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PubMed1976

[A comparison of the tranquilizing effect of fluspirilene and diazepam (author's transl)].

Over a period of 8 weeks we compared the tranquilizing effects of the longterm neuroleptic Fluspirilene to those of Diazepam in a series of 28 patients. Both drugs showed good effects on somatization, anxiety and depressive mood. Fluspirilene, however, proved to be the more mood elevating and more activating agent without being hypnotic. The indications for both drugs are being discussed emphazising the new therapeutic perspectives of a long acting tranquilizer.

Anxiety↗
PubMed1984

Effect of angiotensin II on RNA synthesis by isolated nuclei.

Peptide hormones are known to bind to cell surface receptors as the first step in the generation of their effects on target tissues. However, it remains uncertain whether internalized hormone might also play a role in the production of longterm or trophic effects of peptide hormones. Because the peptide hormone angiotensin II appears to be internalized by target cells, we studied the effect of this peptide on isolated hepatic nuclei. At both 5 X 10(-7)M and 5 X 10(-9)M, angiotensin II significantly increased RNA synthesis. This effect was not mimicked by Sar1-Ala8-angiotensin II (saralasin) or the unrelated nonapeptide teprotide.

Angiotensin II↗
PubMed2003

Comparison of antiproteinuric effects of two different combination therapies in children with IgA nephropathy.

BACKGROUND: Because moderate or severe proteinuria is a representative factor indicative of longterm poor prognosis in IgA nephrology, an anti-proteinuric treatment which can be administered longterm with few side effects is necessary. We report here a comparison of antiproteinuric effects in two patient groups treated with different combination therapies. METHODS: Group A comprised 12 patients with IgA nephropathy, who had 24-h proteinuria of 0.5 gm(2) or more, moderately severe renal histology, and normal renal function, and were treated with a combination of drugs, i.e., prednisolone, an immunosuppressant (mizoribine), an anti-platelet drug (dipyridamole), and an angiotensin-converting enzyme inhibitor. Group B consisted of 18 patients who had baseline characteristics similar to those of the patients in group A and were treated with our previous protocol (a combination of prednisolone, cyclophosphamide, and dipyridamole). Twenty-four-hour proteinuria and creatinine clearance were measured every 6 months. The primary endpoint was reduction of 24-h proteinuria by less than 25% compared with the baseline value. RESULTS: The proportion of patients that exhibited the primary endpoint, as assessed by the Kaplan-Meier method, was found to be significantly higher in group A than in group B (logrank test; P = 0.024). None of the patients in the two groups experienced serious adverse effects. CONCLUSIONS: The results suggested that the use of drugs in combination with cyclophosphamide was beneficial for patients with moderately severe IgA nephropathy. Because moderate or severe proteinuria is a representative factor indicative of longterm poor prognosis in IgA nephropathy, an anti-proteinuric treatment which can be administered longterm with few side effects is necessary. We report here a comparison of antiproteinuric effects in two patient groups treated with different combination therapies.

Adolescent↗
PubMed1997

Longterm ultraviolet-A1 irradiation therapy in systemic lupus erythematosus.

OBJECTIVE: In a recent series of short term studies ultraviolet-A1 (UV-A1; 340-400 nm) dermal irradiation proved effective in reducing signs and symptoms of disease activity in patients with systemic lupus erythematosus (SLE). To determine if the effectiveness persisted with longterm therapy, we followed the progress of 6 of these patients for an average of 3.4 (range 2.4-4.5) yrs. The 6 had had significant decreases in signs and symptoms of disease activity during the first 12 weeks of the earlier studies while receiving 3 to 5 low dose UV-A1 irradiations weekly and were asked to continue into longterm therapy. METHODS: Longterm therapy consisted of 1 or 2 irradiations of 6-15 J/m2 (15-30 min, or about 1/8-1/4 minimal erythema dose) per week. We assessed their progress every 3 mo with the systemic lupus activity measures. RESULTS: Despite the smaller number of weekly treatments, the gains achieved during the initial 12 weeks of the early studies not only persisted but increased slightly. Tanning was moderate to absent, the therapy was well tolerated, and there was no apparent toxicity. CONCLUSION: UV-A1 radiation induced remissions in SLE persist with longterm therapy; 1 or 2 weekly exposures suffice; there appears to be no significant toxicity.

Follow-Up Studies↗
PubMed2004

The influence of statin characteristics on their safety and tolerability.

