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Persistent hypouricemic effect of longterm diflunisal administration.

Diflunisal, a salicylic acid derivative, caused a significant fall in serum uric acid concentration from 0.29 +/- 0.02 to 0.20 +/- 0.02 mmol/l (mean +/- SEM) during chronic administration of 750 mg daily in 18 patients with rheumatoid arthritis. There was a significant correlation between plasma diflunisal concentration and fall of serum uric acid concentrations (p less than 0.01) at week 14. Diflunisal concentrations were statistically higher in females (p less than 0.05) at week 24.

Adult↗

Acute and long-term effects of 17 beta-oestradiol on agonist-stimulated force in rat tail artery.

The effects of 17 beta-oestradiol on the force responses to KCI and noradrenaline were investigated in rings of the rat tail artery. Incubation with 10 microM 17 beta-oestradiol for 100-295 min reduced the force amplitude after 5 min in high-K+ (140 mM) to 10% of the control value. The inhibitory effect of the steroid was unaffected by the NO-synthase inhibitor L-NAME. Rings activated by an intermediate degree of depolarization (60 mM K+) were less affected by the steroid (58% of control force). The sustained force response to 1 microM noradrenaline was reduced in the presence of 17 beta-oestradiol to 60% of control value. Lower concentrations of 17 beta-oestradiol (0.1 and 1 microM) were without acute effects on force development. However, longterm effects of 17 beta-oestradiol on vessel reactivity were found at these low concentrations. Rings were cultured for 3-7 days in the absence or in the presence of the steroid before they were stimulated with agonists. Cultured rings developed an increased sensitivity to noradrenaline compared with freshly prepared ones. Cocaine (30 microns) shifted the noradrenaline concentration-response curve to the left in freshly prepared rings while it had no effect in cultured ones, indicating that the increased sensitivity to noradrenaline in cultured rings depends on loss of noradrenaline uptake. Rings cultured for 7 days in the presence of 0.1 microM 17 beta-oestradiol developed a more pronounced supersensitivity to noradrenaline (EC50 for noradrenaline was 0.13 +/- 0.03 microM in steroid exposed rings vs. 0.38 +/- 0.09 microM in control rings). Thus, prolonged treatment with 17 beta-oestradiol results in a potentiation of noradrenaline evoked force, in contrast to the acute effect of the steroid.

Animals↗

Surgical approaches for improving the operating results of primary liver cancer.

The purpose of this study was to retrospectively analyse the results of 1102 primary liver cancer (PLC) patients who underwent liver resection in the past thirty years and to research some effective approaches for improving the longterm effect of PLC treatment. Ninety five percent were hepatocellular carcinoma (HCC), 85.2% with cirrhosis of hepatitis and 25.6% with tumor equal to or smaller than 5 cm in diameter. The mortality rate (MR) within 1 month after operation was 1.8%, the operative MR was 8.8% before 1977 and only 0.4% after that. The total 5-year survival rate (SR) was 28.4% while in the group of small tumor (less than or equal to 5 cm), it was 75.0%. Our experience is as follows: (1) Early diagnosis and early resection of PLC is the key point for improving the operative result of long-term survival. In 282 cases of small cancer, tumor resection rate was 90.0%. Of 48 cases with tumor equal to or smaller than 3 cm in diameter, the 5-year SR was 83.3%. (2) Rehepatectomy for recurrent liver cancer is an important approach for improving the surgical result. In our series, recurrent rate within 5 years postoperation was 72.3% in larger tumor group and 34.5% in small tumors. There were 78 cases undergoing reoperation in a total number of 170 times of rehepatectomy with 54.7% of 5-year SR, after the 1st operation and 34.6% after the 2nd one. (3) For unresectable large tumors, two-stage operation is an important development in liver surgery. We had 26 cases of such patients with 60.0% of 5-year SR. (4) Improvement of operating techniques plays an important role in reducing postoperative complications, lowering operative mortality and obtaining better operative result. (5) Postoperative comprehensive treatment is also important for solidating operative effect and preventing tumor recurrence.

