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At least 19 recordsLinked to original sources

Longterm effects of cryosurgery in the sheep heart.

This study concerns the longterm effects of both epicardial and endocardial cryosurgery with particular reference to the coronary arteries. Sheep were subjected to epicardial cryosurgery without cardiopulmonary bypass, and to endocardial application with bypass. In both groups the heart was kept beating throughout the operation. Neither cardioplegia nor aortic cross-clamping was used. In the first group applications were made for 5 min directly over or adjacent to a major branch of the left coronary artery. In the second, the cryoprobe was applied for 5 min or until atrioventricular dissociation occurred. No sheep developed late arrhythmias or evidence of myocardial ischaemia. Only minimal arterial changes were observed and all the major coronary arteries remained widely patent. Cryothermia to the heart produced a small discrete lesion without complication. Bright fluorescence of necrotic myocytes was observed in all the immature lesions when sections stained with haematoxylin and eosin were examined under ultraviolet light. This vivid fluorescence clearly delineated the extent of the lesions and persisted while cytoplasmic elements remained. Our results indicate that cryosurgery provides a safe and permanent technique for the surgical treatment of arrhythmias in man, and may safely be used even in proximity to the coronary arteries. Cardioplegia is contraindicated.

Animals

Longterm effects of cyclophosphamide on granulocyte colony formation in patients with rheumatoid arthritis.

Longterm cytotoxic therapy, particularly with alkylating agents, is frequently associated with the development of second neoplasms, particularly acute myeloid leukemia. Twelve patients with classic, progressive rheumatoid arthritis (RA), treated with a cytotoxic agent, cyclophosphamide, from 1969 to 1974 at the University of Colorado Health Sciences Center were reassessed for current status of the granulocytic system. Bone marrow biopsies were investigated histologically and the number of granulocyte precursor cells judged using colony forming cells in culture (CFU-C). Control bone marrow biopsies were done on 8 patients with classic, progressive RA who had not taken cyclophosphamide as well as 16 healthy controls. Colony forming cell numbers in patients with RA who had been treated with cyclophosphamide were significantly lower compared to patients with RA who had not received cyclophosphamide and normal controls. These data suggest that cyclophosphamide may cause suppression of the hematopoietic system that does not totally recover even after long periods of time.

Aged

[Longterm effect and maintenance therapy with cutaneous isosorbide dinitrate in patients with coronary heart disease (author's transl)].

The aim of this study was to examine the duration of action of a single cutaneous application of a 10% isosorbide dinitrate ointment (ISDN-S) and also to ascertain the possible appearance of nitrate tolerance after 6--8 months' maintenance therapy with ISDN-S. After a single application of the ointment an effect lasting more than 7 hours was confirmed by bicycle ergometry. After longterm therapy an acute test with rapidly acting sublingual ISDN produced an undiminished response thus showing lack of nitrate tolerance.

Coronary Disease

Nifedipine in Raynaud's phenomenon: relationship between immediate, short term and longterm effects.

Sixteen patients with Raynaud's phenomenon (8 with primary Raynaud's, 8 with systemic sclerosis including 3 patients with CREST) were treated for 4 weeks in a double blind crossover study with nifedipine, 20 mg twice daily. Treatment resulted in improvement of symptoms (p less than 0.05), a lower frequency of attacks (p less than 0.05) and a tendency to a shorter duration of the attacks. Photoelectric plethysmography during nifedipine treatment showed greater amplitudes on cooling (p less than 0.05) and a better and faster recovery on rewarming (p less than 0.05) than during placebo. The immediate effect of nifedipine, 10 mg sublingually, on the amplitude of the plethysmogram, finger temperature, heart rate and blood pressure did not correlate with the effect of maintenance treatment. Dose titration based on therapeutic effect and side effects resulted in a dose of 20 mg daily for 5 patients, 40 mg for 7, and 80 mg daily for 3 patients. Longterm treatment (16-20 weeks) resulted in sustained efficacy, both by subjective and objective standards (plethysmography).

