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HUGH F. MOLLOY F.A.C.D. ERIC LAMONT-GREGORY M.SC. CHRIS IDZIKOWSKI PH.D. F.B.PS.S. TERENCE J. RYAN D.M. F.R.C.P. 《International journal of dermatology》1993,32(9):668-672
Background. Extensive questioning of patients with a wide variety of skin disorders led to the impression that nocturnal overheating was probably an important factor in the initiation and the perpetuation of many skin disorders. Methods. In order to test the hypothesis, 12 “clean-skinned” subjects (6M/6F) aged 18 to 45 years were monitored electronically every 30 seconds during an 8 hour sleep period (2300 to 0700 hours), sleeping under a standard 10 tog duvet. Results. All the subjects were too hot by 3 to 4°C. All showed changes in their EEG patterns with reduced REM sleep, increased awakenings, and all showed changes in their sleep stage patterns. In addition, they all showed evidence of increased sweating in the “heat-sink” area. Conclusions. The mechanisms where by such changes could be implicated in the precipitation and perpetuation of skin disease are discussed. “Lifestyle” modification as a very effective, noninvasive, therapeutic regime is recommended. Further research along these lines would probably be very valuable and instructive. 相似文献
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Myofibroblasts and the progression of diabetic nephropathy 总被引:23,自引:3,他引:20
Essawy M; Soylemezoglu O; Muchaneta-Kubara E; Shortland J; Brown C; El Nahas A 《Nephrology, dialysis, transplantation》1997,12(1):43-50
Background. The cellular mediators of progressive
renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have
been implicated in the pathogenesis of experimental and clinical renal
fibrosis. Their role in the progression of diabetic nephropathy is the
subject of this study.Subjects and methods. We have
studied by immunohistochemistry the expression of cytoskeletal proteins
associated with the activation of myofibroblasts; &agr;-smooth-muscle
actin (&agr;-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25
patients with diabetic nephropathy (5 patients with diabetic nephropathy (5
patients had a superimposed glomerulonephritis). Comparisons were made with
normal tissue for three kidneys removed for renal-cell carcinoma.
Correlations were studied between clinical and biochemical parameters with
the expression renal cytoskeletal proteins. Results.
In normal kidneys, cells expressing &agr;-SMA were confined to the
vascular media and adventia while immunoreactive Vi was detected in
glomerular epithelial cells. In diabetic kidneys, cells expressing
&agr;-SMA were detected primarily in the renal interstitium and to a
lesser extent in some glomeruli in association with mesangial
proliferation. Vimentin immunostain decreased in glomeruli displaying
diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity
was noted in atrophic diabetic tubules and to a lesser extent in the
interstitium. Desmin was not detected in either normal or diabetic kidneys.
Close correlations were observed between the expression of renal
cytoskeletal proteins and the progression of renal insufficiency.
Interstitial &agr;-SMA proved to be a predictor of progressive diabetic
nephropathy (R2 for 1/serum Cr slope=0.608,
P=0.00001). This predictive parameters; tubular atrophy
(R2=0.477, P=0.00004) and interstitial fibrosis
(R2=0.28, P=0.001). Conclusion.
We have demonstrated in this study the neoexpression of cytoskeletal
proteins within diabetic kidneys. This has allowed the identification of
new predicting histological markers for the progression of diabetic
nephropathy. 相似文献
5.
Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria. 总被引:6,自引:2,他引:4
Dimitrios S Goumenos Sotiris Tsakas Abdel Meguid El Nahas Sotiria Alexandri Simon Oldroyd Pantelitsa Kalliakmani John G Vlachojannis 《Nephrology, dialysis, transplantation》2002,17(12):2145-2152
BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1). METHODS: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion. RESULTS: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated. CONCLUSIONS: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production. 相似文献
6.
7.
