Clinical evaluation of 0.5% ferric hyaluronate adhesion prevention gel for the reduction of adhesions following peritoneal cavity surgery: open-label pilot study

The objective of this study was to assess the safety and to make a preliminary assessment of the efficacy of 0.5% ferric hyaluronate adhesion prevention gel in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. The study was a randomized, open-label, placebo- controlled, parallel-group design in patients desirous of fertility at the Women's and Children's Hospital, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. Female patients aged 24 to 41 years received 300 ml 0.5% ferric hyaluronate adhesion prevention gel or lactated Ringer's solution as an intraperitoneal instillate at the completion of the laparotomy procedure. At second-look laparoscopy 4-12 weeks after the laparotomy, the presence of adhesions was evaluated. Haematology and serum chemistry were determined throughout the study interval. All patients tolerated the procedures well and did not manifest any serious adverse events. At second-look laparoscopy, patients treated with 0.5% ferric hyaluronate adhesion prevention gel had significantly fewer adhesions than control patients. When adhesions did form, they were significantly less extensive and less severe in patients who received 0.5% ferric hyaluronate adhesion prevention gel. In conclusion, 0.5% ferric hyaluronate adhesion prevention gel was safe and highly efficacious in the reduction of the number, severity and extent of adhesions throughout the entire abdomen following peritoneal cavity surgery.      

Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice

Missense mutations in the beta-amyloid precursor protein gene (APP) co- segregate with a small subset of autosomal dominant familial Alzheimer's disease (FAD) cases wherein deposition of the 39-43 amino acid beta-amyloid (A beta) peptide and neurodegeneration are principal neuropathological hallmarks. To accurately examine the effect of missense mutations on APP metabolism and A beta production in vivo, we have introduced yeast artificial chromosomes (YACs) containing the entire approximately 400 kbp human APP gene encoding APP harboring either the asparagine for lysine and leucine for methionine FAD substitution at codons 670 and 671 (APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon 717 (APP(V7171)) or a combination of both substitutions into transgenic mice. We demonstrate that, relative to YAC transgenic mice expressing wild-type APP, high levels of A beta peptides are detected in the brains of YAC transgenic mice expressing human APP(K670N/M671L) that is associated with a concomitant diminution in the levels of apha-secretase-generated soluble APP derivatives. Moreover, the levels of longer A beta peptides (species terminating at amino acids 42/43) are elevated in YAC transgenic mice expressing human APP(V7171). These mice should prove valuable for detailed analysis of the in vivo effects of the APP FAD mutations in a variety of tissues and throughout aging and for testing therapeutic agents that specifically alter APP metabolism and A beta production.      

Synthesis of viral proteins in polymorphonuclear leukocytes infected with influenza A virus.

Various reports have indicated that infection of polymorphonuclear leukocytes (PMNL) with influenza virus causes depression of their metabolic and chemotactic responses, but the effect the PMNL has on the life cycle of influenza virus has not been well defined. The studies reported here were undertaken to determine whether influenza virus could replicate within PMNL. Virus-infected and uninfected PMNL were labeled with [35S]methionine and analyzed by gel electrophoresis and fluorography for detection of newly synthesized proteins. Both host- and virus-specific proteins were produced within PMNL. By using indirect immunofluorescence techniques combined with flow cytometry, the expression of newly synthesized viral antigens was detected in virus-infected PMNL. Plaque assays on supernatant fluid from infected PMNL showed that infectious progeny were not produced, indicating that influenza virus infection of PMNL is abortive.     

Cloning of the capsid protein gene from a blotch isolate of peanut stripe virus

Summary The 3 terminal 1,367 nucleotides (nts) of a blotch isolate of the potyvirus, peanut stripe virus (PStV), were cloned and sequenced. This region included the 861 nts (287 amino acids) of the PStV capsid protein (CP). The amino acid sequence of the predicted proteinase cleavage site was identified. This region shared limited homology with other potyvirus proteinase cleavage sites. The viral CP gene sequence was followed by 254 nucleotides of 3 nontranslated sequence and a poly-A tail. Based on computer modeling, the 3 nontranslated region could form two lengthy stem-loop structures and two pseudoknot structures. Subclones containing the coding sequences of the CP (amino acids 1–287, 17–287, 17–113 and 106–287) were constructed and expressed inEscherichia coli. These polypeptides were detected using polyclonal antibodies in Western blots.     

Prader–Willi and Other Syndromes Associated with Obesity and Mental Retardation

Constitutional obesity and mental retardation cooccur in several multiple congenital anomaly syndromes, including Prader–Willi syndrome, Bardet–Biedl syndrome, Cohen syndrome, Albright hereditary osteodystrophy, and Borjeson–Forssman–Lehmann syndrome as well as some rarer disorders. Although hypothalamic–pituitary axis abnormalities are thought to be a possible causative mechanism in some of these disorders, current knowledge is insufficient to explain the pathophysiologic mechanism of obesity in most multiple congenital anomaly/mental retardation syndromes. The chromosomal location of many of these syndromes is known, and studies are ongoing to identify the causative genes. Further delineation of the functions of the underlying genes will likely be instructive regarding mechanisms of appetite, satiety, and obesity in the general population. This review details current knowledge of the clinical and molecular genetic findings of multiple congenital anomaly/mental retardation syndromes associated with intrinsic obesity in an effort to delineate causative mechanisms and genetic abnormalities contributing to obesity.     

Intravenous gamma globulin in the management of patients with hypogammaglobulinemia

The safety and efficacy of plasmin-treated gamma globulin (PG-GG), an intravenous preparation with low anticomplementary activity, was assessed as an antibody replacement therapy in 14 patients with hypogammaglobulinemia. Seven were studied in 2 treatment periods of 6 and 15 mo on PT-GG with an intervening control period of intramuscular gamma globulin (IM-ISG). Frequency of infusions ranged from 2 to 4 wk to maintain a serum IgG concentration of less than 2.5 mg/ml. Three patients with severe chronic pulmonary disease were removed from the study because of lack of clinical improvement and were placed on single-donor plasma. The remaining 11 patients had a decrease in the number of hospitalizations or severe infections. Five patients had one or more systemic reactions (21/240 infusions). Symptoms abated rapidly with temporary interruption of the infusion. From these results, we conclude that PT-GG represents a relatively safe, efficacious mode of replacement therapy which has had uniformly high acceptance in patients with hypogammaglobulinemia.     

The association of autoimmune diseases and anti-IgA antibodies in patients with selective IgA deficiency.

The prevalence of antibodies to immunoglobulin A (IgA) was studied in eighty-three subjects with selective IgA deficiency (SIgAD), thirty-three normal individuals, thirty-two children with juvenile rheumatoid arthritis (JRA) and normal or elevated IgA, seventeen children with systemic lupus erythematosus (SLE) and normal or elevated IgA, and thirteen patients with hypogammaglobulinaemia. Anti-IgA antibodies were detected by haemagglutination of human erythrocytes coated with one of two IgA myelomas by the chromic chloride technique. Antibodies to IgA were not found in significant titre in individuals with normal or elevated IgA or in those with hypogammaglobulinaemia. In IgA deficient patients, elevated titres were found in 25--30% of those who were healthy or who had non-rheumatic diseases, 50% of those with rheumatoid arthritis, 77% of those with JRA and 100% of those with SLE. Patients with rheumatic diseases and SIgAD may therefore be particularly at risk of developing anti-IgA-mediated reactions to blood products.