Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

133Granulation Tissue Induction by Lassar Ointment vs. Collagen‐Polyvynilpyrrolidone in Venous Ulcers

Venous leg ulcers derived from tissue destruction is the consequence of a chronic inflammatory process that produces pain and physical disability, diminishing quality of life in patients. In this work, Lassar ointment and lyophilized collagen‐polyvinylpyrrolidone were administered separated each on one half in the same ulcer to 9 patients at the beginning and every 4 days. On day 16, all patients were auto‐grafted with partial thickness skin. Granulation tissue and graft integration were assessed clinically during 3 months. Inflammatory infiltrate, type I and III collagens, elastic fibers, alkaline phosphatase as well as blood vessels were evaluated histologically or histochemically in biopsies taken at the beginning and 16 days after the local treatment. Clinically and morphologically, both treatments demonstrated appropriate granulation tissue promotion and optimal graft integration since the beginning. Nevertheless, in Lassar ointment treated group regionalization of alkaline phosphatase activity was observed, as well as the presence of granuloma in 2 of the 9 patients. In conclusion, Lassar ointment or lyophilized collagen‐polyvinylpyrrolidone are two different promoters of granulation tissue in venous leg ulcers, however Lassar ointment has the capability to produce granuloma and an exacerbated immune response; in consequence, ulcer recidivism could be present, may be due to mineral deposits in the wound.     

Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

The epidemiology and surveillance of blood lead in Taiwan (R.O.C.): A report on the PRESS-BLL project

 To monitor the lead hazards in industries and to investigate the prevalence of elevated blood lead levels (BLLs) in lead-exposed workers, a lead surveillance system (PRESS-BLLs) has been established and operated in Taiwan, Republic of China, since July 1993. A cohort of lead-exposed workers who received a periodic annual health examination at 55 accredited hospital laboratories was constructed. A total of 9807 separate BLL measurements were reported to the system in 1994. The mean BLL was 15.8 μg/dl in male workers and 11.6 μg/dl in female workers. The mean BLL of lead-exposed workers was significantly (P<0.05, z-test) higher than that of the general Taiwanese population (8.6 μg/dl for males and 6.7 μg/dl for females). In addition, the BLLs of 983 (10.0%) workers exceeded the regulatory action level (40 μg/dl for males; 30 μg/dl for females). The workplaces and homes of 57% of the workers with elevated BLLs were thoroughly investigated to determine the sources of lead contamination. These actions identified the causes of elevated BLLs and set up strategies to reduce workers’ lead exposure. The establishment of this occupational lead surveillance system represents a method for monitoring of lead hazards from occupational and environmental settings to prevent lead poisoning. The information acquired from the system can help in the setting up of a priority of prevention and the development of control measures. It is also useful for further monitoring of changes in the BLLs of the lead-exposed-worker cohort. The Health Department of Taiwan can use this information to evaluate the effectiveness of current industrial hygiene practice. Subjects with elevated BLLs have been medically treated and placed on long-term follow-up for sequelae. Received: 2 September 1996/Accepted: 29 November 1996     

Purification and chemical modification of porcine bone morphogenetic protein

Implantation of porcine bone morphogenetic protein (pBMP) in the muscle induces differentiation of mesenchymal-type cells and results in endochondral bone formation. pBMP was isolated from porcine demineralized bone matrix and purified by hydroxyapatite chromatography, Sephadex G75 gel filtration, preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), preparative isoelectric focusing (IEF), and chromatofocusing fast protein liquid chromatography (FPLC). Porcine BMP has an MW of 26 K and a range of pI from 4.65 to 4.73 determined by SDS-PAGE and IEF, respectively. Reconstitution with the citrate buffer supernatant fraction enables as little as 50 micrograms of the soluble pBMP fractions to induce osteogenesis in an in vivo assay. Chemical modification studies indicate that the osteoinductive potential of the pBMP molecule depends on tyrosine, carboxyl groups, and disulfide bonds and can be increased by modification of sulfhydryl groups. Modification of arginine and tryptophan has no effect on bioactivity. By pepsin-limited proteolysis, fragments of pBMP with an MW of 6-14 K show definite, although reduced, BMP activity.     

Selective intra-arterial methylene blue injection: a novel method of localizing gastrinoma.