Carcinoma, Hepatocellular↗

[The HIV protease inhibitor-induced insulin resistance syndrome].

BACKGROUND: HIV protease inhibitors improve the morbidity and mortality of HIV infection, however, this therapy also initiates insulin resistance that is associated with an increasing development of disturbances in glucose and lipid metabolism. Similar to the common insulin resistance syndrome, treated patients also suffer from an increased cardiovascular risk. PATHOGENESIS: Studies based on animal or cell models suggest that HIV protease inhibitors induce short-term effects on GLUT4 glucose transport and longterm effects on insulin signal transduction. CONCLUSION: Therapy with HIV protease inhibitors should include regular monitoring of metabolic alterations and cardiovascular damage. Particularly patients with genetic or traditional risk factors for type 2 diabetes should be monitored frequently.

Cardiovascular Diseases↗

Effects of mistletoe extract on murine thymocytes in vivo and on glucocorticoid-induced cell count reduction.

BACKGROUND: Mistletoe extracts are widely used in cancer patients due to their cytostatic and immunomodulatory effects. Essential components include mistletoe lectins which act as biomodulators with proinflammatory and apoptosisinducing effects. This study investigates the acute and longterm effects of standardized mistletoe extract (Iscador(R) M spec 5 mg) on thymocyte subpopulations and peripheral T-cells using a murine (Balb/c) model. MATERIALS AND METHODS: Using cell surface CD4/CD8 staining and flow cytometry, we followed the changes in CD4-CD8- double-negative (DN), CD4(+)CD8(+) double-positive (DP) and CD4(+) or CD8(+) single-positive (SP) T-cells 24 h after single or repeated injections of 3 different dilutions (1:12, 1:60, 1:300) corresponding to 2.1, 0.42 and 0.08 mg/kg of Iscador. Thymocyte apoptosis was detected by flow cytometry using Annexin V and propidium iodide. RESULTS: 24 h after a single injection of the 2 lower doses, the number of DN thymocytes increased significantly with an enhanced ratio of apoptotic cells. Following administration of the lowest dose, in peripheral blood the CD4(+)/CD8(+) ratio was elevated. In the long-term trial, Balb/c mice were treated twice a week with 3 different doses of Iscador +/- 20 mg/kg of dexamethasone (DX), resulting in significantly enhanced DN thymocytes and elevated levels of apoptotic cells after treatment with the 2 lower doses. Iscador also inhibited the DX-induced reduction in the thymic DN cell count, as well as the DX-induced decrease in the CD4(+)/CD8(+) ratio and CD4(+) in the peripheral blood. CONCLUSION: Our results suggest that standardized mistletoe extract modulates proliferation and apoptosis of thymocytes in a dose-dependent manner and may act lymphoprotective during DX treatment.

Animals↗

Effect of cyclosporine in rats with reduced renal mass.

The longterm effect of cyclosporine (CyA) on chronic renal failure was studied in female Wistar rats subjected to 4/5 to 5/6 nephrectomy by partial infarction of the left kidney followed by contralateral nephrectomy. CyA was added to a standard rat diet containing 25% protein. Each rat received 14 g of food daily containing 0 (control), 1.2 (group A), 2.4 (group B), or 4.8 (group C) mg CyA. The number of rats that did not survive the whole experimental period of 20 weeks on the CyA containing diets was similar to the control. In the surviving rats no difference between groups could be detected regarding body weight, serum creatinine and creatinine clearance. Proteinuria rose progressively up to 15 weeks in the control group and similarly in groups A and B. Mean proteinuria in group C was about half the control mean at 5-20 weeks. Systolic blood pressure differed little between groups A, B and control, but was significantly lower than control in group C at 10-20 weeks. Histologically groups B and C showed significantly less glomeruli with segmental sclerosis and less hypertensive vasculopathy than groups A and control. Histological signs of tubular CyA toxicity correlated with the doses applied: inclusion bodies were more frequent in all groups while the score of vacuolisation was increased significantly in group C only. In conclusion, CyA appears not to adversely affect or - at moderately toxic dosage - even to slow down progressive glomerular sclerosis in rats with reduced renal mass.