Adult

Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG.

In order to further improve the cure rate in AML we investigated the effect of more chemotherapy--in terms of its intensity and its duration--in 2 studies. In our 1981 study patients received TAD 1-2 courses for induction, 1 course for consolidation and randomly no further treatment or monthly myelosuppressive maintenance for 3 years. Evaluating 213 responders remission duration was clearly longer in the maintenance group with 24% CCR after 5 and 10 years. In our 1985 study the same successful strategy was further intensified by a second induction course given regardless of response to the first course to all patients up to 60 years of age while older patients received standard induction as before. This age-adapted concept resulted in a further increase of 5 years CCR in the 461 responders to as much as 34% not achieved for unselected patients in other multicenter trials. 20 patients receiving auto-BMT in first CR show the same relapse free survival as their counterparts receiving chemotherapy according to the 1985 protocol in a matched-pair analysis. We conclude that both very early intensification and prolonged maintenance contribute to a higher cure rate that is not further improved even by a maximum intensity short-term treatment. The limits of chemotherapy in AML may be overcome by modulating its myelotoxicity and antileukemic potency using GM-CSF as shown in 2 studies of our group.

Acute Disease

International symposium on levamisole in rheumatoid arthritis. A review of short and longterm effects on articular manifestations.

Reports of 28 authors with a total of nearly 1,000 enrolled patients have been reviewed regarding changes in clinical manifestations of disease in rheumatoid arthritis during short term and long term administration of levamisole. Global clinical improvement was observed in 60% of patients after three months and in 75% of patients after six months of drug treatment. There was no significant difference in response whether the drug was given in a continuous daily or intermittent weekly fashion. The longest observation times extend to 3 1/2 years. An optimal effect is usually reached between six and 12 months of treatment, after which time no further improvement is observed. After cessation of drug administration, the rate of deterioration varies with the length of previous exposure.

Arthritis, Rheumatoid

Longterm effect of neonatal whole-body X-ray exposure on ploidy development in mouse liver cells.

Mice of the strains C3H, DBA, NZB, and NMRI were X-irradiated with 0.475 Gy and 2.85 Gy (or 3.80 Gy) at newborn stage or at the age of six months. Their livers were prepared at the age of one to maximum 18 months and the hepatocytes isolated. The DNA content of both whole cells and separated nuclei was measured by flow cytometry and the liver ploidy pattern was determined applying a correcting calculation. Irradiation with 0.475 Gy of newborns of strain C3H results in a relative decrease of octoploid cells and an increase of tetraploid nuclei during lifetime (significance level of 0.001). After irradiation with 3.80 Gy a reversed reaction was observed. However, if the animals were irradiated as adults with a dose of 3.80 Gy the 8c cells decreased significantly three months later. Similarly, newborns of the outbred strain NMRI irradiated with 2.85 Gy, showed an increase of octoploid cells from the third month on, but an oscillating pattern of the 4c nuclear DNA content. In strains DBA and NZB, significantly altered ploidy values could not be found, perhaps due to a too great variance of experimental values.

Age Factors

Longterm effects of early cadmium exposure on locomotor activity in the rat.

The present study investigated the hypothesis that changes in the frequency of specific behaviors, not assessed by the traditionally employed global measures of locomotor activity, may occur following exposure to cadmium. Two groups of newborn male rat pups were treated orally with either 1.0 mg/kg CdCl2 for 14 days or 10.0 mg/kg CdCl2 for one day followed by 13 days of the treatment vehicle only. A control group received only the vehicle. At 50 days of age, animals were observed in their home cage for 12 hours and the amount of time spent engaged in each of eight separate categories of behavior was recorded. Subsequently, exploratory behavior in an open field was assessed. The single large dose of cadmium resulted in weight loss and a significantly slower growth rate significantly increased rearing in the home cage and significantly decreased inner square exploratory behavior in the open field. Implications of emotional hyporeactivity and physiological explanations which may account for the differences observed between the two treatment regimens are discussed.

Animals