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.     

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.     

Therapeutic challenges in hepatitis C-infected injection drug using patients

Hepatitis C Viral (HCV) infection in the injection drug user (IDU) population is a major medical concern. Concurrent substance abuse, co-morbid mental health conditions, poor socioeconomic status and a complex treatment protocol that is often incompatible with the life styles of IDUs combine to account for poor uptake and completion of HCV treatment. This article discusses HCV antiviral treatment issues relevant to IDUs chronically infected with this virus. The effect of non-injected substances of abuse on treatment outcome is considered. Priority issues requiring research are discussed.     

Positive clinical impressions: II. Participants' evaluations

Nine months after the residential stage of Koach, participants were asked to evaluate the program's effectiveness. Most of the veterans reported improvement in the areas queried, and especially in social relations, and nearly all of them stated that they would recommend the program to other veterans. The commander-therapists became the major source of help for these veterans following the Koach project, and about half reported that they participated regularly in self-help groups. Most of the participants acquired coping techniques that continued to serve them 9 months after the end of the residential stage of Koach. One of the more important measures of Koach was thought to be the veterans' own evaluations of the project, their assessment of the project's success in achieving its aims, and their satisfaction with it. In this article we will present the subjects' evaluations of treatment effectiveness as expressed in behavioral and emotional changes that they attributed to the treatment.     

Failure of intensive chemotherapy in poor prognosis non-Hodgkin's lymphoma

In an attempt to improve response and survival rates in patients with non-Hodgkin's lymphoma, a relatively intense six drug regimen MATCOP was developed comprising four-weekly cycles of methotrexate (100mg/m², IV_Y day 8), Adriamycin (30mg/m², IV_Y days 1,2), teniposide (75 mg/rn², IV, day 1), cyclophophamide (300 mg/m², po, days one to five), Oncovin (1.4 mg/m², IV: maximum 2 mg, days 8,15) and prednisolone (100 mg, po, days one to five). A randomised trial was conducted comparing MATCOP with the standard CHOP regimen, comprising three-weekly cycles of cyclophosphamide (750 mg/m², IV, day 1), Adriamycin (50 mg/m², IV, day 1), Oncovin (1.4 mg/m² IV: maximum 2 mg, day 1) and prednisolone (100 mg, PO, days two to six). Eighty patients with large cell lymphoma, diffuse mixed small cleaved and large cell lymphoma or diffuse small cleaved cell lymphoma were randomised, 47 to MATCOP and 33 to CHOP. MATCOP patients experienced increased granulocytopenia, thrombocytopenia (p 0.0001), mucositis (p= 0.002) and infections (p= 0.01) compared to CHOP patients. Complete response rates were similar: 66% for MATCOP patients and 61% for CHOP patients. There were no apparent differences in the time to relapse for patients achieving CR, the time to treatment failure or the overall survival time. Thus despite an increase in toxicity, the more intense regimen MATCOP failed to confer any therapeutic benefit compared with the standard CHOP regimen. Survival was not influenced but toxicity was increased by dose intensification. (Aust NZ J Med 1992; 22: 123–128.)