Animals↗

Adverse cardiovascular effects of ketamine infusion in patients with catecholamine-dependent heart failure.

The longterm effects of ketamine on haemodynamic parameters and exogenous catecholamine requirements were studied in twenty-five critically ill patients with catecholamine-dependent heart failure. Following sedation with midazolam (0.15 +/- 0.07, mg.kg-1.h-1) and sufentanil (0.88 +/- 0.33 microgram.kg-1.h-1), patients with impaired left ventricular function (left ventricular ejection fraction area 30 +/- 7%) were randomly assigned to receive ketamine (2.5 +/- 0.9 mg.kg-1.h-1) and midazolam (Group A) or remained on sufentanil/midazolam (Group B). Haemodynamic measurements were performed throughout the first 24 hours after randomization. In group A cardiac index decreased by 21% (P = 0.01), mean arterial pressure increased by 13% (P = 0.01), mean pulmonary artery pressure by 14% (P = 0.04), pulmonary capillary wedge pressure by 20% (P = 0.03), and systemic vascular resistance index by 38% (P < 0.001). No significant cardiovascular effects were observed in Group B. Neither group had significant changes of exogenous catecholamine requirement. In conclusion, ketamine exhibits potential negative cardiovascular effects in patients with catecholamine-dependent heart failure. Therefore, ketamine should not be considered a first line drug for longterm sedation of patients with impaired left ventricular function.

Aged↗

The treatment of osteoarthritis of the knee with pulsed electrical stimulation.

OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A multicenter, double blind, randomized, placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients' pain, patients' function, and physician global evaluation of patients' condition, and 6 secondary variables that included duration of morning stiffness, range of motion, knee tenderness, joint swelling, joint circumference, and walking time. Measurements were recorded at baseline and during the 4 week treatment period. RESULTS: Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment (p < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one primary efficacy variable in 50% of the active device group, in 2 variables in 32%, and in all 3 variables in 24%. In the placebo group improvement of > or = 50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group (p < 0.05). No statistically significant differences were observed for tenderness, swelling, or walking time. CONCLUSION: The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.

Adult↗

The variable effect of PEEP in acute respiratory failure associated with multiple trauma.

Both short and longterm effects of positive end-expiratory pressure (PEEP) on oxygenating capacity (OC) were investigated in three groups of patients with acute respiratory failure following multiple trauma (MT). Group A consisted of six patients with "uncomplicated" MT; Group B, eight patients with MT and generalized sepsis; Group C, nine patients with MT and lung contusion. OC was evaluated in terms of PaO2/FIO2 and P(A-a)DO2 on FIO 2 = 1.0. OC was markedly and equally reduced in the three patient groups before use of PEEP. The use of a mean PEEP of 6-7 cm H2O resulted in an initial improvement in mean PaO2/FIO2 of 152.5, 36.1, and 59.2 mm Hg, and an overall improvement of 196.8, 57.5, and 107.0 mm Hg in Groups A, B, and C, respectively. There was a similar improvement in both the initial and the overall effect of PEEP on P(A-a)DO2 in the three groups. The difference in the improvement in OC due to PEEP was statistically significant between Groups A and B. It is concluded that acute respiratory failure following MT includes a wide spectrum of clinical syndromes, and that the improvement in OCT due to PEEP depends on the clinical sydrome that is responsible for the respiratory failure associated with MT.

Acute Disease↗

[Regression of left heart hypertrophy in hypertensive patients as a result of antihypertensive therapy].