G G Nahas 《Bulletin on narcotics》1990,42(1):57-62
Continuation of the practice of experimental administration of cocaine to cocaine-addicted volunteers has been recommended by some investigators. The author's view is that the risk of experimental use of cocaine outweighs its benefits and that this practice should not be pursued. The author describes the damaging effects of cocaine on the cardiovascular system, particularly its ability to induce myocardial band necrosis, and the unique reinforcing properties of the drug. The legal and ethical issues raised by the experimental use of cocaine are also discussed. 相似文献
8.
Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. 总被引:6,自引:0,他引:6
John P O'Reardon H Brent Solvason Philip G Janicak Shirlene Sampson Keith E Isenberg Ziad Nahas William M McDonald David Avery Paul B Fitzgerald Colleen Loo Mark A Demitrack Mark S George Harold A Sackeim 《Neuropsychopharmacology》2007,62(11):1208-1216
BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder. 相似文献
9.
Anderson RA; Evans LW; Irvine DS; McIntyre MA; Groome NP; Riley SC 《Human reproduction (Oxford, England)》1998,13(12):3319-3325
Follistatin is a binding protein for the activin and inhibin family of
hormones, regulating their biological activity. In the male reproductive
tract, the interaction of these factors is likely to be involved in the
regulation of the proliferation of several cell types. We have investigated
the presence of follistatin and activin A in seminal plasma using specific
immunoassays and have localized follistatin and activin/inhibin subunits in
the adult human testis, prostate and seminal vesicle to establish their
likely sources. High concentrations of immunoreactive follistatin were
present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in
peripheral plasma) and were similar in men with oligo/azoospermia and
following vasectomy. Follistatin immunoreactivity was localized to both
Leydig and Sertoli cells of the testis, and to epithelial cells of the
prostate gland and seminal vesicle, which are likely to be the predominant
sources of the hormone in seminal plasma. Activin A was also present in
seminal plasma in normal men but was undetectable following vasectomy, thus
deriving from the testis. Consistent with this finding, the betaA-subunit
was immunolocalized in Sertoli and Leydig cells but was not present in
seminal vesicle or prostate gland. The functional significance of the high
concentrations of follistatin secreted into seminal plasma by the prostate
gland and/or seminal vesicle is uncertain, but they may regulate the
biological activity of testis-derived activin A and inhibin B.
相似文献
10.
OBJECTIVE: The authors evaluate operative and extended outcomes of coronary artery bypass surgery using the bilateral internal thoracic arteries (ITAs) as bypass grafts. The authors conclude that the procedure is viable and of long-term benefit to most patients. SUMMARY BACKGROUND DATA: Multiple ITA grafting was met with early enthusiasm by the surgical profession, but skepticism and controversy arose with reports of increased operative morbidity, insufficient graft blood flow, a high incidence of failure of the right ITA, and uncertainty about durability and long-term benefits. METHODS: To assess the actual incidence and impact of these complications and long-term results, the authors prospectively studied 500 consecutive patients with multiple ITA bypasses, constituting the closely observed and carefully documented experience of one surgeon over an 11-year period. RESULTS: Operative mortality in the series of 500 patients was 1.8%, perioperative myocardial infarction (new Q wave) rate was 0.6%, and deep sternal wound infection occurred in 1%. Six patients (1.2%) had strokes, and nine patients (1.8%) were returned to the operating room to control bleeding. One hundred ninety-eight patients who had abnormal stress test results before surgery were retested within 3 months of surgery. Ninety-four percent of these were normal, 3% were nondiagnostic, and 3% were abnormal. After a mean follow-up of 7.1 years (mode, 7.2 years), 87.5% of patients in the sample were alive, and 93.2% of this group have experienced continuing good clinical results (New York Heart Association class I or II). Eighty-nine patients who underwent an angiogram had 90.8% patency rates of ITA bypasses and 84.5% patency of vein grafts. Only two patients required repeat operations. CONCLUSIONS: The operative results did not support the contention that the coronary artery bypass using ITA procedure produces higher than acceptable mortality and morbidity rates. Multiple ITA bypasses can be performed without excessive morbidity, with low reoperation rates and long-term outcomes that should encourage skeptics to reconsider the procedure's clinical value. 相似文献