Fibrosarcomatous change in dermatofibrosarcoma protuberans

This report describes six patients with dermatofibrosarcoma protuberans (DFSP) that contained fibrosarcomatous areas (FS). The clinical signs and symptoms, ages of the patients, and anatomic distribution of the tumors were similar to those of uncomplicated DFSP. FS was concentrated in the subcutis in each case and comprised more than 50% of the tumor in four cases. The characteristic storiform cellular arrangement of DFSP was replaced by long, gently sweeping fascicles of spindle cells that intersected at various angles, forming the so-called herringbone pattern. Trapped fat cells, characteristic of DFSP when it infiltrates subcutaneous tissue, were absent in five of the six FS and only focally present in one. Two FS were grade 1; their cytologic features were similar to those of DFSP. Four FS were grade 2 and had cytologic atypia exceeding that of DFSP. There was a statistical difference between the mitotic rates of DFSP and FS. Five patients were alive and well at the time of last follow-up (median, 2 years), and one patient had an unexcised recurrence when last examined. Six similar cases from the literature are reviewed; in one of them, the FS metastasized.     

Ct detection of cerebral metastases inapparent on magnetic resonance imaging scan

We report a case of malignant melanoma, metastatic to the brain, in which disease was not detected by magnetic resonance imaging but was detected by contrast enhanced computed tomography. At least in some instances, magnetic resonance imaging fails to detect disease that is apparent by computed tomography.     

Nemaline myopathy of cats

An apparently inherited myopathy, characterized by the presence of large numbers of nemaline rods in skeletal muscle fibers, was investigated in five cats. Onset of signs varied from 6 months to 1.5 years of age and consisted of reluctance to move, jerky gait and muscle twitching, hyporeflexia, and muscle wasting, which was most prominent in the proximal muscles of the forelimbs. All of the cats, three males and two females, were from the same dam. In addition to the presence of rods, the myopathy was characterized by marked fiber size variation, with atrophy of type 1 and type 2a muscle fibers. In addition, there was infolding of the sarcolemma and fiber splitting. Ultrastructurally, the rods closely resembled those described in human nemaline myopathy.     

Safety and effect of transforming growth factor-β2 for treatment of venous stasis ulcers

Transforming growth factor-beta(2) promotes healing in a variety of animal models and exhibits clinical effects thought to be mediated by connective tissue formation. Two clinical trials were conducted to evaluate the safety and effect of transforming growth factor-beta(2) purified from bovine bone and delivered topically to venous stasis ulcers three times per week for up to 6 weeks by means of a lyophilized collagen vehicle. The first was an open-label trial comparing transforming growth factor-beta(2) purified from bovine bone (0.5 microg/cm(2)) with a placebo consisting of lyophilized collagen vehicle-without active drug. After no safety issues arose in that trial, a prospectively randomized, closed-label, observer-blinded, three-armed trial was conducted to compare bovine transforming growth factor-beta(2) (2.5 microg/cm(2)) with the collagen matrix placebo vehicle and with a standard dressing. Standardized elastic compression was applied to all test extremities. The rate of reduction of ulcer area as measured by planimetry was the primary measure of effect. No serious safety-related events occurred in either trial. Clinical evaluation suggested that improvement in the quality and quantity of granulation tissue appeared to precede epithelialization of ulcers treated with bovine transforming growth factor-beta(2). In both studies, treatment with bovine transforming growth factor-beta(2) appeared to have a positive effect on the rate of ulcer closure, whereas ulcers in the control groups continued to exhibit impaired healing. In the open-label study, the mean rate of closure of ulcers treated with bovine transforming growth factor-beta(2) was significantly greater than that of ulcers treated with placebo. There was likewise enhanced reduction in ulcer area in the ulcers treated with bovine transforming growth factor-beta(2) in the second trial. However, because of a higher variability in patient response and a greater placebo effect, the difference was not significant. The placebo was not worse than the standard care arm, thereby showing that the vehicle is not injurious to healing. The combined results of the two trials suggest that, at doses of 0.5 to 2.5 microg/cm(2), bovine transforming growth factor-beta(2) is safe as a topically applied agent in a collagen matrix vehicle and can have a positive effect on closure of venous stasis ulcers. Large multicenter trials appear to be indicated to evaluate fully the potential utility of transforming growth factor-beta(2) in accelerating closure of chronic dermal ulcers.     