In a previous study (1) we could show a significantly more pronounced reversal of LVH with metoprolol than with gallopamil, whereas the combined therapy with atenolol and nifedipine was even more effective. We now report in 121 previously untreated hypertensive patients the longterm effect of the beta-blocker metoprolol (200 mg/die); 25 patients, mean age 43.6 yrs., follow-up 32.1 +/- 3.5 months, group A); the calcium antagonist gallopamil, 26 patients, mean age 49.7 yrs., follow-up 36.2 +/- 2.6 months, group B); the combined therapy with 50 mg atenolol and 20 mg nifedipine, 35 patients, mean age 44.5 yrs., follow-up 31.7 +/- 1.1 months, group C); 200 mg acebutolol and 20 mg nifedipine, mean age 52.1 yrs., follow-up 31.8 +/- 1.8 months, group D); 50 mg atenolol and 10 mg enalapril, mean age 43.3 yrs., follow-up 31.9 +/- 1.3 months, group E). Similar results were obtained for intraventricular septal and posterior wall thickness. Left ventricular enddiastolic dimensions remained unchanged but fractional shortenings were significantly (p less than 0.05-p less than 0.01) increased after 32 months of treatment.

Acebutolol↗

[Long-term effects of inpatient psychotherapy: explanatory and transfer forms of the psychotherapy experience into everyday life].

We describe the longterm effects of inpatient psychotherapy based on biographic interviews with 46 ex-patients two years after their treatment in a psychotherapy ward which is part of a psychiatric hospital. The concept of the treatment is based on cognitive behavior therapy. In a structural hermeneutic analysis of the interviews we found 4 different types of dealing with the experience of psychic disorder and psychological treatment and, combined with it, transfer of the knowledge about psychological disorder and treatment into everyday life: 1 the "development"-type-psychotherapy as a method to reframe the individual development. 2 the "deficit"-type-psychotherapy as a system to learn how to deal with individual deficits, 3 the "deviance"-type-psychotherapy as an instrument to renormalize deviation, 4 the "overburden"-type-psychotherapy as a private area to recover and regenerate.

Adaptation, Psychological↗

[Treatment of cholestatic liver diseases; the role of ursodeoxycholic acid].

Ursodeoxycholic acid (UDCA) allows symptomatic treatment of cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic biliary atresia, and cholestasis of cystic fibrosis. Patients should be treated at an early stage of the disease in order to prevent progression to cirrhosis. Since UDCA has no toxic effects longterm treatment with this substance is possible without the risk of undesired side effects. In patients with primary biliary cirrhosis and rapid progression of the disease, UDCA may be combined with an immunosuppressive substance (i.e. cyclosporin). In primary sclerosing cholangitis, biliary atresia and cholestasis of cystic fibrosis, UDCA at present seems the only treatment of which a benefit for the patients can be expected. In endstage disease liver transplantation is indicated. The role of UDCA in chronic hepatitis and alcohol induced liver disease needs to be clarified in further studies. Whether the improvement of laboratory tests in such patients indicates amelioration of the course of disease, still is unclear.

Animals↗

Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To investigate the longterm effects of the anti-tumor necrosis factor (TNF) therapy infliximab, a drug known to reduce disease activity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Eighty-two patients (50 with RA, 32 with AS) aged 17-77 years were enrolled. All patients were treated with intravenous infliximab. Lipid profile was assessed at baseline and after 6 months of treatment. RESULTS: Disease activity significantly decreased in patients with RA and AS at the end of infliximab therapy. Infliximab treatment significantly increased total cholesterol from 206 to 216 mg/dl (p < 0.05) and triglycerides from 109 to 122 mg/dl (p < 0.05). The low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol did not change during treatment. Furthermore, the total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios did not change significantly. CONCLUSION: The influence of infliximab treatment on lipid profile seems to be neutral, since neither LDL cholesterol levels nor total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios changed significantly during the 6-month therapy. Our findings suggest that the favorable effect of infliximab treatment on cardiovascular comorbidity may not be mainly mediated by the effects on the lipid profile, but further investigations are needed in order to confirm this hypothesis.

Adult↗

Longterm maintenance therapy with disease modifying antirheumatic drugs.

