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61.
STUDY DESIGN: Prospective, multicenter, observational research study. BACKGROUND: Minimal research exists that describes the potential for serious gastrointestinal complications in individuals receiving outpatient physical therapy care. OBJECTIVE: To identify the prevalence of risk factors for gastrointestinal complications induced by anti-inflammatory drugs or aspirin in individuals receiving outpatient physical therapy services. METHODS AND MEASURES: A self-administered questionnaire was used at 65 ambulatory physical therapy clinics to document past medical history, history of present illness, and medication use. Risk factors for anti-inflammatory-drug- or aspirin-induced gastrointestinal complications were identified and the proportion of patients reporting each factor was determined. RESULTS: A total of 2433 patients completed the survey. Of the 2311 evaluable patients included in the study, 78.6% reported over-the-counter or prescribed use of an anti-inflammatory drug or aspirin during the week prior to the survey. Forty-nine percent of the patients reported at least 1 risk factor for drug-induced gastrointestinal complications, while 12.9% reported 2 or more risk factors. The most frequently reported established risk factors among anti-inflammatory drug or aspirin users were (1) combination (dual) therapy (22.3% reported concomitant use of anti-inflammatory and aspirin therapy), (2) advanced age (15.7% were over the age of 61 years), (3) history of peptic ulcer disease (7.8% had a history of peptic ulcer disease), and (4) significant systemic illness (6.8% reported having rheumatoid arthritis or heart disease). A frequently encountered risk factor combination was advanced age with a history of peptic ulcer disease (12.7%). CONCLUSIONS: Patients seen at physical therapy ambulatory clinics present with multiple risk factors for anti-inflammatory-drug- or aspirin-induced gastrointestinal complications and provide a potential opportunity for risk reduction by clinicians working in this environment. 相似文献
62.
Meek RM McLellan S Reilly J Crossan JF 《The Journal of hand surgery, European volume》2002,27(3):270-273
This study compared the rates of proliferation and apoptosis of cells within nodules of Dupuytren's disease and nodules from patients that had been injected preoperatively with steroid (Depo-Medrone). It also compared the effects of steroids in apoptosis in cultured Dupuytren's cells and control fibroblasts from palmar fascia and fascia lata. Steroids reduced the rate of fibroblast proliferation and increased the rate of apoptosis of both fibroblasts and inflammatory cells in Dupuytren's tissue. Steroids also produced apoptosis of cultured Dupuytren's cells but not of palmar fascia and fascia lata cells. 相似文献
63.
Pepels PP Meek J Wendelaar Bonga SE Balm PH 《The Journal of comparative neurology》2002,453(3):247-268
The recent characterization of the corticotropin-releasing hormone (CRH) prehormone of the fish tilapia (Oreochromis mossambicus) showed that more variation exists between vertebrate CRH amino acid sequences than recognized before. The present study investigates whether the deviating composition of tilapia CRH coincides with an atypical distribution of CRH in the brain. For this purpose we applied immunohistochemistry, as well as radioimmunoassay (RIA) quantification in brain slices. The results are plotted in a new atlas and reconstruction of the tilapia brain. The largest population of CRH-immunoreactive (ir) neurons is present in the lateral part of the ventral telencephalon (Vl). Approximately tenfold less CRH-ir neurons are observed in the preoptic and tuberal region. The CRH-ir neurons observed in the preoptic region are parvocellular and do not, or hardly, display arginine-vasotocin (AVT) immunoreactivity. CRH-ir neurons are also present in the glomerular layer of the olfactory bulb, in the periventricular layer of the optic tectum, and caudal to the glomerular nucleus. A very dense plexus of CRH-ir terminals is located in the most rostral part of the dorsal telencephalon. This region has not been described in other teleosts and is in the present study subdivided into the anterior part of the dorsal telencephalon (Da) and the anterior part of the laterodorsal telencephalon (Dla). High densities of CRH-ir terminals were observed in and around Vl, in the tuberal region, around the rostral part of the lateral recess, and in the caudal part of the vagal lobe. In the pituitary, CRH-ir terminals are concentrated in the neuro-intermediate lobe. Overall, the immunohistochemical and quantitative data correlated well, as the RIA CRH profile in serial 160-microm slices revealed four peaks, which corresponded with major ir-cell groups and terminal fields. Our results strongly suggest that the CRH-ir cells of Vl project to the rostro-dorsal telencephalon. Consequently, they may not be primarily involved in regulation of pituitary cell types but may subserve other functions. The presence of a CRH-containing Vl-Da/Dla projection seems to be restricted to the most modern group of teleosts, i.e., the Acanthopterygians. Further anatomic indications for non-pituitary-related functions of CRH are found in the vagal lobe and the optic tectum of tilapia. Although the low CRH content of the preoptic region reported here for tilapia may be typical for unstressed fish, the fact remains that remarkably few CRH-ir neurons are involved in regulating the pituitary. Overall, the CRH distribution in the brain of tilapia is more widespread than previously reported for other teleosts. 相似文献
64.
Functional recovery after transection of the sciatic nerve in adult rats is poor, probably because of abnormalities in reinnervation. Denervation and reinnervation patterns were studied morphologically in the lateral gastrocnemius (LGC), tibialis anterior (TA), and soleus (SOL) muscles for 21 weeks after nerve transection (motor endplates by acetylcholinesterase staining; nerves by silver impregnation). Motor endplates in the TA showed improving morphology with age, and, at 21 weeks, three-quarters of these were normal. Poorest recovery was observed in the SOL, as, at 21 weeks, only one-third of the motor endplates had a normal morphology. Polyneuronal innervation initially was more pronounced in the SOL, but, at 21 weeks, 10% of the motor endplates in all three muscles were still polyneuronally innervated. Our results indicate important differences in the reinnervation of these three hindleg muscles, and, even at 5 months, abnormalities were still present. These factors may in part explain the abnormal locomotion in rats as well as the limited recovery of function observed clinically in humans after nerve transection. 相似文献
65.
