7%) patients. This failure was more common in patients with complex than in those with simple TGA (12.1% vs. 4.1%, p less than 0.05); actuarial incidence of such failure was 3% at 5 years and 11% at 15 years, and it caused 10 of 25 (40%) of late deaths. Late dysrhythmias necessitating pacemaker implantation had an incidence of 9.8% at 10 years. Reoperations were performed in 20 (9.1%) patients, with 12 of 23 (52%) reoperations occurring in the first 2 years after correction. Stenosis of caval inflow (eight patients), or residual atrial or ventricular septal defects (eight patients) were the most common causes of reoperation. Systemic atrioventricular valve incompetence necessitating surgery occurred in only three patients. Atrial correction gives good late results, but late functional deterioration occurs in some patients.

Child↗
PubMed1988

Long-term outlook after atrial correction of transposition of great arteries.

Late results were reviewed in 220 survivors after atrial correction of transposition of the great arteries who were operated between 1964 and 1985. Senning's procedure and its various modifications have been used; all patients who survived 30 days after correction were included in this analysis. Average follow-up for the whole group was 10.3 years; 113 patients were observed for 10 years, 26 patients for 15 years, and 8 patients for 20 years. The actuarial survival rate for the whole group was 89% at 10 years, 87% at 15 years, 82% at 20 years. It was higher in simple than in complex transposition (92% versus 84% at 10 years). Sudden deaths (8 patients) and late heart failure (6 patients) were the principal causes of death, predominantly in the complex transposition group (10/13 deaths). Late survival was more common in the latter part of the study, with 95% of patients operated on after 1978 surviving 9 years as opposed to 84% of patients operated on earlier. Late reoperation was necessary in 18 patients (8%), with 12 reoperations occurring within 2 years after correction. Cumulative reoperation rate reached 11.7% after 10 years. Reoperations were more common in complex than in simple transposition (14% versus 6%, p less than 0.05). Late arrhythmias can occur after atrial correction, and the cumulative incidence of pacemaker implantations was 8% at 10 years. Most of the survivors are functionally free of symptoms (83% of the simple and 75% of the complex transposition group). Significant tricuspid valve incompetence was encountered in only three patients, with two valve reconstructions being possible. In summary, long-term outlook for survivors of atrial correction for transposition of the great arteries remains encouraging, although complex transposition does seem to engender more late problems. Atrial correction is still warranted in simple transposition, but close cardiological surveillance is necessary.

Actuarial Analysis↗
PubMed1987

Coarctation of the aorta: review of 362 operated patients. Long-term follow-up and assessment of prognostic variables.

362 patients operated upon for coarctation of the aorta from 1961-1980 were analyzed retrospectively. Age at operation was less than 2 years in 74 (group A) and greater than or equal to 2 years in 288 patients (group B). Associated cardiovascular malformations were common, especially in group A patients. Early mortality was 12.2% for group A and 1.4% for group B patients. 336 patients were followed for 6 months to 21 years (mean 8.9 years). Late mortality was 0.8% per patient year. Associated cardiac defects and postoperative hypertension were responsible for most of the late deaths. Late reoperations were performed because of aortic valve disease, residual coarctation (with persistent hypertension) and aortic aneurysms at the site of anastomosis. The incidence of hypertension decreased from 82.5% preoperatively to 33.5% at discharge from the hospital. It decreased further during follow-up in patients operated less than 10 years of age, but remained constant in the older patients. In conclusion, morbidity and mortality after operative repair of coarctation are determined mainly by (1) associated cardiac malformations, and (2) postoperative hypertension. Patients with isolated coarctation and postoperative normal blood pressure have an excellent prognosis. Patients operated upon from between 2-9 years of age carry the lowest risk for residual coarctation and late postoperative hypertension.

Aortic Aneurysm↗
PubMed1986

[Vocational rehabilitation after an aortocornary bypass operation].

To elucidate the influence of coronary bypass surgery on vocational status we studied 238 male patients operated upon for stable angina (mean age 53.3 +/- 7.4 years). The postoperative follow-up was 3.7 +/- 0.7 years. 33 patients died or had to be excluded because they had retired. 113 (55%) of the remaining 205 patients participated in a formal rehabilitation program (group A), whereas 92 (45%) patients did not (group B). There was no significant difference between the two groups with regard to pre- or postoperative clinical and angiographic data, except a higher rate of preoperative unemployment and of patients unfit to work for more than 6 months before operation in group B. The overall preoperative employment rate was 48%, whereas 3.7 years after operation 62% of all the patients were working (p less than 0.005), a net gain of about 30%. Return to work was significantly influenced by the NYHA classification after operation, exercise capacity in the bicycle stress test, duration of preoperative unemployment, type of work and age at operation. In group A the postoperative employment rate was higher than in group B (72% vs. 51%), especially in patients who had not worked before operation (62% vs. 32%). It is concluded that after coronary artery bypass surgery a net gain in employment rate can be expected and a formal rehabilitation program may help the patients to resume work postoperatively. However, definite conclusions cannot be drawn because of the retrospective, nonrandomized design of the study.

Adult↗
PubMed1986

Treatment of Budd-Chiari syndrome by dorsocranial liver resection and direct hepatoatrial anastomosis.

Since 1980 an operation which reestablishes the blood outflow from occluded hepatic veins was performed in 7 patients with Budd-Chiari syndrome by one of us (A. Senning). Using extracorporeal circulation a dorsocranial cylindrical resection of the liver including the confluence of the occluded hepatic veins was performed by transcaval approach. The incised right atrium was sutured around the resected liver area. There was one intraoperative death. In 6 patients with a mean postoperative follow-up of 19.2 months (4-42 months), the patency of hepatoatrial anastomosis was documented by angiography or Doppler-2d-echocardiography. Four patients are free of symptoms and signs of Budd-Chiari syndrome. In one of two patients with associated cirrhosis compression of inferior vena cava reoccurred and in another patient esophageal varices persist. We conclude, that the hepatoatrial anastomosis is an effective treatment of Budd-Chiari syndrome.

Adult↗
PubMed1986

Experience with the helix cava filter.

A new caval filter of helico-spiral geometry (Helix-Filter) was implanted in 13 patients for the prevention of pulmonary embolism (PE). The indications for implantation were: recurrent PE despite adequate anticoagulation (5 cases) or contraindication to anticoagulation (3 cases), incomplete local therapeutic fibrinolysis after severe paracentral PE (2 cases), and prophylaxis in high risk patients (3 cases). Implantation was effected by the saphenous/femoral vein approach in 12 patients, and via the right atrial appendage during open heart surgery in one instance. There were no intraoperative technical problems and in no case was the filter misplaced. During the follow-up period (mean 14.8 months, maximum 28 months) no filter-related complications were encountered. One patient with an exceptionally enlarged vena cava, due to abnormal renal vein inflow, had a fatal recurrent PE despite high dosage heparinization. One patient with an event-free follow-up died 12 months after filter placement from unrelated diseases. The remaining 11 patients are free of symptoms with no recurrent PE, no deterioration of venous circulation or presence of caval thrombosis. Emboli trapped at the filter were documented in 2 patients; spontaneous resolution occurred in one case. Experimental and early clinical results indicate that the hemodynamically optimal design of the Helix-Filter permits controlled and uniform luminal filtering with high patency. As such, it represents an alternative and highly promising solution to the problem of "mechanical" prevention of pulmonary embolism in selected patients.

Adult↗