Longterm safety and efficacy of disease modifying antirheumatic drugs (DMARD) have been challenging to assess. There are few studies that have evaluated patient outcome beyond 5 years. As patients may receive several DMARD over the course of their disease a long with nonsteroidal antiinflammatory drugs, corticosteroids, and other drugs for comorbidities, it is difficult to design and implement a trial to define a specific drug's longterm effect. Based on the findings of several key studies, however, it does appear that DMARD are safe when taken longterm, and that they are more likely to be discontinued because of inefficacy than toxicity. Although DMARD are often discontinued because of lack of efficacy, 12 year data suggest that DMARD can provide benefit over this period. The toxicity profiles vary significantly between DMARD. In addition, the time during therapy when the majority of these adverse effects most frequently appear is DMARD-specific. Prospective studies are needed to further clarify longterm safety and efficacy of the newer DMARD.

Adult↗

[Effects of early rehabilitative treatment on neurological development and cognitive and perceptual-motor functions of preterm infants at risk].

Longterm effects of early rehabilitative treatment are evaluated in 37 premature infants at neurological risk. The late neurological and psychomotor development of this group of children (experimental group) is compared with that of another 35 at risk premature infants (control group), who received only conventional follow-up care. The two groups do not differ in birth-weight, gestational age, sex and neonatal disorders. At 6 years of age the children of the experimental group have a significantly better neurological status and score higher than the control group, on mean mental indices. They also have lower incidence of neurodevelopmental sequelae (learning disabilities and behaviour problems). However children both in the experimental group and the control group have poor visual-motor integration. Similar results are found also in children, who were low-risk premature infants and who have normal intelligence. Our data suggest that a prescribed early rehabilitative treatment for high-risk preterm infants appears enhance the quality of late development. Treated children have the greatest improvement in all measured outcomes at 6 years (included neurological status, motor and overall development), but do not achieve the same level of neurological and behavioral development as full-term control children. One might question whether the latter finding indicate limited efficacy of early treatment or rather the need to consider separate series of norms for the preterm infant in assessing its outcome. This question requires additional follow-up studies.

Child↗

[Athletic training of children and adolescents: growth and maturation more important than training for endurance in the young].

The effects of physical training in children differ from those in adults. The study of longterm effects is hampered by the lack of standardised criteria of growth in size and strength, and the standard variables usually adopted (percentage change in weight or body surface area) are as artificial as the absolute values. A review of available evidence suggests the effects of training on aerobic and anaerobic capacity, muscle strength, and flexibility to be limited before puberty, to be impossible to measure during the physical development of pubescence, and not to yield manifest benefit until after puberty. In contrast, prepubescent training of technique and motor skills yields lasting benefits, whereas--as with adults--the benefits derived from training of condition and strength rapidly disappear if not continually maintained.

Adolescent↗

Kinesthetic stimulation for preventing apnea in preterm infants.

BACKGROUND: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia, which may be severe enough to require resuscitation including use of positive pressure ventilation or other treatments. Physical stimulation is often used to restart breathing and it is possible that repeated stimulation, such as with an oscillating mattress (kinesthetic stimulation), might prevent apnea and its consequences. OBJECTIVES: In preterm infants at risk for apnea, does prophylactic use of kinesthetic stimulation lead to a clinically important reduction in apnea and bradycardia, and use of intemittent positive preswsure ventilation (IPPV). SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. SELECTION CRITERIA: All trials in preterm infants at risk of developing clinical apnea which utilised random or quasi-random allocation to treatment with an oscillating mattress or control, were eligible. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used with separate evaluation of trial quality and data extraction by each author and synthesis of the data using relative risk. MAIN RESULTS: There were no differences in short term effects (apnea /bradycardia, IVH, use of IPPV, sleep/wake cycles and neurological status at discharge) or longterm effects (in one trial - growth and development to one year). REVIEWER'S CONCLUSIONS: Implications for practice. Prophylactic use of kinesthetic stimulation cannot be recommended to reduce apnea/bradycardia in preterm infants. Implications for research. There are currently no clear research questions regarding prophylactic use of kinesthetic stimulation to prevent apnea in preterm infants.

Apnea↗