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At least 19 recordsLinked to original sources

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

[The effects of longterm selection on the genetic structure of populations--a simulation study. II. The effects of selection on genetic variances].

Monte Carlo simulation has been done to study the effects of longterm artificial selection on genetic variances under additive, dominant, and over-dominant models. The effects of population size, linkage, and heritability have been considered. Just as under the additive model, the additive variance under the dominant and over-dominant models has also been decomposed into three components which represent changes in gene frequencies (VT), departure from Hardy-Weinberg equilibrium (VHW) and from linkage equilibrium (VLD) respectively. These present a resonable approach to study the association among multiple genes. In small populations, genetic variance fluctuates wildly over generations and replicates due to the establishment of linkage disequilibrium. Rapid decrease of VT observed. Intense linkage retained a greater additive variance in the small populations while slowing down responses, which makes it difficult to predict responses during longterm selection.

Animals

The effect of longterm treatment with auranofin and gold sodium thiomalate on immune function in the dog.

Although gold compounds are recognized as effective immunomodulatory agents in the treatment of rheumatoid arthritis (RA), their mechanism of action is controversial. We examined the effect of longterm treatment with 0.6-3.6 mg/kg auranofin (AF) per os q24h, or intramuscular injections of 0.5-2.0 mg/kg gold sodium thiomalate (GSTM) q3d, on 13 variables of immune function in normal dogs. None of the changes in these variables previously attributed to treatment with AF or GSTM could be demonstrated after 6-7 years' dosing. As gold compounds are effective in treating spontaneous RA in dogs, these proposed actions may not be responsible for the remittive effects of chrysotherapy in this disease.

Animals

[Effects of longterm selection on the genetic structure of populations--a simulation study. I. Simulation models and selection responses].

Monte Carlo method has been utilized to investigate responses to longterm selection. The simulation involves 3 gene effect models (additive, dominant, and over-dominant), two population sizes, three linkage intensities, and three heritability levels, thus making 54 combinations. For each combination, 5 replicate populations are selected over 49 consecutive non-overlapping generations. The results demonstrate that under all the gene effect models, linkage is important only in the case of small populations and intense linkage, when it reduces responses significantly due to hampering the fixation of favourable alleles and accelerating their loss. Linkage has no apparent effect if it is not very tight or if the population is large. Much greater responses are achieved in the large populations than in the small ones, especially for traits with low heritability. Among those discussed are problems of crossing selected lines to obtain extra responses, and discrepancy of some theoretic results on selection limits.

Computer Simulation

[Side-effects on longterm treatment with antihypertensives (author's transl)].

Unspecific complaints as a result of lowering the blood pressure and substance-specific side-effects may occur during antihypertensive therapy. The frequency of the side-effects depends on the substance used (10 to 50%) and on the dose. An individual therapy, which in most cases involves the use of several substances, can reduce the frequency of side-effects decisively. With optimal therapy the ratio of benefits (= prevention of cardiovascular diseases) to side-effects (= sum of undesirable reactions) is completely acceptable in the treatment of high blood pressure.

Age Factors

Longterm favorable effect of oxygen administration on a patient with primary pulmonary hypertension.

A 17-year-old girl with primary pulmonary hypertension was treated with longterm administration of oxygen. Oxygen was delivered only at night for eight hours daily. Her clinical status has been improved for more than 17 months. Cardiac catheterization revealed almost 50 percent reduction of pulmonary vascular resistance. This is the first known report of successful treatment of primary pulmonary hypertension with oxygen administration.

Adolescent