The efficacy of the statins for both primary and secondary prevention has now been clearly established in patients across the spectrum of cardiovascular risk. In addition to their primary effect in reducing plasma cholesterol, the statins possess various 'pleiotropic' effects that may contribute to their clinical effectiveness in reducing cardiovascular events, e.g. improvement of endothelial function, reduction of low-density lipoprotein-cholesterol oxidation and stabilisation of atheromatous plaques. Although statins share similar chemical characteristics, they differ significantly in terms of their molecular synthesis, solubility and pharmacokinetic behaviour and metabolism. Side-effects secondary to longterm statin therapy are rare, but rhabdomyolysis may occur when statins are administered together with other drugs that have a direct toxic effect on muscle or which inhibit statin metabolism. Among the various statins, it would appear that fluvastatin has the lowest propensity to interact with other drugs and the least potential to induce myotoxicity.

Cardiovascular Diseases↗
PubMed2005

Laparoscopic adjustable gastric band.

Only a fraction of morbidly obese patients have come forward for bariatric surgery. This article confirms that the laparoscopic adjustable gastric band (LAGB) is a safe, effective, primary weight-loss operation for morbidly obese patients. The LAGB offers a simple, genuinely minimally invasive approach, with the potential to be attractive to many more patients. The key questions are whether it is effective in the longterm and whether it is safe. The midterm data confirm that, so far, LAGB is living up to its early promise as an effective tool. LAGB surgery is safe, and the change to the pars-flaccida approach will lead to even higher patient satisfaction and lower incidence of band removal.

Gastroplasty↗
PubMed2000

A randomized, multicenter, controlled trial using intravenous pulses of methylprednisolone in the initial treatment of simple forms of giant cell arteritis: a one year followup study of 164 patients.

OBJECTIVE: (1) To evaluate the corticosteroid sparing effect of an initial intravenous (i.v.) pulse of methylprednisolone (MP) in the treatment of simple forms of giant cell arteritis (GCA). (2) To analyze corticosteroid response, steroid related side effects, and GCA complications. METHODS: Patients received a 240 mg i.v. pulse of MP followed by 0.7 mg/kg/day oral prednisone (Group 1) or 0.7 mg/kg/day prednisone without an i.v. pulse (Group 2, controls), or a 240 mg i.v. pulse of MP followed by 0.5 mg/kg/day prednisone (Group 3). Corticosteroid dosage was reduced after normalization of 2 biological inflammatory variables to obtain half-dosage after 4 weeks in Groups 1 and 2 and 20 mg/day after 2 weeks in Group 3. Tapering was systematically attempted from the 6th month of treatment. RESULTS: One hundred sixty-four patients were included in the trial (1992-96). Cumulative doses of corticosteroids after one year were identical for all groups (p = 0.39). No significant differences were observed in the time required for normalization of C-reactive protein, corticosteroid resistance (13.5%), and corticosteroid related side effects (39% of patients; p = 0.37). Corticosteroid resistant patients received larger doses and showed a high risk of GCA related complications (p = 0.02). CONCLUSION: MP pulses have no significant longterm, corticosteroid sparing effects in the treatment of simple forms of GCA and should be limited to complicated forms. Moreover, corticosteroid resistance is a real risk factor for GCA complications.

Adjuvants, Immunologic↗
PubMed1994

[Treatment of advanced and recurrent gynecologic cancer with chemotherapy by cannula perfusion into both internal iliac arteries].

This paper reports fourteen cases of advanced and recurrent gynecologic cancers treated with prolonged arterial perfusion chemotherapy by catheterization of both internal iliac arteries through femoral arteriopuncture under X-ray. The immediate effective rate was 78.5%, follow-up rate 100%. By this technique anticancer drugs can be selectively injected into vessels supplying the tumors. The drug is concentrated within the tumor resulting in longterm better local effects, and fewer general side reactions, and a much higher dose than that which could be given conventionally. This technique is considered as a new route of treatment in gynecologic tumors.

Adult↗
PubMed1979

[Long lasting psychotropic effects after long-term treatment with a hemoderivative].

Up to now there has been scarcely any publication of precise tests on the duration (lasting effect) of psychotropical effects which have appeared in brain activity after conclusion of a longterm therapy with vasoactive or metabolical substances. In 32 patients with symptoms of arteriosclerosis (average 72 years) a six weeks trial treatment was carried out with the haemoderivat Actihaemyl (6 weeks twice weekly 10 ml i.v.) according to the double blind method and checking the results with variance analysis. In the following mental areas positive effects have been proved: memory functions, creative behaviour, general psychophysical behaviour and in emotional, social and clinical behaviour. 12 weeks after conclusion of the therapy it was observed, that with the same test method there was a wide maintenance of the improvements in the psychical performance and this exceeded in many areas the status as observed immediately after conclusion of the therapy. The reason for this longterm effect of the haemoderivat which was under test is discussed.

Actihaemyl↗
PubMed1993

Adverse effects of low dose methotrexate therapy in rheumatoid arthritis.

