Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX®. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications. 相似文献
The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors. 相似文献
Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa. 相似文献
We describe a case of 1:1 atrial flutter in a patient with coronary disease taking propafenone. In atrial flutter, the atrial rate is usually about 300 beciis/min with 2:1 AV conduction and a ventricular rate of 150 beats/min. Class IA antiarrhythmic drugs, especially quinidine and disopyramide, may cause 1:1 AV response because they reduce atrial rate and are vagolytic. However, propafenone is a Class IC agent and has no anticholinergic properties, and the occurrence of 1:1 AV conduction at a rate of about 250 beats/min is an important side, effect that, although uncommon, should be recognized. 相似文献
Purpose: To assess the accuracy of intraarterial measurement of transstenotic pressure gradients for the detection of hemodynamically
suboptimal iliac angioplasty.
Methods: In 14 patients, referred for diagnostic angiography, mean pressure gradients in the aorta and iliac artery were obtained
twice, using a double-sensor pressure catheter. Additional iliac measurements were performed during pharmacologically induced
flow augmentation. Repeatability was assessed by calculation of the mean difference plus standard deviation (MD ± SD) and
repeatability coefficient (2 × SD). These results were extrapolated to 137 iliac angioplasty procedures with secondary stenting
where there was a residual pressure gradient > 10 mmHg.
Results: MD ± SD for repeated measurements at rest and during flow augmentation were 0 ± 2 mmHg and 1 ± 3 mmHg, respectively. Repeatability
coefficients were 3 and 6 mmHg. Mean pressure gradients after hemodynamically insufficient angioplasty were 8 ± 7 mmHg at
rest and 17 ± 5 mmHg following vasodilatation. Inaccurate pressure recordings may have led to inappropriate stent placement
in less than 2.5%, and inappropriate denial of stent placement in less than 5% of the lesions.
Conclusion: Variability of intraarterial pressure measurements has little consequence in the detection of hemodynamically significant
stenosis after angioplasty.
Received: 0/00/00/Accepted: 0/00/00 相似文献
Acute renal failure (ARF) developed in a 7-week-old infant due to bilateral candidal bezoars (fungal balls) causing obstruction
at the pelviureteric junction. The baby was born at term with an appropriate birthweight, and had been treated with broad-spectrum
antibiotics for respiratory distress and septicemia during the 1st week of life. Recovery from ARF followed renal decompression
with bilateral nephrostomy tube placement and parenteral administration of amphotericin B and 5-flucytosine.
Received August 21, 1996; received in revised form and accepted January 3, 1997 相似文献
The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that Cmax and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.
The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.
The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey. 相似文献
. Neutrophil-mediated tissue damage has been implicated in the pathogenesis of diarrhoea-associated haemolytic uraemic syndrome
(D+ HUS). This study evaluates priming and activation of the neutrophil oxidative burst in D+ HUS using chemiluminescent techniques.
Peripheral blood neutrophils from 11 children with acute D+ HUS were examined. No difference was found in the oxidative burst
of neutrophils from patients and controls. Serum elastase levels were measured in 8 patients and found to be significantly
elevated. Although elastase results suggest neutrophil activation, chemiluminescence studies do not confirm this in the peripheral
blood neutrophil. This does not support a significant role for circulating agents in priming and activating the peripheral
blood neutrophil.
Received August 17, 1995; received in revised form and accepted November 27, 1995 相似文献