Usefulness of the Pain-induced Functional Impairment Model to Relate Plasma Levels of Analgesics to Their Efficacy in Rats

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.     

Angiomyofibroblastoma-like tumors (cellular angiofibroma)

Angiomyofibroblastoma-like tumor (cellular angiofibroma) is a rare, circumscribed, slow-growing mesenchymal tumor that occurs predominantly in the vulva, perineum, and pelvis of women. We report two cases of this tumor in men arising as paratesticular masses of the scrotum, summarize the history of this tumor, and discuss why efforts should be made to differentiate it from aggressive angiomyxoma. Recommended treatment is complete surgical excision with long-term follow up exams, as local recurrence may occur many years after resection of the lesion.     

DERMATOFIBROSARCOMA PROTUBERANS

Background. Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive soft tissue sarcoma in which recurrences are common. It usually affects middle-aged individuals with the most common location being the trunk. Sex distribution varies among published series. Mohs surgery is the treatment of choice. Immunostaining for CD34 facilitates the diagnosis of DFSP and aids in indicating the surgical margins of the tumor; however, the sensitivity of this marker is variable. Materials and Methods. This is a retrospective review of 16 cases of DFSP treated with Mohs surgery at Duke University Medical Center between 1981 and 1994. Clinical and histologic features are analyzed. Immunohistochemical stains for CD34 were performed in one case. Results. Twelve of the 16 patients were women with four younger than 20 years. The most common location was the trunk. No recurrences following Mohs surgery have been documented. The average number of stages during Mohs surgery was 3.3. Surgical wounds were repaired by complex layered closure in 11 cases. Stains for CD34 were negative on the initial biopsy, but were positive on frozen sections. Conclusions. Both sexes and all age groups are affected by DFSP. Mohs surgery is the treatment of choice and offers a significant improvement in cure rates with the cosmetic advantage of smaller postoperative wounds. Immunostains for CD34 appear to be an important adjunct to facilitate tumor removal, but the variable expression of CD34 antigen by DFSP tumors can lead to variable staining patterns.     

MELANOCYTE RESERVOIR IN VITILIGO

Background. Dopa-negative, inactive melanocytes, present in the middle portion of the hair follicle, but also in hair bulbs, have been reported as a source of pigment cells, when repopulation of epidermal melanocytes occurs. A melanocyte reservoir in these anatomical sites has been suggested. Our objective was to investigate the ability of the lower third of the hair follicle (hair bulb) to repigment achromic skin in vitiligo. Methods. Scalp hair bulbs were transplanted within leukodermic areas in 10 patients with vitiligo. Results. Repigmentation around the grafts was suitable for evaluation in four cases. Dopa-positive (+) cells were seen in the epidermal basal cell layer of the repigmented areas. Conclusions. Although these findings were observed only in a few patients, they suggest that melanocytes from the implanted lower third portion of the hair follicle (hair bulb) act as a reservoir in this anatomic location and are able to migrate and repigment achromic areas in vitiligo.     

CB1 Cannabinoid Receptor-Dependent and -Independent Inhibition of Depolarization-Induced Calcium Influx in Oiigodendrocytes

Ca2+稳态平衡的调节在少突胶质细胞功能和存活中起重要作用.大麻素CB1和CB2受体在许多细胞中调节Ca2+水平和/或K+电流.本文利用培养的少突胶质细胞中,通过增高细胞外K+浓度(50 mM诱导膜去极化,研究大麻素复合物在此过程引发钙内流中的作用.CB2受体激动剂ACEA导致去极化诱导的少突胶质细胞胞浆的Ca2+瞬变表达浓度依赖性抑制,最大效应为(94±3)%,半效应浓度(EC50)为(1.3±0.03)μM.这种作用可被CB2/CB2激动剂CP55、940、内源性大麻素类AEA和2-AG所模拟,但是CB2受体选择性激动剂JWH133没有作用.CB2受体拮抗剂AM251(1μM)也可减少细胞外高K+诱导的Ca2+反应.但不能防止ACEA(3 μM)诱发的抑制效应.然而,ACEA和AEA减少去极化诱导的Ca2+瞬变的能力在CB2受体敲除小鼠和经百日咳毒素预处理的少突胶质细胞中明显降低.内流性K2+通道阻断剂BaCI:(300 μM)和CsCl2(1 mM)降低电压诱导的Ca2+内流并部分阻断ACEA的抑制效应.本文表明,大麻素抑制少突胶质细胞中去极化诱导的Ca2+瞬变是通过包括PTX-敏感的Gi/o蛋白和阻断K2+内流通道的CB2受体依赖性和非依赖性机制.     

Characterization of a Precocious New Lesion Distal to a Stent Site by Atherectomy

A 58-year-old woman presented with a new rapidly progressive lesion distal to a stent. This lesion was treated with atherectomy through the stem in order to characterize it pathologically. The aggressive proliferative response discovered suggested that this unusually distal lesion was produced by the trauma of her previous angioplasty .     

PLASMA INSULIN DISAPPEARANCE CURVE AFTER INTRAVENOUS INSULIN INJECTION IN HUMAN HYPERTHYROIDISM

The disappearance curves of plasma insulin after intravenous injection of unlabelled pork insulin was studied in nine young female hyperthyroid subjects with Graves' disease and eleven young female normal subjects, who served as controls. Comparison of the curves by analysis of variance did not reveal statistical differences between them (F obtained = 2.8, F F 0.05 = 4.41), implying that there was no significant differences in the transference of injected insulin from plasma to the extra-vascular space between hyper- and euthyroid subjects. The results may suggest that the metabolism of insulin is not appreciably affected in hyperthyroidism.     

What Can Be Expected of Balloon Aortic Valvuloplasty in Adults?

Introduced more than 15 years ago, balloon aortic valvuloplasty (BAV) has clearly delineated indications and limitations. Although, aortic valve replacement is undoubtedly the treatment of choice for healthy patients with aortic stenosis, BAV has been demonstrated as a valuable and safe palliative procedure for patients considered too risky or old for current day surgery. Between January 1991 and December 1999, 858 patients (mean age 76 ± 11 years, 479 [57%] women) underwent BAV at our center. Indications for BAV were contraindication to surgery in 16.2% of the patients, high risk in 40.4%, refusal of surgery in 10.7%, personal decision in 18.5%, and other in 14.2%. The mean gradient decreased from 65 ± 23 to 27 ± 12 mmHg and the valve area increased from 0.56 ± 0.19 cm² to 1.0 ± 0.38 cm². Eleven (1.1%) patients died during the procedure. The other severe complications were complete AV block in 18 (1.8%) patients, stroke in 8 (0.8%), tamponade in 6 (0.6%), and massive aortic insufficiency in 4 (0.4%). In conclusion, BAV does not replace valve replacement, even in the elderly. All those who can be operated on, should be. However, if surgical intervention is not considered reasonable, BAV offers good immediate results with an acceptable complication rate. Furthermore, previous published series have demonstrated that BAV is particularly indicated in specific subgroups, such as very old patients with high operative risk, end-stage heart failure, cardiogenic shock, or general anesthesia for noncardiac surgery.