OBJECTIVE: To determine (1) the risk of treatment termination for low dose, weekly methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA), and (2) the prevalence, nature and predictors of adverse effects due to longterm low dose MTX therapy. METHODS: A 13-year, retrospective survey of all patients with RA receiving low dose MTX therapy was conducted using life table, logistic regression and case control methods of analyses. Major and minor adverse effects were defined. RESULTS: Consecutive patients with RA (144) starting MTX (mean dose 8.2 mg/week) were observed to have a 75% risk of treatment termination at 60 months. Reasons for 81 patients stopping MTX were adverse effects (43), loss/lack of effect (18), other medical and nonmedical reasons (13), and lost to followup (7). Sixty-two patients experienced 83 major adverse events, including gastrointestinal symptoms (29), hepatic enzyme test abnormalities (23), pneumonitis (5) and severe leukopenia (8). Aging was the only predictor of treatment discontinuation associated with a major toxicity. Five patients developed a malignancy during the observation period. CONCLUSIONS: In our survey the risk of treatment termination was 75% in patients with RA taking MTX after 60 months. An adverse drug effect is a more common reason for treatment termination (53%), compared to loss/lack of beneficial effect (22%) or other reasons (16%) or lost to followup (9%). Increasing age is associated with an increased risk of treatment termination associated with a major toxicity.

Adult↗
PubMed1985

Repair function in organ cultured human cartilage. Replacement of enzymatically removed proteoglycans during longterm organ culture.

The effect of enzymatic removal of proteoglycans (PG) from the extracellular matrix of human articular cartilage on subsequent PG metabolism of the remaining chondrocytes was investigated for periods of up to 12 weeks. Chondrocytes resynthesized normally aggregated PG but these macromolecules failed to stabilize in the intercellular matrix of the organ cultured explants and consequently diffused into the nutrient medium. After being in culture for about 2 months the chondrocytes no longer compensated for this PG loss and ceased to synthesize these biopolymers. A shift towards hyaluronic acid synthesis--as seen in dedifferentiated chondrocyte cultures--was not observed during the culture period. In this model some attempts at repair were demonstrated.

Cartilage, Articular↗
PubMed2004

[Regenerative medicine for pancreatic beta cells].

Regenerative medicine involves varying degrees of interaction among many research domains. Regenerative medical therapies based on research into organogenesis and the regeneration of injured or dysfunctional tissue using cell therapy are being developed rapidly. For the treatment of diabetes mellitus (DM), pancreatic transplantation and islet (pancreatic endocrine) cell transplantation are considered to be one form of regenerative medicine to overcome pancreatic tissue dysfunction. Recently, the effective islet cell transplantation Edmonton protocol has been established, ushering in a new era in regenerative therapy for DM. However, unresolved problems remain, including a severe donor shortage and unexpected side effects with the longterm use of some immunosuppressive agents. With continuing advances and the clinical application of fundamental therapy for DM, a pancreatic islet cell transplantation or bioartificial pancreatic transplantation system, consisting of islet (pancreatic endocrine) cell purification, pancreatic cell proliferation techniques, immunoisolative membrane technology, and an appropriate transplantation procedure, will be effective. This paper focuses on applied research on human and/or porcine pancreatic cell purification, embryonic stem cell differentiation, and pancreatic stem cell differentiation into functional insulin-producing cells.

Animals↗
PubMed1996

[Results of tests with clomiphene and choriogonadotropin in men with oligozoospermia treated with longterm antiestrogens].

The evaluation was made of the response to testosterone and oestradiol in the test (50 mg twice daily for 10 days) and HCG test (6000 units of Biogonadyl through 2 days) performed on 21 normospermic (fertile) males and on patients with normogonadotropic, idiopathic oligozoospermia, positively (12 patients) or negatively (24 males) reacting to the longterm Clostilbegyt treatment (50 mg daily for 240 days). It was shown that patients with oligozoospermia who do not react with an increase of spermatozoa during the longterm antioestrogen treatment had higher response of oestradiol in the dynamic test (+ 118.9%) than the normospermic males (+ 60.8%) or the oligozoospermic who showed positive semenologic response to the treatment (+ 58.8%). The similar reaction of oestradiol was shown in the HCG stimulation. In the hiperoestrogenism phenomenon the authors noticed the cause of lack of positive semenologic effects of the longterm antioestrogen treatment.

Chorionic Gonadotropin↗
PubMed1985

Neuropsychological assessment of substance abusers: review and recommendations.