Corticotrophin-releasing factor immunostaining is present in placenta and fetal membranes from the first trimester onwards and is not affected by labour or administration of mifepristone

BACKGROUND AND OBJECTIVES Corticotrophin releasing factor (CRF) is present in the human placenta and fetal membranes. Placental CRF content and plasma CRF concentrations rise throughout gestation and fail rapidly after delivery. The regulation of CRF production from the placenta is poorly understood. The objective of this study was to use the antiprogestin, mifepristone, to determine whether progesterone has a regulatory effect on CRF production in the first trimester of pregnancy. PATIENTS Women undergoing first trimester (gestation 5-12 weeks) therapeutic abortion (by suction curettage with and without the synthetic PGE, analogue, gemeprost (16,16-dimethyl-trans- Δ²-PGE₁ methyl ester) vaginally 2-4 hours prior to the procedure; or with 600 mg mifepristone 48 hours prior to receiving 1 mg gemeprost vaginally), second trimester therapeutic abortion (600 mg mifepristone, 1 mg gemeprost), In association with pre-term delivery (gestation 25-34 weeks) and at term (gestation 35-42 weeks) by spontaneous delivery, induced labour or elective Caesarean section. MEASUREMENTS immunohistochemical localization Of CRF and quantification of CRF content by radioimmunoassay of tissue extracts, in human placenta and fetal membranes. RESULTS CRF was Immunolocalized to the syncytlo-trophoblast cells of the placenta at ail stages of gestation from 5 to 42 weeks. In the fetal membranes CRF immunoreactlvity was localized in the epithelial and subepithelial cells of the amnion, some cells of the reticular and cellular layers of the chorion, and in decidual stroma. This pattern was seen in all tissues studied. Pretreatment with prostaglandins, mifepristone or both during the first trimester did not alter the distribution or the intensity of the CRF Immunostaining. Placental CRF content rose throughout gestation but, consistent with the Lmmunostaining results, was unaffected by the administration of mifepristone or by labour. CONCLUSIONS CRF is localized in the syncitlotropho-blast cells of the placenta and is clearly present early in the first trimester of pregnancy. The lack of an effect of mifepristone or mode of delivery suggests that syncytlo-trophoblast produces CRF constitutively throughout pregnancy.     

Effects of Ethanol on Human Natural Killer Cell Activity: In Vitro and Acute, Low-Dose In Vivo Studies

Chronic use of ethanol may cause a variety of immunological abnormalities in humans. In this study, we have determined the effects of an acute, low dose of ethanol (0.5 g/kg), administered either intravenously or orally, to normal, nonalcoholic male volunteers, on natural killer cell (NK) activity. We have also examined the effects of a 4-hr incubation with ethanol, in concentrations ranging from 0 to 320 mg/dl, on human NK activity in vitro. NK activity was measured by the ⁵¹Cr release assay technique in all of these studies, using peripheral blood mononuclear cells prepared from blood obtained from healthy, nonalcoholic volunteers. Eight subjects received ethanol in vivo; cells from nine subjects were used for the in vitro studies. Blood ethanol concentrations were determined at multiple time points before and after ethanol administration for the in vivo studies; for the in vitro studies, ethanol concentrations were measured from each assay sample both before and after the incubation period. Gas chromatography was used for determinations of both blood alcohol and medium ethanol concentrations. Results of the in vivo studies showed that a single dose of ethanol (0.5 g/kg), administered either intravenously (with resultant peak blood levels transiently up to 89 mg/dl) or orally (with resultant peak blood levels transiently up to 40 mg/dl at the time of the NK assay), did not alter NK activity. However, results of the in vitro studies showed a significant dose-dependent decrease ( p < 0.001) in NK activity when ethanol exposure was sustained for 4 hr at concentrations of 80 mg/ dl and above. We conclude that one of the possible causes for a higher incidence of certain viral infections and malignant tumors among chronic alcoholics may be due, in part, to this observed direct effect of ethanol on NK cytotoxicity.     

Biostability and blood-contacting properties of sulfonate grafted polyurethane and Biomer.

Sulfonate-containing polyurethanes were evaluated for in vivo biodegradation using subcutaneously implanted tensile bars. In addition, these anionically charged polyurethanes were evaluated for in vivo activation of human complement C3a and ex vivo platelet deposition in arteriovenously-shunted canines. The sulfonate derivatized polymers included laboratory synthesized polyurethane and Biomer. Other polymers used for references included Intramedic polyethylene, Silastic and a poly(ethylene oxide) based polyurethane. The biodegradation results indicated that Biomer and the laboratory sulfonated Biomer (both manufactured with stabilizers), remained mechanically stable, retaining both tensile strength and elasticity after 4 weeks of subcutaneous implantation. The unstabilized polyurethanes (with or without sulfonation), however, showed marked cracking and a loss of mechanical properties after the same period of subcutaneous implantation. Sulfonated polyurethanes depressed human complement C3a activation in plasma, as indicated by decreased levels of anaphylatoxin production. The results of canine ex vivo blood contacting experiments were conducted in both an acute and chronic model and demonstrated decreased platelet deposition and activation for the sulfonated polyurethanes.     

Anticoagulant effects of sulphonated polyurethanes.

Sulphonated polyurethanes have been shown to have excellent blood contacting properties. In this paper, similar polyurethanes which are water soluble have been investigated to determine their influence on thrombus formation. These polymers were shown to delay clotting times in the following ways: by direct complex formation between the polymer and thrombin; by interference with fibrin polymerization; and by complex interactions between polymer, thrombin, plasma antiproteases and fibrinogen in plasma.