A 40-year-old woman had persistent Zollinger-Ellison syndrome despite excision of a 4-cm duodenal gastrinoma. Localizing studies including ultrasonography, computed tomography, magnetic resonance imaging, duodenal endoscopy, endoscopic ultrasonography, and intraoperative endoscopic transillumination of the duodenum failed to detect a tumor. Selective intra-arterial methylene blue injection was used to identify a 6-mm gastrinoma in the duodenum, which was locally excised. Postoperatively, the patient had a negative secretin provocative test result. This novel method uses selective arterial secretin injection with hepatic venous gastrin sampling to identify the vessel feeding the gastrinoma. An angiographic catheter is then positioned in this artery. At laparotomy, methylene blue is injected through this catheter to selectively stain the gastrinoma, facilitating its identification. Selective intra-arterial methylene blue injection can enhance intraoperative detection of small gastrinomas and may improve the rate of curative resection in the Zollinger-Ellison syndrome. Further evaluation of this novel localizing technique is warranted.     

Effects of posts on dentin stress distribution in pulpless teeth.

A finite element analysis was carried out to study the roles of posts in reducing dentin stress in pulpless teeth. Two-dimensional plane strain models of the midlabiolingual section of a human maxillary central incisor were first analyzed. The results showed that the gold alloy post reduced maximal dentin stress by as much as 30%. However, the integrity of the dentin was compromised and the effects of the post were likely to be exaggerated in such models. In an effort to correct for these problems, plane stress models with side plates and axisymmetric models were analyzed. Posts were found to reduce maximal dentin stress by only 3% to 8% when the teeth were subjected to masticatory and traumatic loadings in these latter models. Although posts reduced maximal dentin stress by as much as 20% when the teeth were loaded vertically, teeth such as incisors and canines normally are not subjected to vertical loadings. Thus the reinforcement effects of posts seem to be doubtful in these teeth.     

Efficacy of short‐term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food‐cobalamin malabsorption: A study of 30 patients

Background: It has been suggested that oral cobalamin (vitamin B₁₂) therapy may be an effective therapy for treating cobalamin deficiencies related to food‐cobalamin malabsorption. However, the duration of this treatment was not determined. Patients and method: In an open‐label, nonplacebo study, we studied 30 patients with established cobalamin deficiency related to food‐cobalamin malabsorption, who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month. Endpoints: Blood counts, serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment. Results: During the first month of treatment, 87% of the patients normalized their serum cobalamin levels; 100% increased their serum cobalamin levels (mean increase, +167 pg/dl; P < 0.001 compared with baseline); 100% had evidence of medullary regeneration; 100% corrected their initial macrocytosis; and 54% corrected their anemia. All patients had increased hemoglobin levels (mean increase, +0.6 g/dl) and reticulocyte counts (mean increase, +35 × 10⁶/l) and decreased erythrocyte cell volume (mean decrease, 3 fl; all P < 0.05). Conclusion: Our findings suggest that crystalline cyanocobalamin, 250–1000 μg /day, given orally for 1 month, may be an effective treatment for cobalamin deficiencies not related to pernicious anemia.     

Restriction fragment length polymorphism analysis to study the genetic origin of complete hydatidiform mole.

To determine the genetic origin of the complete hydatidiform mole, 20 abnormal pregnancies were studied with restriction fragment length polymorphism with five genomic probes: EJ 6.6, beta-globin gene, 3'alpha-hypervariable region, J-Bir, and St14. In the 12 cases of molar pregnancy, pure paternal origin was proved in 11 cases, but both maternal and paternal inheritance were shown in only one case. In the cases with pure paternal origin, all of the restriction fragment length polymorphisms were homozygous, although those of the fathers were heterozygous at 15 loci. In the four cases that mimicked hydatidiform mole but were diagnosed as hydropic change of villi, both paternal and maternal inheritance were noted. In the four pregnancies with blighted ovum, both paternal and maternal inheritance were shown in three cases; and in one case with a balanced translocation between chromosomes 13 and 14, only paternal inheritance was noted. This study showed that most of the complete hydatidiform moles were caused by fertilization of an empty egg by a duplicated haploid sperm, but rare exceptions may exist.