Neuropsychological assessment of substance abusers frequently proves useful for the evaluation of those aspects of cognitive functioning that may be relevant for optimal therapeutic management and treatment planning. Research has demonstrated the presence of neuropsychological impairment in chronic abusers of CNS depressants, including alcohol, as well as opiates and possibly cocaine, especially when such substances are combined in a polydrug pattern of abuse. Clinical neuropsychological evaluation of individual substance abusers should take into account the various personal, demographic and neuromedical background variables that can affect cognitive functioning. Efforts should be made to distinguish between acute drug effects and more longterm stable deficits that may not become apparent for some time. Neuropsychological referrals should be made, and measures selected to answer particular questions about neurocognitive functioning that are relevant to treatment and eventual overall adjustment. A neuropsychological review of systems is likely to show a pattern of impairment in substance abusers that involves the integration of different cognitive functions for effective problem solving. Strongly focal or lateralized deficit patterns are less likely to be the result of drug abuse alone, and should prompt the appropriate neuromedical follow-up.

Adolescent↗
PubMed1984

[Anti-ischemic effect of 8 mg molsidomin in retard form].

Studies of the efficacy of molsidomine, previously performed on our service, demonstrated that a clear antianginal effect in the longterm treatment of angina pectoris could only be achieved with a regimen of the standard 2 mg dose when given six times daily. Consequently, since a mode of administration with a longer duration of action was implicitly desirable, the present study, carried out in eleven patients with coronary artery disease and stable, exertional angina pectoris, was undertaken to assess the antiischemic effects of 8 mg molsidomine in sustained-release form as compared with the standard 2 mg formulation according to a double-blind, randomized, crossover, placebo-controlled protocol. Additionally, plasma concentrations of molsidomine were determined to elucidate the bioavailability as well as possible correlations between plasma concentrations and antiischemic effect. As compared with placebo, after administration of 8 mg molsidomine sustained-release there were reduction in the ST-segment depression at one, three, five and eight hours of 74% (p less than 0.001), 61% (p less than 0.001), 44% (p less than 0.025), and 31% (p less than 0.01), respectively; after 2 mg molsidomine, 74% (p less than 0.001), 37% (p less than 0.025), 7% (ns) and 6% (ns), respectively. Analysis of the response of the ST-segment in the individual patients showed an unequivocal antiischemic effect with a reduction in ST-segment depression of at least 1 mm after 8 mg molsidomine sustained-release at the specified points in time in ten, five, six and four patients, respectively, and after 2 mg molsidomine in nine, five, one and no patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed2005

Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis.

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and statins (hydroxy-methyl-glutaryl-CoA reductase inhibitors) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis (RA). METHODS: A total of 45 patients with longterm RA were randomized into 3 groups to receive 8 weeks of treatment with placebo (n = 15), simvastatin (20 mg/day, n = 15), or quinapril (10 mg/day, n = 15) as an adjunct to existing antirheumatic drug treatment. Factors with a role in the development of endothelial dysfunction, such as C-reactive protein (CRP), fibrinogen, nitric oxide (NO), and serum cytokine concentrations including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and in the posttreatment period. Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions. RESULTS: Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups. Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [from 5.3 +/- 1.1% to 8.9 +/- 1.4% (p = 0.025)], while there was no difference in endothelium-independent vasodilatation [9.0 +/- 1.8% to 11.2 +/- 2.5% (p = 0.17)]. The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [from 6.1 +/- 0.8% to 7.8 +/- 0.7% (p = 0.06)]. Treatment with the 2 drugs had no significant effects on resting arterial diameter. CONCLUSION: We show that simvastatin 20 mg daily improves endothelial function in patients with RA. Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response.

Adult↗
PubMed2003

Endoscopic injection sclerotherapy for esophageal varices in cirrhotic patients without hepatocellular carcinoma: a comparison of longterm survival between prophylactic therapy and emergency therapy.

BACKGROUND: This study aimed to determine whether prophylactic endoscopic injection sclerotherapy prolonged survival in patients with esophageal varices complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy. METHODS: The subjects included 160 patients suffering from esophageal varices complicated by liver cirrhosis without hepatocellular carcinoma. Sixty-eight patients underwent emergency therapy for bleeding varices and the remaining 92 patients underwent prophylactic sclerotherapy. All subjects continued to receive therapy until the varices disappeared. RESULTS: Five-year survival was significantly better in the prophylactic group compared with the emergency group. During the 5-year observation period, 20 of the 68 patients in the emergency group experienced rebleeding and 5 patients died as a result of rebleeding. These rates were significantly higher than those in the prophylactic group (1 of 9 patients with bleeding died among the 92 prophylactic sclerotherapy patients). Multivariate analysis showed that prophylactic therapy and Child's C hepatic function were significant factors for 5-year survival. CONCLUSIONS: Prophylactic sclerotherapy for esophageal varices might be more effective in prolonging longterm survival of patients complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy.

Adult↗