66.
Elizabeth Fox John M Maris Brigitte C Widemann Kysa Meek Anne Goodwin Wendy Goodspeed Marie Kromplewski Molly E Fouts Diane Medina Steve Y Cho Susan L Cohn Andrew Krivoshik Anne E Hagey Peter C Adamson Frank M Balis 《Clinical cancer research》2006,12(16):4882-4887
PURPOSE: To determine the toxicity profile, dose-limiting toxicities, and maximum tolerated dose of ABT-751 administered orally once daily for 7 days, repeated every 21 days. EXPERIMENTAL DESIGN: Patients who were =18 years of age, with relapsed or refractory solid tumors, and who were able to swallow capsules were eligible. The starting dose was 100 mg/m(2)/d (n = 3) and was escalated to 130 mg/m(2)/d (n = 6), 165 mg/m(2)/d (n = 6), 200 mg/m(2)/d (n = 6), and 250 mg/m(2)/d (n = 2) in cohorts of three to six patients. The maximum tolerated dose was determined from dose-limiting toxicities occurring during the first treatment cycle. RESULTS: Twenty-four children (median age, 13 years; range, 4-18 years) were enrolled; 23 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 8), sarcomas (n = 8), primary brain tumors (n = 2), Wilms' tumor (n = 2), and other solid tumors (n = 3). Dose-limiting toxicities (grade 3 sensory and motor neuropathy, grade 3 hypertension, and grade 3 fatigue) were observed in patients enrolled at the 250 mg/m(2)/d dose level. The maximum tolerated dose of ABT-751 administered daily for 7 days every 21 days was 200 mg/m(2)/d. Non-dose-limiting toxicities at the maximum tolerated dose included anemia, fatigue, peripheral sensory neuropathy, abdominal pain, nausea, constipation, anorexia, fever, and weight loss. Myelosuppression was minimal at the maximum tolerated dose. The median number of cycles administered is 2 (range, 1-50). No significant ABT-751-related cumulative toxicities were observed. CONCLUSION: ABT-751 is well tolerated in children. The recommended dose for phase 2 trials in solid tumors is 200 mg/m(2)/d administered orally, daily for 7 days every 21 days. This dose is >40% higher than the maximum tolerated dose in adults receiving the same dosing schedule. 相似文献
67.
Porter DW; Yakushiji H; Nakabeppu Y; Sekiguchi M; Fivash MJ Jr; Kasprzak KS 《Carcinogenesis》1997,18(9):1785-1791
The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in
cultured cells, has been associated with generation of the promutagenic
lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects.
One possible source of this base may be 8-oxo-7,8-
dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of
oxidative damage to the nucleotide pool, from which it is incorporated into
DNA. To promote such incorporation, the metals would have to inhibit
specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the
nucleotide pool. The present study was designed to test such inhibition in
vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein
and Escherichia coli MutT protein. In the presence of Mg(II), the natural
activator of 8-oxo-dGTPases, all four metals were found to inhibit both
enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 microM
for Cu(II), 30 +/- 8 microM for Cd(II), 376 +/- 71 microM for Co(II) and
801 +/- 97 microM for Ni(II). For MutT, they were 60 +/- 6 microM for
Cd(II), 102 +/- 8 microM for Cu(II), 1461 +/- 96 microM for Ni(II) and 8788
+/- 1003 microM for Co(II). Thus, Cu(II) and Cd(II) emerged as much
stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be
generally more sensitive to metal inhibition than MutT. Interestingly, in
the absence of Mg(II), the activity of the enzymes could be restored by
Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the
other metals being much less or non-effective. The difference in
sensitivity to metal inhibition between the two enzymes may reflect the
differences in the amino acid ligands, especially the cysteine ligand,
outside their evolutionarily conserved Mg(II)-binding active sites, which
might indicate predominantly non-competitive or uncompetitive mechanism of
the inhibition. The overall results suggest that inhibition of 8-oxo-
dGTPases may be involved in the mechanisms of induction of the 8-
oxoguanine lesion in DNA by the metal ions studied, especially the non-
redox-active Cd(II) cation.
相似文献
68.
A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas. 相似文献
69.
70.
Wagenaar M Draaijer P Meek H ten Donkelaar HJ Wesseling P Kimberling W Cremers C 《International journal of pediatric otorhinolaryngology》1999,50(3):185-195
Hypothesis: Does long-term sound deprivation lead to degeneration of the cochlear nuclei in two Usher type I patients? Methods: The cochlear nuclei of these patients were morphometrically analyzed and compared with two age-matched controls. Routine autopsy of the brainstems was performed before the design of this study was known. During this procedure, the ventral cochlear nucleus (VCN) can easily be damaged. Five partially damaged VCN could nevertheless be analyzed for this study, including the right VCN of Usher patient I and both VCN of Usher patient 2. Using 15 μm thick serial paraffine sections of the cochlear nuclei, estimates of volume, neuronal densities, number of cells and mean cell diameter of the dorsal cochlear nucleus (DCN) and VCN were obtained. Results: This study presents unique material of the cochlear nuclei in two patients with Usher syndrome type I. Data regarding volume and total cell number of the VCN are influenced by the absence of a part of the VCN. Results suggest a decrease in mean cell diameter of the VCN in Usher patients. Other parameters of the VCN and DCN, however, showed no major differences between Usher type I patients and controls. Conclusion: Only minor degenerative changes are apparent in the cochlear nuclei of two patients with Usher type I, who were deprived of acoustic stimuli since birth. 相似文献